Tag Archives: Epidemiology

Perfect ‘pathogen’ storm: Vibrio bacteria, Sargassum and plastic marine debris

A new study uncovers how the interplay between Sargassum spp., plastic marine debris and Vibrio bacteria creates the perfect “pathogen” storm that has implications for both marine life and public health. Vibrio bacteria are found in waters around the world and are the dominant cause of death in humans from the marine environment. For example, Vibrio vulnificus, sometimes referred to as flesh-eating bacteria, can cause life-threatening foodborne illnesses from seafood consumption as well as disease and death from open wound infections.

Since 2011, Sargassum, free-living populations of brown macroalga, have been rapidly expanding in the Sargasso Sea and other parts of the open ocean such as the Great Atlantic Sargassum Belt, including frequent and unprecedented seaweed accumulation events on beaches. Plastic marine debris, first found in surface waters of the Sargasso Sea, has become a worldwide concern, and is known to persist decades longer than natural substrates in the marine environment.

Currently, little is known about the ecological relationship of vibrios with Sargassum. Moreover, genomic and metagenomic evidence has been lacking as to whether vibrios colonizing plastic marine debris and Sargassum could potentially infect humans. As summer kicks into high gear and efforts are underway to find innovative solutions to repurpose Sargassum, could these substrates pose a triple threat to public health?

Researchers from Florida Atlantic University and collaborators fully sequenced the genomes of 16 Vibrio cultivars isolated from eel larvae, plastic marine debris, Sargassum, and seawater samples collected from the Caribbean and Sargasso seas of the North Atlantic Ocean. What they discovered is Vibrio pathogens have the unique ability to “stick” to microplastics and that these microbes might just be adapting to plastic.

“Plastic is a new element that’s been introduced into marine environments and has only been around for about 50 years,” said Tracy Mincer, Ph.D., corresponding lead author and an assistant professor of biology at FAU’s Harbor Branch Oceanographic Institute and Harriet L. Wilkes Honors College. “Our lab work showed that these Vibrio are extremely aggressive and can seek out and stick to plastic within minutes. We also found that there are attachment factors that microbes use to stick to plastics, and it is the same kind of mechanism that pathogens use.”

The study, published in the journal Water Research, illustrates that open ocean vibrios represent an up to now undescribed group of microbes, some representing potential new species, possessing a blend of pathogenic and low nutrient acquisition genes, reflecting their pelagic habitat and the substrates and hosts they colonize. Utilizing metagenome-assembled genome (MAG), this study represents the first Vibrio spp. genome assembled from plastic debris.

The study highlighted vertebrate pathogen genes closely related to cholera and non-cholera bacterial strains. Phenotype testing of cultivars confirmed rapid biofilm formation, hemolytic and lipophospholytic activities, consistent with pathogenic potential.

Researchers also discovered that zonula occludens toxin or “zot” genes, first described in Vibrio cholerae, which is a secreted toxin that increases intestinal permeability, were some of the most highly retained and selected genes in the vibrios they found. These vibrios appear to be getting in through the gut, getting stuck in the intestines and infecting that way.

“Another interesting thing we discovered is a set of genes called ‘zot’ genes, which causes leaky gut syndrome,” said Mincer. “For instance, if a fish eats a piece of plastic and gets infected by this Vibrio, which then results in a leaky gut and diarrhea, it’s going to release waste nutrients such nitrogen and phosphate that could stimulate Sargassum growth and other surrounding organisms.”

Findings show some Vibrio spp. in this environment have an ‘omnivorous’ lifestyle targeting both plant and animal hosts in combination with an ability to persist in oligotrophic conditions. With increased human-Sargassum-plastic marine debris interactions, associated microbial flora of these substrates could harbor potent opportunistic pathogens. Importantly, some cultivation-based data show beached Sargassum appear to harbor high amounts of Vibrio bacteria.

“I don’t think at this point, anyone has really considered these microbes and their capability to cause infections,” said Mincer. “We really want to make the public aware of these associated risks. In particular, caution should be exercised regarding the harvest and processing of Sargassum biomass until the risks are explored more thoroughly.”

Study co-authors represent the NIOZ Royal Netherlands Institute for Sea Research, the Japan Agency for Marine-Earth Science and Technology, the Ludwig Maximilian University of Munich, Germany, Emory University, the University of Amsterdam and the Marine Biological Laboratory.

This research was supported by the National Science Foundation (NSF) (grant OCE-1155671 awarded to Mincer), FAU World Class Faculty and Scholar Program (awarded to Mincer), NSF (grant OCE-1155571 awarded to Linda A. Amaral-Zettler, Ph.D., corresponding author, NIOZ), NSF (grant OCE-1155379 awarded to Erik R. Zettler, Ph.D., co-author, NIOZ), NSF TUES grant (DUE-1043468 awarded to Linda Zettler and Erik Zettler).

  • Tracy J. Mincer, Ryan P. Bos, Erik R. Zettler, Shiye Zhao, Alejandro A. Asbun, William D. Orsi, Vincent S. Guzzetta, Linda A. Amaral-Zettler. “Sargasso Sea Vibrio bacteria: underexplored potential pathovars in a perturbed habitat”. Water Research, 2023; 120033 DOI: 10.1016/j.watres.2023.120033
  • Florida Atlantic University

    New compound with antibacterial activity shows promising results within one hour in laboratory trials

    Resistance to antibiotics is a problem that alarms the medical and scientific community. Bacteria resistant to three different classes of antibiotics, known as multi-drug resistant (MDR) bacteria, are far from rare. Some are even resistant to all currently available treatments and are known as pan-drug resistant (PDR). They are associated with dangerous infections and listed by the World Health Organization (WHO) as priority pathogens for drug development with maximum urgency.

    An article published in a special issue of the journal Antibiotics highlights a compound with antibacterial activity that presented promising results within one hour in laboratory trials.

    The study was led by Ilana Camargo, last author of the article, and conducted during the doctoral research of first author Gabriela Righetto at the Molecular Epidemiology and Microbiology Laboratory (LEMiMo) of the University of São Paulo’s São Carlos Institute of Physics (IFSC-USP) in Brazil.

    The compound we discovered is a new peptide, Pln149-PEP20, with a molecular framework designed to enhance its antimicrobial activity and with low toxicity. The results can be considered promising insofar as the trials involved pathogenic bacteria associated with MDR infections worldwide.”

    Adriano Andricopulo, co-author of the article

    Although novel antibacterial drugs are urgently needed, the pharmaceutical industry is notoriously uninterested in pursuing them, mainly because research in this field is time-consuming and costly, requiring very long lead times to bring viable active compounds to market.

    The Center for Innovation in Biodiversity and Drug Discovery (CIBFar), a Research, Innovation and Dissemination Center (RIDC) set up and funded by FAPESP, looks for molecules that can be used to combat multidrug-resistant bacteria.

    Camargo and Andricopulo are researchers at CIBFar, as are two other co-authors who study promising bactericidal compounds: Leila Beltramini and José Luiz Lopes.

    For over a decade, the group formed by the collaboration between Beltramini and Lopes has analyzed Plantaricin 149 and its analogs. Plantaricins are substances produced by the bacterium Lactobacillus plantarum to combat other bacteria.

    if (g_displayableSlots.mobileMiddleMrec) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
    }

    Lactobacillus plantarum is commonly found in nature, especially in anaerobic plant matter, and in many fermented vegetable, meat and dairy products.

    In the case of Plantaricin 149, Japanese researchers were the first to report its bactericidal action (in 1994) and since then scientists have been interested in obtaining more efficient synthetic analogs (molecules with small structural differences). In 2007, one of the first projects completed by the CIBFar team showed that the peptide inhibits pathogenic bacteria such as Listeria spp. and Staphylococcus spp. They then began studying synthetic analogs with stronger bactericidal activity than the original (causing more damage to the membrane of the combated microorganisms).

    With the support of a scholarship from FAPESP, Righetto synthesized 20 analogs of Plantaricin 149, finding that Pln149-PEP20 had the best results so far and was also half the size of the original peptide. “The main advances in our research consist of the development of this smaller, more active and less toxic molecule, and the characterization of its action and propensity to develop resistance. It has proven to be highly promising in vitro – active against MDR bacteria and extensively resistant bacteria,” said Camargo, principal investigator for the project.

    LEMiMo, the laboratory where the studies were conducted, has experience in characterizing bacterial isolates involved in outbreaks of hospital infections and holds a collection of bacteria selected for these trials in search of novel active compounds. The bacteria have the resistance profiles currently of greatest concern and were isolated during hospital outbreaks.

    They are known in the scientific community by the term ESKAPE, an acronym for the scientific names of six highly virulent and antibiotic-resistant bacterial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.

    Further research can now be conducted to investigate the molecule’s action mechanism in more depth, to look for formulations, and possibly to develop an application. “In terms of the action mechanism, it’s also possible to use the cell morphology of the bacteria to identify cellular pathways affected by the peptide,” Righetto said. “As for optimization, the molecule can be functionalized by being linked to macrostructures, and the amino acid sequence can be modified.” Research is also needed on its cytotoxicity and on its selectivity (whether it affects healthy cells).

    “We’re living in times of major global public health hazards due to a lack of antimicrobials that can be used to treat infections caused by extremely resistant bacteria. Antimicrobial peptides are targets of great interest for the development of novel candidate drugs. This novel molecule has the potential to be used as an innovative antimicrobial therapy, but further modifications and molecular optimizations still need to be investigated,” Andricopulo said.

    Publication of the article also involved Harvard Medical School’s Infectious Disease Institute in Boston (USA) via researchers Paulo José Martins Bispo and Camille André.

    Source:
    Journal reference:

    Righetto, G. M., et al. (2023). Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria. doi.org/10.3390/antibiotics12020391.

    Study identifies key genetic mechanism of drug resistance in the deadliest malaria parasites

    if (g_displayableSlots.mobileTopLeaderboard) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-top-leaderboard’); });
    }

    An important genetic mechanism of drug resistance in one of the deadliest human malaria parasites has been identified in a new study published in Nature Microbiology.

    A second key gene, pfaat1, responsible for encoding a protein that transports amino acids in the membrane of Plasmodium falciparum, is involved in its resistance to the major anti-malaria drug, chloroquine.

    The findings may have implications for the ongoing battle against malaria, which infects an estimated 247 million people worldwide and kills more than 619,000 each year, most of which are young children.

    Chloroquine is a major antimalaria drug, however in recent years, resistance has emerged in malaria parasites, first spreading through Southeast Asia and then through Africa in the 1970s and 1980s. Although alternative antimalarial drugs have been developed, resistance to chloroquine remains a big challenge.

    Since its discovery in 2000, only one gene has been believed to have been responsible for resistance to chloroquine – the resistance transporter pfcrt which helps the malaria parasite transport the drug out of a key region in their cells, subsequently rendering it ineffective.

    In this study, researchers from the Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine (LSHTM) analysed more than 600 genomes of P. falciparum that were collected in The Gambia over a period of 30 years. The team found that mutant variants of  a second gene, pfaat1, which encodes an amino acid transporter, increased in frequency from undetectable to very high levels between 1984 and 2014. Importantly, their genome-wide population analyses also indicated long term co-selection on this gene alongside the previously-known resistance gene pfcrt.

    In the laboratory, a further team of researchers including from Texas Biomed, University of Notre Dame and Seattle Children’s Research Institute found that replacing these mutations in parasite genomes using CRISPR gene-editing technology impacted drug resistance. A team from Nottingham University also found that these mutations could impact the function of pfaat1 in yeast, resulting in drug resistance.

    if (g_displayableSlots.mobileMiddleMrec) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
    }

    Complementary analysis of malaria genome datasets additionally suggested that parasites from Africa and Asia may carry different mutations in pfaat1 which could help explain differences in the evolution of drug resistance across these continents.

    Alfred Amambua-Ngwa, Professor of Genetic Epidemiology at MRC Unit The Gambia at LSHTM said: “This is a very clear example of natural selection in action – these mutations were preferred and passed on with extremely high frequency in a very short amount of time, suggesting they provide a significant survival advantage.

    “The mutations in pfaat1 very closely mirror the increase of pfcrt mutations. This, and other genetic analyses in the paper demonstrate that the transporter AAT1 has a major role in chloroquine resistance.”

    Grappling with drug resistance, for malaria and other pathogens, requires taking a holistic approach to both drug development and pathogen surveillance. We must be aware that different genes and molecules will be working together to survive treatments. That is why looking at whole genomes and whole populations is so critical.”

    David Conway, Professor of Biology, LSHTM

    if (g_displayableSlots.mobileBottomLeaderboard) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-bottom-leaderboard’); });
    }

    Source:
    Journal reference:

    Amambua-Ngwa, A., et al. (2023). Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1. Nature Microbiology. doi.org/10.1038/s41564-023-01377-z.

    Saving Lives: Study Finds That Paxlovid Reduces Risk of COVID-19 Hospitalization and Death by 90%

    According to a study conducted by Kaiser Permanente, COVID-19 patients who receive prompt treatment with Paxlovid have a significantly reduced risk of hospitalization and death.

    According to a study conducted by Kaiser Permanente and recently published in the journal The Lancet Infectious Diseases, Paxlovid, the combination of nirmatrelvir and ritonavir, has been found to be effective as an early-stage treatment in preventing hospitalization for people with mild to moderate COVID-19, irrespective of their age or prior immunity status.

    “Among Kaiser Permanente members in Southern California who tested positive for coronavirus infection, receiving Paxlovid within 5 days of the start of COVID-19 symptoms was associated with substantial reductions in the risk of hospital admission or death,” said Sara Tartof, Ph.D., the senior author of the study and an epidemiologist with the Kaiser Permanente Southern California Department of Research & Evaluation. “These findings are even more notable because in this population with high levels of vaccination, we still see additional benefits of this treatment.”

    Paxlovid is an oral therapeutic drug aimed at reducing the risk for severe outcomes of coronavirus infection. It is manufactured by Pfizer Inc. It currently has emergency use authorization by the U.S. Food and Drug Administration for adults and children 12 and older who are at high risk for progression to severe COVID-19.

    The study analyses included patients with positive results from coronavirus tests undertaken in outpatient settings between April 8 and October 7, 2022. In the study population, 7,274 people had received Paxlovid, and 126,152 had not received Paxlovid. It was a time dominated by the omicron subvariants BA.2, BA.4, and BA.5. Overall, 86% of the 133,426 participants had received 2 COVID-19 vaccine doses, and 61% had received 3 or more.

    The study found:

    “Our data showed that the sooner people take Paxlovid upon symptom onset, the more effective the medication can be,” Tartof said. “However, there is still some benefit to treatment 6 or more days after symptom onset. People should talk with their doctors about the best approach for them.”

    Reference: “Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system” by Joseph A Lewnard, John M McLaughlin, Debbie Malden, Vennis Hong, Laura Puzniak, Bradley K Ackerson, Bruno J Lewin, Jeniffer S Kim, Sally F Shaw, Harpreet Takhar, Luis Jodar and Sara Y Tartof, 15 March 2023, The Lancet Infectious Diseases.
    DOI: 10.1016/S1473-3099(23)00118-4

    Relaxation of pandemic measures resulted in the surge of Strep A infections to above pre-COVID levels

    if (g_displayableSlots.mobileTopLeaderboard) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-top-leaderboard’); });
    }

    New research from France shows that infections cause by Group A Streptococcus (GAS) fell by 80% as the first COVID lockdown took effect in March 2020 and stayed at low levels until March 2022, from which point they increased by 18% a month to rise well above pre-COVID levels.

    The study is being presented at the European Congress of Clinical Microbiology & Infectious Diseases in Copenhagen, Denmark (15-18 April) and is by Dr Robert Cohen (Association Clinique et Thérapeutique Infantile du Val-de-Marne [ACTIV]), The French Ambulatory Paediatrics Association (AFPA) Paris (France), and Clinical Research Centre, Centre Hospitalier Intercommunal de Créteil – Créteil (France) and colleagues.

    The authors analyzed non-invasive GAS infections in a network of non-emergency pediatricians between January 2018 and December 2022. Clinicians evaluating children aged 15 years old and younger for tonsillopharyngitis, perianal infections, paronychia/blistering dactylitis and scarlet fever (all can be caused by GAS) were invited to perform a rapid antigen detection test (RADT) to confirm the presence of GAS infection.

    The primary outcome was the incidence of non-invasive GAS infections per 10,000 visits over time. Incidence rates were modeled, considering two important timepoints: March 2020 (first national lockdown in France) and March 2022 (mask-wearing in schools no longer mandatory).

    if (g_displayableSlots.mobileMiddleMrec) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
    }

    Over the study period, 125 pediatricians recorded 262,959 episodes of infectious diseases (118,035 children; median age 2.1 years). GAS-related illnesses represented 4.3% (n=11,701) of all infections. In March 2020, the incidence of GAS diseases decreased by around 80%. Between March 2020 and March 2022, the incidence remained low, with no significant trend (Figure). After March 2022, the incidence significantly increased (by 17% per month;), with similar patterns across all GAS-related diseases, reaching levels way above those seen pre-COVID (see figure)

    The authors conclude: “COVID-19 mitigation measures had a major impact on the epidemiology of non-invasive GAS infections, and the relaxation of these measures was followed by a surge of GAS infections to above pre-pandemic levels.”

    Dr Robert Cohen, ACTIV, and the French Ambulatory Paediatrics Association (AFPA) Paris, and Clinical Research Centre, Centre Hospitalier Intercommunal de Créteil – Créteil, France. E) [email protected]

    https://www.news-medical.net/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js
    if (g_displayableSlots.mobileBottomLeaderboard) {
    pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-bottom-leaderboard’); });
    }

    Candida auris infection without epidemiologic links to a prior outbreak

    The Centers for Disease Control and Prevention (CDC) has classified Candida auris (C. auris) as an urgent public threat due to its role in elevating mortality, its ability to persist in hospital environments, and the high possibility of developing pan-drug resistance.

    Notably, a recent study published in the journal Open Forum Infectious Diseases has pointed out that surfaces near patients with C. auris quickly become re-contaminated after cleaning.

    Existing research has not adequately elucidated the environmental reservoirs of C. auris. Further, few studies have reported epidemiologic links associated with C. auris infection. 

    Study: The Emergence and Persistence of Candida auris in Western New York with no Epidemiologic Links: A Failure of Stewardship?. Image Credit: Kateryna Kon / ShutterstockStudy: The Emergence and Persistence of Candida auris in Western New York with no Epidemiologic Links: A Failure of Stewardship? Image Credit: Kateryna Kon / Shutterstock

    Background

    C. auris is a species of fungus that grows as yeast. It is one of the few species of the genus Candida which cause candidiasis in humans. In the past, C. auris infection was primarily found in cancer patients or those subjected to feeding tubes.

    In the United States (US), the emergence of C. auris was traced to New York, and surveillance for this fungal infection was focused mainly on New York City to detect outbreaks. Recently, scientists investigated the association between genomic epidemiology and C. auris infection in Western New York.

    A Case Study

    The study describes the emergence of C. auris in a patient hospitalized at a small community hospital in Genesee County, New York (NY). In January 2022, C. auris was isolated from the urine culture of a 68-year-old male on the 51st day of hospitalization.

    This patient had no known epidemiological connections outside his immediate community. Before his hospitalization, he was not exposed to other patients or family members associated with C. auris infection.

    This patient had no history of organ transplantation, decubitus ulcers, hemodialysis, feeding tubes, or nursing home stays. He had an active lifestyle with a history of mild vascular dementia. He was hospitalized due to pneumonia and was prescribed azithromycin treatment.

    Post hospitalization, he tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and was treated with dexamethasone (6 mg) daily for 10 days and remdesivir (200 mg) once, followed by 100 mg daily for five days.

    Since the patient’s chest radiograph showed left lobar consolidation, he was further treated with empiric ceftriaxone and azithromycin. As the respiratory symptoms deteriorated, he received non-invasive positive pressure ventilation, with subsequent endotracheal intubation for eight days. He was successfully extubated. He developed a fever and received antimicrobial therapy for 73 days. The patient had a urinary catheter and a peripherally inserted central line in his arm for 35 days. 

    Microbiology culture test and serum procalcitonin levels remained negative and within normal levels. On the 22nd day of hospitalization, Candida albicans were isolated from respiratory samples. On the 51st day, the urine culture revealed the presence of azole-resistant C. auris.

    The isolated C. auris (MRSN101498) was forwarded to the Multidrug-resistant organism Repository and Surveillance Network (MRSN), where genomic sequencing was performed. After the patient was discharged, the hospital room was cleaned using hydrogen peroxide and peracetic acid, followed by ultraviolet-C light. Other patients who shared rooms with the patient with C. auris were tested for infection.

    Study Outcomes

    C. auris was not detected in the Western NY community hospital in the past year. Physicians stated that the patient received excessive antibiotic treatment for a prolonged period. Genomic studies revealed that the MRSN101498 genome sequence was closely related to the 2013 Indian strain with minor genomic differences. Interestingly, the K143R mutation in ERG11 was found in MRSN101498, which is associated with triazole resistance in Candida albicans.

    Whole genome single nucleotide polymorphism (SNP) analysis also highlighted that MRSN101498 was strongly genetically related to four other isolates, with marginal differences.

    These isolates were linked to an outbreak in March 2017 in a hospital 47 miles northeast of Rochester, NY. Based on the current findings, it is highly likely that isolates from Western NY share a recent common ancestor.

    Study Importance

    This case study is important for several reasons, including the absence of epidemiologic links to C.auris infection. Since reports from rural sectors are rare, this study addresses a vital surveillance ‘blind spot.’ 

    However, the current study failed to identify the potential reservoirs of MRSN101498 in Western NY. Sporicidal disinfectants were inefficient for both Clostridioides difficile and C. auris. However, terminal cleaning protocols that included UV irradiation and sporicidal cleaning agents were able to eradicate C. auris effectively.

    The current study highlights the role of excessive antibiotic exposure in the emergence of C. auris. It also indicates the challenges in eliminating fungi from hospital settings. The authors recommend proper antibiotic treatment and cleaning procedures for drug-resistant pathogens.

    Journal reference:

    Usefulness of dried blood spot samples for monitoring HCV infection in people who inject drugs

    A study with people who inject drugs evaluated a minimally invasive test based on dried blood spots (DBS) for the monitoring of hepatitis C virus (HCV) infection. The use of DBS samples for HCV RNA detection and genotyping was shown to effectively assess cure after treatment and to differentiate between reinfection and treatment failure. The results support the viability of decentralizing treatment and post-treatment monitoring for people who inject drugs, who frequently face challenges accessing the healthcare system. The study, which has been published in the Journal of Medical Virology, was carried out as part of a project with support from the “Conquering Hepatitis Via Microelimination” (CHIME) programme and a PFIS grant. Investigators from various research institutions collaborated in the project, including the Clinical Virology and New Diagnostic Tools research group, led by Dr Elisa Martró, at Germans Trias i Pujol Research Institute (IGTP) and Dr Sabela Lens from Hospital Clínic’s Viral Hepatitis Group.

    Towards elimination of hepatitis

    In line with the strategy proposed by the World Health Organization for the elimination of viral hepatitis as a public health threat by 2030, and the Plan for Prevention and Control of Hepatitis in Catalonia, which Dr Martró actively participates in, her group has been focused for years on simplifying the diagnosis of hepatitis C by developing and validating an assay which can detect the virus RNA using DBS samples. These minimally invasive samples can be collected at harm reduction centres or drug dependence care and follow-up centers (known as CAS in Catalan), improving access to hepatitis C diagnosis for vulnerable populations, such as people who inject drugs. While this new test has demonstrated good clinical performance as a diagnostic tool for detecting HCV RNA before treatment in previous studies by the Clinical Virology and New Diagnostic Tools research group, the use of DBS samples had not been evaluated as a test for cure or for detecting reinfection after treatment.

    A multidisciplinary research group has been able to pursue a project with a new model of care for hepatitis C, based on point-of-care diagnosis, treatment, and reinfection follow-up at the REDAN La Mina harm reduction centre. Since 2019, approximately 750 individuals who inject drugs have been tested though this initiative, which was designed by Dr Sabela Lens from Hospital Clínic’s Viral Hepatitis Unit, in collaboration with the Clinical Virology and New Diagnostic Tools Research Group at Germans Trias i Pujol Research Institute (IGTP), led by Dr Martró from the Microbiology Service (LCMN) of the Germans Trias i Pujol Hospital (HUGTiP), as well as CEEISCAT and the Public Health Agency of Catalonia. The project had the support of the “Conquering Hepatitis Via Microelimination” (CHIME) programme from Gilead Sciences awarded to Dr Lens, as well as a PFIS grant of the Instituto de Salud Carlos III and the Fondo Social Europeo awarded to Anna Not, who is a member of Dr Martró’s group, and aligns with the World Health Organization’s global health strategy, which aims to eliminate hepatitis C as a public health problem by 2030.

    A model of decentralized care

    In this project, Dr Martró’s group aimed to evaluate the clinical performance of a previously developed HCV-RNA assay based on DBS, for the assessment of cure and the detection of recurrent viremia after on-site treatment at the harm reduction center, compared to the commercially available HCV-RNA point-of-care test. Furthermore, they sought to assess the possibility of distinguishing between reinfection and treatment failure through HCV genotyping from baseline and follow-up DBS samples. Typically, these assessments (cure and reinfection) are performed using venipuncture blood samples collected at healthcare centres, which can be difficult for people who inject drugs and have often limited access to the healthcare system. The recently published results demonstrate how the collection of DBS samples before and after treatment can simplify these assessments in decentralized test-and-treat programmes.

    “The success of the CHIME project lies in the decentralized diagnosis and treatment provided at REDAN La Mina. A nurse trained in hepatology assessments was included in the study to enrol and visit participants. The hepatologists at Hospital Clínic also reviewed each case and prescribed decentralized treatment. Additionally, Dr Martró’s group carried out HCV detection and sequencing from DBS samples collected before and after treatment. This pilot program involves HCV diagnosis on-site in less than an hour, treatment at the same center, and follow-up to assess reinfection”, states Dr Lens.

    Detection made easier

    Reinfection is common in people who inject drugs and must be treated to prevent further transmission of the virus. During early reinfection, low levels of the virus may be present, making its detection in DBS samples challenging, as they only contain a small amount of blood. Of the 193 DBS samples tested after treatment, the DBS-based assay showed 100% specificity and sensitivity ranging from 84% to 96% based on different relevant viral load cut-offs, and similar rates as a test of cure (three months after treatment). It must be born in mind that among the patients with recurrent viremia after treatment, one tenth had low viral loads. Moreover, HCV genotyping allowed researchers to classify 73% of viremic cases as either reinfection or treatment failure.

    Collection of DBS samples was done before antiviral treatment and after treatment if recurrent viremia was detected by the commercially available point-of-care assay. Anna Not, the first author of the article (which will be part of her PhD), explains that it “the use of DBS allowed us to sequence the virus before and after treatment and compare the sequences to determine if the virus was the same (indicating a treatment failure) or if it was different (indicating reinfection). This information enabled the hepatologist to decide on the most appropriate antiviral combination for the second treatment”.

    The research shows the potential of using DBS samples for determining cure and differentiating between reinfection and relapse after antiviral treatment for hepatitis C in people who inject drugs. The use of DBS samples makes it possible to decentralize treatment and follow-up, improving access to care for these people. Even so, Dr Martró points out that “a small number of patients had low viral loads, which can hinder the detection of viremia and genotyping in DBS. As a result, repeat testing (e.g. every six months) is advised for individuals who are at risk of HCV reinfection”.

    Source:
    Journal reference:

    Not, A., et al. (2023) Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test-and-treat program. Journal of Medical Virology. doi.org/10.1002/jmv.28544.

    A variety of studies have shown that when the air is drier, viral particles can linger there longer. …

    A variety of studies have shown that when the air is drier, viral particles can linger there longer. These findings have now been confirmed in an analysis of particles of a virus that is very similar to the one that causes COVID-19, SARS-CoV-2. Although previous work has shown that relative humidity levels affect the length of time of a virus stays infectious in the air, this is the first to factor in the effect of saliva, which helps shield viral particles. The data can help explain why people tend to get more sick during winter, when humidity levels drop significantly indoors. It also stresses the importance of good ventilation systems and other mitigation efforts for preventing the spread of illness. The work has been reported in PNAS Nexus.

    Dr. Mark Hernandez, S. J. Archuleta Professor of Civil and Environmental Engineering, and CU PhD graduate Marina Nieto-Caballero, now a postdoctoral researcher at Colorado State University, standing inside a bioaerosol chamber in the Environmental Engineering disinfection laboratory at the Sustainability, Energy and Environment Complex (SEEC). Credit  Patrick Campbell/University of Colorado

    This study used a mammalian coronavirus that is very similar to SARS-CoV-2. Particles containing this virus remained infectious for twice as long when air was drier. These particles are normally expelled with saliva, which acts like a protective shield, particularly when humidity is low.

    Although civil engineers typically design and maintain buildings so their indoor relative humidity will stay between 40 and 60 percent, the reality is a bit different, and varies widely depending on the climate of the region. The researchers suspected that these humidity levels were influencing the spread of SARS-CoV-2.

    To test that theory, the investigators engineered airborne particles containing virus, with and without saliva. These were then released into large, sealed chambers with relative humidity levels of 25, 40, and 60 percent.

    The saliva protected the virus at every humidity level, and at 40 and 60 percent relative humidity, half of the airborne viral particles were still infectious one hour after release. Half of the airborne particles were still infectious two hours after release at 25 percent humidity; as the relative humidity dropped, the virus was still pathogenic for much longer.

    “It shows this virus can hang around for quite a while, hours even. It’s longer than a class, longer than the time you’re in a restaurant, longer than the time you take to hang out in the cafe. An occupant may come in, spread coronavirus in the air, and leave. Depending on architectural factors, then someone else could walk into that space with potent doses still hanging around,” said senior study author Mark Hernandez, a Professor of Civil and Environmental Engineering at the University of Colorado at Boulder.

    The virus is probably also contaminating air for longer than it takes typical ventilation systems to eliminate it. Thus, additional mitigation strategies like filtration could reduce transmission, suggested the study authors.

    “I hope this paper has an engineering impact in our buildings, for example, in schools and hospitals, so that we can minimize the infectivity of these viruses in the air,” said lead study author Marina Nieto-Caballero, PhD.

    Increasing indoor humidity levels could help reduce risk for people who live in naturally arid environments, but that can be inefficient and expensive, said Hernandez. We can use strategies that we already know about instead, like opening windows, using inexpensive air filters, and increasing ventilation rates to introduce more fresh air, Hernandez added.

    Sources: University of Colorado at Boulder, PNAS Nexus


    Carmen Leitch

    What is spillover? Bird flu outbreak underscores need for early detection to prevent the next big pandemic

    The current epidemic of avian influenza has killed over 58 million birds in the U.S. as of February 2023. Following on the heels of the COVID-19 pandemic, large outbreaks of viruses like bird flu raise the specter of another disease jumping from animals into humans. This process is called spillover.

    I’m a veterinarian and a researcher who studies how diseases spread between animals and people. I was on the Colorado State University veterinary diagnostic team that helped detect some of the earliest cases of H5N1 avian influenza in U.S. birds in 2022. As this year’s outbreak of bird flu grows, people are understandably worried about spillover.

    Given that the next potential pandemic will likely originate from animals, it’s important to understand how and why spillover occurs – and what can be done to stop it.

    Spillover involves any type of disease-causing pathogen, be it a virus, parasite or bacteria, jumping into humans. The pathogen can be something never before seen in people, such as a new Ebola virus carried by bats, or it could be something well known and recurring, like Salmonella from farm animals.

    The term spillover evokes images of a container of liquid overflowing, and this image is a great metaphor for how the process works.

    Imagine water being poured into a cup. If the water level keeps increasing, the water will flow over the rim, and anything nearby could get splashed. In viral spillover, the cup is an animal population, the water is a zoonotic disease capable of spreading from an animal to a person, and humans are the ones standing in the splash zone.

    The probability that a spillover will occur depends on many biological and social factors, including the rate and severity of animal infections, environmental pressure on the disease to evolve and the amount of close contact between infected animals and people.

    While not all animal viruses or other pathogens are capable of spilling over into people, up to three-quarters of all new human infectious diseases have originated from animals. There’s a good chance the next big pandemic risk will arise from spillover, and the more that’s known about how spillovers occur, the better chance there is at preventing it.

    Most spillover research today is focused on learning about and preventing viruses – including coronaviruses, like the one that causes COVID-19 and certain viral lineages of avian influenza – from jumping into humans. These viruses mutate very quickly, and random changes in their genetic code could eventually allow them to infect humans.

    Spillover events can be hard to detect, flying under the radar without leading to bigger outbreaks. Sometimes a virus that transfers from animals to humans poses no risk to people if the virus is not well adapted to human biology. But the more often this jump occurs, the higher the chances a dangerous pathogen will adapt and take off.

    Epidemiologists are projecting that the risk of spillover from wildlife into humans will increase in coming years, in large part because of the destruction of nature and encroachment of humans into previously wild places.

    Because of habitat loss, climate change and changes in land use, humanity is collectively jostling the table that is holding up that cup of water. With less stability, spillover becomes more likely as animals are stressed, crowded and on the move.

    As development expands into new habitats, wild animals come into closer contact with people – and, importantly, the food supply. The mixing of wildlife and farm animals greatly amplifies the risk that a disease will jump species and spread like wildfire among farm animals. Poultry across the U.S. are experiencing this now, thanks to a new form of avian flu that experts think spread to chicken farms mostly through migrating ducks.

    The new avian influenza virus is a distant descendant of the original H5N1 strain that has caused human epidemics of bird flu in the past. Health officials are detecting cases of this new flu virus jumping from birds to other mammals – like foxes, skunks and bears.

    On Feb. 23, 2023, news outlets began reporting a few confirmed infections of people in Cambodia, including one infection leading to the death of an 11-year-old girl. While this new strain of bird flu can infect people in rare situations, it isn’t very good at doing so, because it is not able to bind to cells in human respiratory tracts very effectively. For now, the Centers for Disease Control and Prevention thinks there is low risk to the general public.

    Active monitoring of wild animals, farm animals and humans will allow health officials to detect the first sign of spillover and help prevent a small viral splash from turning into a large outbreak. Moving forward, researchers and policymakers can take steps to prevent spillover events by preserving nature, keeping wildlife wild and separate from livestock and improving early detection of novel infections in people and animals.


    Treana Mayer

    The Conversation

    First clinical trial of GABA/GAD focused exclusively on children with recent onset Type 1 diabetes

    For the first time, humans with newly diagnosed Type 1 diabetes, or T1D, have received two treatments called GABA and GAD that have shown promise in animal studies and in isolated human pancreas islets. This investigator-initiated clinical trial, published in Nature Communications, focused exclusively on children with recent onset T1D.

    Diabetes is a disease affecting two pancreatic hormones -; insulin and glucagon. In healthy people, insulin helps cells take up glucose from the blood when glucose levels are high. In contrast, glucagon helps the liver release glucose into the bloodstream when glucose levels are low. Thus, levels of blood glucose remain steady.

    In T1D, autoantibodies destroy the pancreatic beta cells, insulin release is diminished, and glucagon release is excessive relative to the insulin deficiency. This can cause a vicious cycle of escalating blood glucose levels. Strategies to ameliorate or cure T1D, therefore, target the preservation of insulin-secreting beta cells and/or attenuation of the relative excess of alpha cell glucagon. Most importantly, concerning the inhibition of alpha cell glucagon in this trial by GABA/GAD, recent studies in animals made diabetic have shown that inhibition of glucagon leads to expansion of insulin-secreting beta cells and improvements in hyperglycemia.

    Researchers in the study, led by University of Alabama at Birmingham physicians, were able to enroll children within the first five weeks of diagnosis, before the near total eradication of beta cells. Forty percent of the study participants were younger than 10 years old. The study -; which was constrained to lower-dose GABA therapy by the United States Food and Drug Administration because it was the first human trial with GABA -; did not achieve its primary outcome, the preservation of insulin production by beta cells. However, it did meet the clinically relevant secondary outcome of reduced serum glucagon. Significantly, the trial confirmed the safety and tolerability of oral GABA. Additionally, in collaboration with the immunology team of Hubert Tse, Ph.D., at the UAB Comprehensive Diabetes Center, a separate manuscript under review will describe a salutary effect of GABA alone and in combination with GAD on cytokine responses in peripheral blood mononuclear cells from trial participants.

    GABA is gamma aminobutyric acid, a major inhibitory neurotransmitter. In the endocrine pancreas, GABA participates in paracrine regulation -; meaning a hormone that acts on nearby cells -; on the beta cells that produce insulin and the alpha cells that produce glucagon. In various mouse model studies, GABA was able to delay diabetes onset, and restore normal blood glucose levels after diabetes had already commenced. GABA treatment also led to significant decreases in the inflammatory cytokine expression that participates in the pathogenesis of T1D.

    GAD is glutamic acid decarboxylase, the enzyme that acts on glutamate to form GABA. Animal and pancreatic islet cell studies show that immunization with GAD alone may help preserve beta cells. Both GABA and GAD are highly concentrated in the pancreatic islet, which is the autoimmune target of T1D.

    The study, which was conducted between March 2015 and June 2019, screened 350 patients and enrolled 97, whose ages averaged 11 years. Forty-one took oral GABA twice a day; 25 took the oral GABA in combination with two injections of GAD, one at the baseline visit and one at the one-month visit. The remaining 31 children received a placebo treatment. Analysis after one year of treatment included 39 in the GABA group, 22 in the GABA/GAD group and 30 in the placebo group.

    Given that GABA reduces immune inflammation at higher doses in several diabetic rodent models, it is plausible that increased GABA doses, or longer-acting preparations, could offer sufficiently prolonged, above-threshold GABA concentrations to preserve islet cells, particularly during stage 1 diabetes.”

    Gail Mick, M.D., UAB Professor in the Department of Pediatrics’ Division of Pediatric Endocrinology and Diabetes

    Mick and Kenneth McCormick, M.D., who recently retired from UAB Pediatrics, co-led the trial.

    Alexandra Martin and Mick, UAB Department of Pediatrics, are co-first authors of the study, “A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes.”

    Other authors are Heather M. Choat, Alison A. Lunsford and Kenneth L. McCormick, UAB Department of Pediatrics; Hubert M. Tse, UAB Department of Microbiology; and Gerald G. McGwin Jr., Department of Epidemiology, UAB School of Public Health.

    Source:
    Journal reference:

    Martin, A., et al. (2022) A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes. Nature Communications. doi.org/10.1038/s41467-022-35544-3.