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Tag: Infectious Diseases

  • Undernourished household contacts three times more likely to develop TB

    Undernourished household contacts three times more likely to develop TB

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    Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), is distinct from most germs in its capacity to silently infect individuals for months and even years before waking up and causing active disease that can lead to severe illness and death. The immune system plays an important role in controlling the germ and keeping it dormant.

    Decades of epidemiological data have linked undernutrition to TB. While undernourished individuals have blunted immune systems, a phenomenon which has been dubbed nutritionally acquired immune deficiency (N-AIDS), it is not clear why undernourished individuals are at increased risk of TB disease.

    In a new study that followed household contacts (family members/people who share the same dwelling) of persons with TB, researchers have found that undernourished household contacts were three times more likely to progress to TB disease. The study did not find that undernourished contacts were at increased risk of testing positive for TB infection as compared to well-nourished individuals.

    Are they more likely to become infected with the TB germ? Or are their immune systems unable to contain the germ resulting in severe disease? This fundamental question is important to answer as it can guide how we can best protect undernourished individuals who form a key and vulnerable population in the fight against TB.”


    Pranay Sinha, MD, corresponding author, assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine

    The researchers, which included investigators from both U.S. and Indian institutions (which are part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India consortium), identified nearly 900 household contacts of persons who were newly diagnosed with TB, screening them to make sure they did not have TB disease at enrollment. They then followed these contacts to see if they developed TB disease for up to four years. Those who had a negative TB infection test at enrollment were retested to see if it had turned positive. The researchers then compared the rate of TB disease and TB infection between undernourished household contacts and well-nourished household contacts.

    According to the researchers, these findings have clinical implications. “We now have greater insight into the mechanism by which undernutrition leads to greater TB risk. It is not by increasing infection, instead, it is by failing to contain the infection when it happens. Fortunately, undernutrition is a modifiable risk factor. Our findings should prompt TB programs to promptly provide adequate rations for the entire household to prevent TB disease among household contacts in addition to TB preventive therapy,” adds Sinha.

    These findings appear online in the journal Clinical Infectious Diseases.

    Source:

    Boston University School of Medicine

    Journal reference:

    Sinha, P., et al. (2024) Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection— a Multicenter Prospective Cohort Analysis. Clinical Infectious Diseases. doi.org/10.1093/cid/ciae149.

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  • Hospital sinks fuel antibiotic-resistant bacteria spread

    Hospital sinks fuel antibiotic-resistant bacteria spread

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    A new study published today in the American Journal of Infection Control (AJIC) reports the infection prevention steps taken to control a months-long multispecies outbreak of carbapenemase-producing Enterobacterales that occurred in a pediatric ward at the Toho University Omori Medical Center in Tokyo in 2017. This study highlights the particular vulnerability for contamination through sinks and other water sources; indeed, even replacing all sinks in the ward did not stop this outbreak.

    Carbapenemase-producing Enterobacterales (CPE) are a major public health threat because of their resistance to widely used antibiotics. The biological mechanism that confers multidrug resistance can be passed from one bacterial species to another, contributing to the growing epidemic of antimicrobial resistance. An outbreak of one CPE species in a hospital has the potential to turn into an outbreak involving many species, making it that much more difficult to stop. Many studies have shown that there is a high risk of CPE contamination in and around hospital sinks.

    This new report from an academic medical center in Tokyo details the detection of CPE in a single patient in June 2016, which appears to have triggered an outbreak starting in March 2017 and ending in October 2017. The outbreak involved a total of 19 pediatric patients. The infection prevention team sampled microbes from patients and the environment of the pediatric ward to better understand how the outbreak was spreading. This sampling identified nine sinks contaminated with CPE, including six in hospital rooms and three more in a nurse center, a waste room, and an ice machine. The CPE-positive sinks were all found in rooms where CPE-positive patients had been treated. In rooms with CPE-negative patients, no sink contamination was detected.

    As part of the outbreak control process, genome analysis was performed to identify the specific resistance mechanisms found in the bacterial strains, which included Klebsiella variicola, Klebsiella quasipneumoniae, and Escherichia coli, among others. Identical DNA sequences from all samples but one support the idea that the resistance mechanism could have been passed from one bacterial species to another within the hospital.

    To help rein in the outbreak, all sinks in the pediatric ward were replaced with new ones in June 2017, and the new sinks were thoroughly disinfected with hydrogen peroxide. However, CPE contamination continued even after that step. The discovery of the same bacterial species in sinks in adjoining rooms indicates that pathogen transmission may be possible from one sink to another via the drains and connected plumbing.

    Other measures implemented by the infection prevention team -; composed of doctors, nurses, pharmacists, and microbiologists -; included recommending hand disinfection after using sinks, introducing disposable tools for cleaning sinks, prohibiting mouth-washing with sink water, enacting disinfection and drying procedures to any items exposed to sink water, and more. Finally, after October 2017, no further CPE contamination was identified in patient samples or environmental surveillance.

    After months of intense infection control protocols, we were at last able to declare an end to this outbreak. Our experience highlights the importance of focusing on sinks and other water-related areas in hospital wards, as these are critical for CPE transmission and therefore major fronts in the fight against antibiotic resistance.”

    Sadako Yoshizawa, MD, PhD, Associate Professor in the Department of Microbiology and Infectious Diseases at Toho University School of Medicine, Deputy Director of Clinical Laboratory at Toho University Omori Medical Center, and corresponding author of the study

    Additional details from the study include:

    • Toho University Omori Medical Center is a 916-bed academic medical center with 55 pediatric inpatient beds.

    • The first patient to be detected with CPE in June 2016 was a one-year-old boy hospitalized with cardiac disease.

    • The resistance mechanism detected in this outbreak was a plasmid enabling the production of carbapenemase, which can make bacteria resistant to the carbapenem class of antibiotics. In this outbreak, all CPE strains except one harbored blaIMP-1, with identical blaIMP-1-carrying IncM1 plasmids.

    The tremendous effort that went into controlling this outbreak is representative of the comprehensive and holistic approach to infection prevention that is required in these situations. Even a measure as definitive as replacing contaminated sinks may not be enough to stop the spread of antibiotic-resistant organisms. This outbreak ended because the infection prevention team implemented a bundle of core processes related to hand hygiene, and the use and disinfection of hospital sinks.”


    Tania Bubb, PhD, RN, CIC, FAPIC, 2024 APIC president

    Source:

    Association for Professionals in Infection Control

    Journal reference:

    Tsukada, M., et al. (2024) The outbreak of multispecies carbapenemase-producing Enterobacterales associated with pediatric ward sinks: IncM1 plasmids act as vehicles for cross-species transmission. American Journal of Infection Control. doi.org/10.1016/j.ajic.2024.02.013.

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  • Rising antibiotic resistance prompts shift to ecological research strategies in infection control

    Rising antibiotic resistance prompts shift to ecological research strategies in infection control

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    In a recent article published in The Lancet Microbe, researchers discussed the need to enhance research on the interactions between bacterial pathogens and commensals within human microbiomes and host biology to develop innovative infection prevention and treatment strategies.

    Study: Integrating research on bacterial pathogens and commensals to fight infections—an ecological perspective. Image Credit: TopMicrobialStock/Shutterstock.comStudy: Integrating research on bacterial pathogens and commensals to fight infections—an ecological perspective. Image Credit: TopMicrobialStock/Shutterstock.com

    Background

    The growing appreciation of the human microbiome’s role in health drives innovative disease prevention and treatment approaches.

    This includes using microbiome signatures as biomarkers for diagnosing various diseases and exploring interventions like fecal microbiota transplantation.

    Historically, research focused more on pathogens, but now, understanding the dynamic roles of pathogens and commensals is essential. Interdisciplinary collaboration offers new insights into the ecological factors driving bacterial behavior and the development of preventive and therapeutic strategies for infections.

    This convergence of microbiome science and innovative approaches holds great potential for promoting human health.

    Future research on commensal bacteria inspired by that on pathogens

    Research on commensal bacteria is gaining momentum, inspired by the extensive study of major bacterial pathogens like Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumoniae.

    While pathogens have been extensively studied, commensals, particularly those from genera like Bacteroides, Clostridium, and Cutibacterium, have received less attention despite their potential clinical significance.

    Evidence suggests that certain commensals play crucial roles in human health, producing compounds that inhibit pathogens and those that directly benefit the host. Understanding the host-specificity and biology of these beneficial commensals could offer insights into combating bacterial infections.

    Additionally, exploring the mechanisms behind commensal-host interactions, such as adhesion to epithelial surfaces and modulation of mucosal immunity, could provide further avenues for research.

    Expanding our understanding of fitness mechanisms of facultative human pathogens

    Research on facultative human pathogens, which typically exist as commensals but can cause disease under certain conditions, is gaining importance, considering the global rise in antimicrobial resistance.

    While much attention has been given to understanding the virulence mechanisms of major pathogens like S. aureus and S. pneumoniae, the factors influencing the fitness of these organisms during their commensal phase have been largely overlooked.

    This oversight is particularly concerning given the increasing prevalence of antibiotic-resistant pathogens, including those grouped as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp).

    Understanding why certain antibiotic-resistant clones spread more effectively than others is crucial for developing effective control strategies.

    Applying ecological concepts to studying pathogenic bacteria could shed light on their success in competing with other microbiome members. Factors such as nutrient utilization, resistance to antimicrobial molecules, and adhesion to host epithelial surfaces play important roles in determining a bacterial species’ long-term success within a host and its ability to spread to new hosts.

    Investigating the mechanisms underlying vertical and lateral transmission of bacteria is also crucial, as it can provide insights into the dynamics of microbiome colonization and infection spread.

    The severity and type of infection caused by pathogens can influence their spread among hosts. For example, pathogens like S. flexneri, causing diarrheal diseases, may spread through contaminated sewage, while those like S. aureus, causing skin infections, may spread through direct contact between individuals.

    Accidental pathogens, which typically lack aggressive toxins but possess immune-evasion mechanisms, may persist in human microbiomes more readily than professional pathogens.

    However, professional pathogens can also cause opportunistic infections, particularly in immunocompromised individuals.

    Integrative understanding of fitness of bacterial commensals and pathogens can help with infection prevention

    Understanding commensal and pathogenic bacteria within their natural habitats can provide valuable insights for controlling infections and addressing microbiome-related disorders.

    Commensal bacteria exhibit complex effects on infectious diseases, employing various defense strategies such as antimicrobial production and metabolic interference to inhibit pathogen colonization.

    Microbiome restoration through fecal microbiota transplantation has shown promise in treating infections, but standardized approaches are needed. Utilizing defined commensal communities for microbiome editing could offer more consistent results and personalized treatment options.

    However, antibiotic treatment, primarily with broad-spectrum antibiotics, can disrupt the microbiome and fuel antibiotic resistance.

    Commensals play a crucial role in resistance gene transfer to pathogens, highlighting the need to monitor key commensal species alongside major pathogens.

    Ecological approaches to infection research can help identify vulnerabilities in pathogens, leading to the development of targeted anti-fitness drugs and anti-virulence compounds. Understanding the interplay between pathogens and mucosal immunity is essential for developing mucosal vaccines against potentially pathogenic microbiome members.

    Conclusion

    In conclusion, understanding the interaction between commensal and pathogenic bacteria within their ecological contexts offers promising avenues for infection prevention and treatment.

    By leveraging the protective mechanisms of commensals and targeting pathogen virulence, tailored interventions can enhance host defenses and suppress pathogen proliferation.

    Moreover, the development of mucosal vaccines and microbiome-based therapies offers new strategies for infection control. Integrating ecological principles into infection research provides a holistic framework for combating infectious diseases and addressing antimicrobial resistance, ultimately optimizing human health.

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  • Annual COVID-19 vaccine proves to be a wise investment for personal health and pocketbook

    Annual COVID-19 vaccine proves to be a wise investment for personal health and pocketbook

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    In a recent study published in The Journal of Infectious Diseases, a team of researchers from the United States (U.S.) attempted to understand whether individuals experienced any economic benefits in getting an annual coronavirus disease 2019 (COVID-19) vaccine, given that the morbidity and mortality rates associated with the disease have decreased and the government no longer covers the vaccine costs.

    Study: What is the economic benefit of annual COVID-19 vaccination from the adult individual perspective? Image Credit: eamesBot / ShutterstockStudy: What is the economic benefit of annual COVID-19 vaccination from the adult individual perspective? Image Credit: eamesBot / Shutterstock

    Background

    The rapid development of vaccines to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has helped significantly reduce the disease’s severity and limit the transmission of the virus. Although subvariants of SARS-CoV-2 continue to emerge and circulate, the virus’s virulence and transmissibility seem to have reduced due to the protection afforded by large-scale vaccination efforts worldwide.

    With the drop in hospitalization and mortality rates, COVID-19 is no longer considered a significant public health risk, leading to a substantial decrease in vaccination rates across the U.S. Furthermore, employment organizations and businesses are no longer mandating booster  COVID-19 vaccination shots. With the government no longer funding the cost of the vaccine, individuals have to pay for the COVID-19 booster shots either out-of-pocket or through their insurance. However, the gradual decrease in vaccination coverage and waning of infection-induced immunity could influence the control of viral transmission and disease severity.

    About the study

    In the present study, the researchers examined the benefits of getting annual COVID-19 vaccines, similar to the influenza vaccine, from an individual perspective instead of from the perspective of a third-party payer or society, which has already been examined in previous studies. The researchers believe that while the findings might not contribute to recommendations and decisions made by governments or insurance companies, they will help individuals assess the merits of an annual COVID-19 vaccination from their perspective.

    The study developed and used a Markov computational simulation model to assess the values and trade-offs of getting the annual vaccine. This model used eight mutually exclusive states of SARS-CoV-2 infections and the economic and clinical outcomes for each state.

    The state at which an individual begins is the state of no infection with pre-existing protection from previous vaccinations or infections. Based on factors such as risk of infection, probability of clinical outcomes based on age, and pre-existing protection levels, the model calculates the probability of an individual moving to a COVID-19 state. The model also calculates the probabilities of returning to the non-infected state or developing long COVID based on various levels of symptoms ranging from asymptomatic to severe.

    These probabilities are calculated twice for each individual, once with and once without the annual COVID-19 vaccination. Minor to severe adverse effects, as well as changing vaccine efficacy, are also factors that are incorporated into the model. The economic measures are calculated based on factors such as loss of productivity due to vaccination absenteeism, mortality, out-of-pocket costs, presenteeism, healthcare visits, and medications. The cost-benefits were calculated for each scenario. Sensitivity analyses were also conducted for varying disease severity based on different SARS-CoV-2 variants.

    Results

    The results suggested that an individual stood to benefit clinically and economically by getting vaccinated annually against COVID-19. The model showed that adults between the ages of 18 and 49 saved an average of $30 to $603 if they did not have health insurance, while insured individuals of the same age group saved $4 to $437.

    These estimates were on the assumption that the efficacy of the vaccine against SARS-CoV-2 started at greater than or equal to 50%, the individuals interacted with about nine people a day, the infection probability was more significant than or equal to 0.2%, the infection prevalence was 10%, and the conditions were for the Omicron variant of SARS-CoV-2 during the winter of 2023-2024.

    For individuals between the ages of 50 and 64, the average economic benefits were even higher, with savings of $119 to $1706 and $111 to $1278 for individuals with and without insurance, respectively. Furthermore, in cases where the previous vaccination was nine months ago, and 13.4% of the pre-existing protection remained, the model showed that the risk threshold was greater than or equal to 0.4%.

    Conclusions

    Overall, the study found that the annual COVID-19 vaccine was economically and clinically beneficial to individuals with or without health insurance. The economic value of getting the COVID-19 vaccine was higher for individuals between 50 and 64 years of age.

    Journal reference:

    • Bartsch, S. M., O’Shea, K. J., Weatherwax, C., Strych, U., Velmurugan, K., John, D. C., Bottazzi, M. E., Hussein, M., Martinez, M. F., Chin, K. L., Ciciriello, A., Heneghan, J., Dibbs, A., Scannell, S. A., Hotez, P. J., & Lee, B. Y. (2024). What is the economic benefit of annual COVID-19 vaccination from the adult individual perspective? The Journal of Infectious Diseases. DOI: 10.1093/infdis/jiae179, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae179/7641782 

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  • ChatGPT could be an effective tool to help reduce vaccine hesitancy

    ChatGPT could be an effective tool to help reduce vaccine hesitancy

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    New research being presented at this year’s ESCMID Global Congress (formerly ECCMID) in Barcelona, Spain (27-30 April) suggests that the free-to-use, widely accessible ChatGPT could be an effective tool to help reduce vaccine hesitancy among the general public, as well as providing helpful advice on sexually transmitted infections (STIs) in conjunction with sexual health clinics, by improving knowledge and access to care.

    Our findings showed that ChatGPT displayed a remarkable ability to accurately respond to a wide breadth of commonly asked questions, encompassing topics such as misconceptions around mRNA vaccination and the importance of testing for STIs. In the majority of instances, ChatGPT performed at the level of advice provided by professional organizations and guidelines.”

    Dr Matthew Koh,lead author from the National University Health System (NUHS) in Singapore

    Since its unveiling in November 2022, millions of people have used AI (artificial intelligence) chatbots like ChatGPT for everything from making music to answering trivia to helping with homework. But ChatGPT has been mired in issues around its accuracy.

    Vaccines have stopped epidemics and almost eradicated deadly diseases in the past such as polio, but vaccine hesitancy, directly linked to misinformation-;false, inaccurate information promoted as factual-;is on the rise, resulting in lower vaccine uptake. Since the public debut of ChatGPT, individuals with mistrust of health professionals may be using the technology to address their concerns.

    Similarly, for individuals trying to access information on sexual health, or those worried about the stigma and embarrassment of attending a clinic, or with limited access to healthcare, could find using ChatGPT is a good way to get answers about STIs.

    To find out more, researchers from the NUHS in Singapore tested ChatGPT to see whether it could successfully provide answers to common questions about vaccination and STIs.

    A team of physicians who run infectious disease clinics asked ChatGPT to answer 15 commonly asked questions on vaccine hesitancy, including questions on doubts about the efficacy of vaccines, concerns about adverse effects, and cultural concerns relating to vaccines (see table in notes to editors).

    They also asked ChatGPT 17 common questions on STIs based on general risk factors, access to care and diagnosis, and management and post-exposure prophylaxis (see table in notes to editors).

    The AI-generated responses on vaccine hesitancy were then assessed by two independent infectious disease experts against recommendations from the US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), and the chatbot answers on STIs were assessed against the 2021 US CDC STI Treatment Guidelines. All responses were evaluated for their completeness, quality, and accuracy.

    Factual responses to vaccine hesitancy concerns

    The researchers found that overall ChatGPT’s output provided factual responses and reassurance to vaccine hesitancy concerns.

    For example, ChatGPT accurately highlighted the indication for measles vaccination in low incidence settings, and discussed the potential benefits of male human papillomavirus (HPV) vaccination. However, the AI chatbot failed to acknowledge the suggested ACIP age cut-offs for HPV vaccination, or account for a specific individual’s situation such as how sexually active they are.

    In addition, ChatGPT provided reassurances for people with an egg allergy and influenza vaccination, and addressed misconceptions around mRNA vaccination and permanent alterations in DNA with high accuracy. However, it did not offer the non-mRNA vaccine options for COVID-19, but did encourage further discussions with healthcare professionals.

    ChatGPT also appropriately acknowledged the complexity of religious issues around vaccination and directed individuals to have further discussions with religious leaders. Importantly, however, the researchers found that without specific details of the religious concern and the specific vaccine, ChatGPT’s advice was generic and it did not provide a more detailed risk-benefit discussion.

    “Overall, ChatGPT’s responses to vaccine hesitancy were accurate and may help individuals who have vaccine-related misconceptions”, says Dr Koh, who is also an infectious diseases physician at the National University Hospital in Singapore. “Our results demonstrate the potential power of AI models to assist in public health campaigns and aid health professionals in reducing vaccine hesitancy.”

    STI responses generally accurate and concise

    The researchers also found that overall, ChatGPT’s responses on STIs were mostly accurate and concise.

    For example, when asked about how to prevent STIs, the chatbot recommended safe sex practices HPV vaccinations as well as abstinence, but it failed to provide guidance on other key elements such as HIV pre-exposure prophylaxis.

    In addition, the AI chatbot was able to provide general reassurance about STI symptoms, such as noting that other possibilities exist, and recommended going for testing. It also consistently communicated the importance of partner testing and follow-up testing.

    However, when asked about chlamydia treatment, ChatGPT suggested either azithromycin or doxycycline, although the CDC favors doxycycline as the first-line treatment. It also failed to highlight the importance of testing for other STIs.

    “ChatGPT provided good general advice about STIs, but it lacked specificity and could not tailor its advice to individual’s risk of acquiring STIs”, says Dr Koh. “The goal of this project is to empower the general public. The hope is that individuals can educate themselves with ChatGPT by making accurate advice more accessible and increase vaccine uptake and protection from STIs.”

    He continues “We believe that ChatGPT should be used in conjunction with, or in addition to, a physician consultation-;the human response is still needed to contextualize the advice that is given to a specific individual’s situation and for it to make the most sense and be the most helpful for the patient.”

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  • A balanced take on microbes and disease outcomes

    A balanced take on microbes and disease outcomes

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    In a recent review published in the journal PNAS, researchers examined the germ theory from a non-centric perspective on infection outcome, considering the variables that influence illness severity while drawing on a known understanding of microbial pathogenesis, evolutionary biology, and pathogen-host interactions.

    The germ theory revisited: A noncentric view on infection outcome. Image Credit: ImageFlow / ShutterstockThe germ theory revisited: A noncentric view on infection outcome. Image Credit: ImageFlow / Shutterstock

    Background

    The germ-disease theory, created in the nineteenth century, is a critical medical paradigm claiming that pathogenic microbes cause infectious diseases. However, this explanation is microorganism-centric, failing to explain varying disease severity and symptomatic profiles among individuals. While the microorganism is necessary to produce illness, it cannot solely determine the infection outcome. As a result, the theory must consider the host’s status fluctuations, which considerably impact infection outcomes.

    Recent research questions the theory, giving rise to the full-blown host theory, which holds that infectious illnesses are caused by inherited or acquired immunodeficiencies in the host. According to this hypothesis, viruses are passive environmental triggers, and disease development results from pre-existing host immunodeficiencies. These inadequacies can be covert or overt, depending on diagnostic procedures used to identify critical diseases.

    About the review

    In the present review, researchers investigated the relative relevance of pathogenic microbes and hosts in determining infection outcomes, revealing a non-centric perspective that acknowledges essential roles for both the pathogenic microorganism and the host in defining infection outcomes.

    Pathogens and virulence

    Pathogens are germs that can cause illness among immunocompetent and healthy hosts; nevertheless, asymptomatic carriership occurs when pathogens infect or colonize hosts without causing symptoms. Examples include Helicobacter pylori and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can cause asymptomatic infections in 40% to 80% of cases. Mycobacterium tuberculosis is the most prominent example of pathogens producing asymptomatic carriership, with one-fourth of the worldwide human population latently infected but exhibiting no symptoms of illness.

    Examples demonstrating the evolved ability of S. pyogenes to promote disease in immunocompetent individuals. (A) The surface M protein recruits human C4BP to inhibit complement opsonization (C3b) of the bacterial surface. (B) Secreted streptokinase (SK) binds to human Plg, which causes a conformational change of Plg into a plasmin (Pl) active state. (C) The secreted endoglycosidase EndoS inactivates effector functions of IgG by cleaving off N-glycans from the Fc-region. (D) Secreted superantigen (SAg) causes antigen-independent T cell activation by cross-linking the TCR with HLA-II on antigen presenting cells (APC). SAgs have different affinity for different fully functional HLA-II haplotypes. (E) The STING responds to S. pyogenes-derived c-di-AMP to induce transcription of the interferon β gene, which is inhibited by the enzymatic activity of bacterial NADase. Human STING and S. pyogenes NADase exhibit polymorphisms affecting their relative ability to respond to c-di-AMP and to suppress interferon transcription, respectively.Examples demonstrating the evolved ability of S. pyogenes to promote disease in immunocompetent individuals. (A) The surface M protein recruits human C4BP to inhibit complement opsonization (C3b) of the bacterial surface. (B) Secreted streptokinase (SK) binds to human Plg, which causes a conformational change of Plg into a plasmin (Pl) active state. (C) The secreted endoglycosidase EndoS inactivates effector functions of IgG by cleaving off N-glycans from the Fc-region. (D) Secreted superantigen (SAg) causes antigen-independent T cell activation by cross-linking the TCR with HLA-II on antigen presenting cells (APC). SAgs have different affinity for different fully functional HLA-II haplotypes. (E) The STING responds to S. pyogenes-derived c-di-AMP to induce transcription of the interferon β gene, which is inhibited by the enzymatic activity of bacterial NADase. Human STING and S. pyogenes NADase exhibit polymorphisms affecting their relative ability to respond to c-di-AMP and to suppress interferon transcription, respectively.

    In contrast, opportunistic microbes cannot cause illness in usual settings but can be pathogenic in the case of compromised host steady-state conditions. For example, Clostridium difficile, a spore-forming bacteria, can cause symptomatic illness when treated with antibiotic medications, which reduces the microbiota and allows Clostridium difficile germination to develop a footing. Commensal Candidal fungi can also cause illness in regular settings, but only in the case of immunosuppression, as observed in individuals with HIV-associated immunodeficiency syndrome (AIDS).

    Virulence, a pathogen’s capacity to generate illness symptoms or pathology, is vital to infection outcomes. According to evolutionary theory, a pathogen’s Darwinian fitness is often maximized at an intermediate degree of virulence, resulting in fitness costs and benefits. This idea gains support by controlled laboratory tests and epidemiological research on human illnesses such as AIDS.

    Host-pathogenic microbe interactions and genetic variability

    Streptococcus pyogenes, a bacterium often present in humans, can cause asymptomatic carriership and symptomatic illnesses such as septic shock and necrotizing infections in soft tissues. Streptococcus pyogenes’ surface M proteins are polymorphic virulence factors that impart phagocytic resistance and prevent complement opsonization, recruiting the serum C4b-binding protein (C4BP) and enabling, allowing rapid bacterial proliferation in blood.

    A secreted Streptococcus pyogenes protein, streptokinase, preferentially binds with and stimulates human plasminogen (Plg), promoting proteolytic actions and bacterial spread. Transgenic mice infection revealed the importance of this relationship in virulence, revealing that Streptococcus pyogenes activates fibrinolytic pathways to cause illness.

    The association of bacterial virulence characteristics with the genetic diversity of the host is critical. Superantigens (SAgs) of streptococcal species form cross-links with T-cell receptors (TCRs) to human major histocompatibility complex (MHC) class II molecules, causing antigen-independent T-lymphocyte activation. Fully functional human leukocyte antigen II (HLA-II) variations considerably affect infection outcomes. Type I interferon (IFN) signaling protects Streptococcus pyogenes-infected mice against host-damaging inflammation.

    Uncommon mutations that profoundly impact infection outcomes cause Casanova’s inborn immunity defects. More frequent alleles with lesser effects play a primary role in the phenotypic variance in infection outcomes, maintained by balanced selection. In addition to host genetic diversity, pathogens exhibit enormous genetic variation, and the combination of host and pathogen genotypes considerably impacts disease severity.

    Based on the review findings, microbes have evolved to flourish in extreme conditions such as polar ice, scorching vents, sulfur-acidic lakes, and immunocompetent hosts. Pathogens have developed methods to avoid host defenses, allowing them to infect and produce clinical illness in immunocompetent humans. The review stresses that the host and the pathogen’s genetic diversity can impact infection outcomes, implying that both species play active roles. The researchers’ proposed full-fledged host theory is disproven in favor of a non-centric approach, recognizing crucial roles for the causal bacterium and the host in determining infection outcome.

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  • Mass General Hospital develops clinical decision support tool for mpox diagnosis

    Mass General Hospital develops clinical decision support tool for mpox diagnosis

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    Diagnosing infectious conditions can be challenging. Diagnosis is especially challenging for uncommon and emerging infectious diseases for which there’s limited clinical experience. Nevertheless, successfully identifying patients with infectious diseases, especially communicable ones, is critical, so patients can be isolated to reduce disease spread.

    To address this challenge, investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, recently developed and validated a computer program that can be incorporated into electronic medical record systems to help clinicians diagnose mpox (formerly known as monkeypox).

    The research is published in Infection Control and Healthcare Epidemiology.

    We built a novel decision support tool embedded in the electronic medical record that guides clinicians on crucial features of the physical examination and on important questions to ask patients with possible mpox.”


    Jacob Lazarus, MD, PhD, lead author, physician investigator in the Division of Infectious Diseases within Massachusetts General Hospital’s Department of Medicine, and instructor in Medicine at Harvard Medical School

    The clinical decision support system, called EvalMpox, proved useful in patients presenting to medical care with a rash. Its utility was assessed in 668 patient visits from more than 100 clinical locations across Greater Boston, Nantucket, Martha’s Vineyard, western Massachusetts, and southern New Hampshire.

    EvalMpox guided clinicians in asking patients about potential mpox exposures, about symptoms of mpox, and in performing a physical examination to look for the characteristic mpox rash. EvalMpox was then able to use these answers to classify a patient as “likely to have mpox” or “unlikely to have mpox.”

    The investigators found that the patients deemed likely to have mpox had similar characteristics compared with patients confirmed to have mpox. These patients were then prioritized for testing, and they were significantly more likely to test positive for mpox than patients deemed unlikely to have mpox.

    “Our program identified nearly all cases of mpox diagnosed in the MGB system during the study period, underscoring the value of clinical decision support tools in assisting clinicians with early identification, isolation, and management of patients with communicable diseases like mpox,” said senior author Erica S. Shenoy, MD, PhD, Chief of Infection Control for Mass General Brigham and an associate professor of Medicine at Harvard Medical School.

    The tool also had a high negative predictive value, meaning that if EvalMpox indicated that a person was low risk for mpox, it was very unlikely that they had the infection. “The tool’s high negative predictive value is also important,” emphasized Dr. Shenoy. “While the importance of early identification and isolation to prevent risk of transmission of disease cannot be overemphasized, we also know that it is critically important to have efficient ways to determine when isolation can be discontinued, and to reassure patients that they are unlikely to have an infection.”

    Similar tools may help to assist clinicians in the identification, evaluation, and management of diverse infectious diseases now and in the future.

    “Leveraging insights gained during the COVID-19 pandemic and the mpox outbreak, we are developing new decision support tools for diagnosing other emerging infections such as Ebola, Lassa Fever, and Marburg Virus Disease, as well as to support evaluation and management of patients with more ‘routine’ infections that impact delivery of healthcare based on requirements for patient isolation,” said Lazarus.

    Source:

    Massachusetts General Hospital

    Journal reference:

    Lazarus, J. E., et al. (2024). Separating the rash from the chaff: novel clinical decision support deployed during the mpox outbreak. Infection Control and Hospital Epidemiology. doi.org/10.1017/ice.2024.51.

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  • Climate change boosts infectious disease spread, hits the vulnerable hardest

    Climate change boosts infectious disease spread, hits the vulnerable hardest

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    An article published in The Journal of Infectious Diseases describes how climate change may influence the transmission efficacy of several vector-, water-, and food-borne infections and to what extent these changes can impact socioeconomically deprived and vulnerable populations.

    Article: Climate Change and Contagion: The Circuitous Impacts From Infectious Diseases. Image Credit: Scott Book / ShutterstockArticle: Climate Change and Contagion: The Circuitous Impacts From Infectious Diseases. Image Credit: Scott Book / Shutterstock

    Background

    Earth’s temperature is increasing gradually due to excessive greenhouse gas emissions. The global 10-year average temperature jumped to 1.15 °C above preindustrial levels in 2022. While climate change can directly impact heat waves, floods, and droughts, it can indirectly influence the transmission potency of many infectious pathogens.

    The contagious nature and epidemic potential of these pathogens can be a potential public health concern, especially for marginalized and vulnerable populations who contribute the least to greenhouse gas emissions but are disproportionately affected by the detrimental effects of climate change.

    Vector-borne infections

    Dengue is a vector-borne infection transmitted to humans via an infected Aedes mosquito bite. Due to increasing rates of urbanization, human mobility, and climate change, more than 50% of the global population is currently at risk of contracting dengue.

    Global warming is predicted to facilitate the abundance and global distribution of dengue vectors (Aedes mosquito). Higher altitudes and temperate regions are predicted to experience higher transmissibility, which can negatively affect naïve populations of these regions because of the absence of pre-existing immunity and equipped healthcare systems.

    West Nile virus (WNV) is also transmitted to humans through infected mosquito bites. Higher ambient temperature can improve WNV fitness by increasing its replication inside mosquitoes, accelerating its growth rate, and reducing intervals between blood meals.

    Spring temperate is a robust predictor of WNV transmission in Europe. Depending on geographic regions and climatic conditions, the risk of WNV infection is predicted to increase by fivefold in Europe during 2040 – 2060. Western Europe is predicted to experience the most significant outbreaks of WNV infections.

    Food-borne infections

    The frequency of food-borne infections caused by Salmonella increases in summer months as temperate conditions facilitate the replication of this bacteria. Higher temperatures and heavy rainfall also influence the temporal and geographic distribution of Campylobacter in Northern Europe.

    The number of Campylobacter cases is predicted to increase by 200-fold by 2100. An extension of the transmission season (summer months), together with other types of climate change, might be responsible for this rise.

    Water-borne infections

    About 1.4 million deaths occur worldwide annually due to illnesses caused by contaminated water, poor sanitation, and lack of basic hygiene in households, schools, and healthcare centers.  

    Climate change has become a leading cause of water-borne infections. Increased global temperature induces water evaporation from oceans and a subsequent increase in atmospheric moisture content. These changes cause heavy rainfall and floods, which in turn contribute to increased outbreaks of water-borne infections.

    It has been estimated that the number of excess deaths due to temperature-attributable enteric infections could range between 10,000 and 75,000 per year by 2050–2065, considering optimistic and pessimistic conditions, respectively.

    A significant expansion of marine bacteria (Vibrio parahaemolyticus and Vibrio vulnificus) habitats in brackish water has been observed in recent years due to ocean warming. These bacterial populations can cause severe gastrointestinal infections and wound infections, which can further progress to more severe outcomes, including necrotizing fasciitis, septicemia, and death.  

    Considering medium to high emission conditions, Vibrio vulnificus population is expected to expand to every US state along the seaboard by 2080. This can lead to a simultaneous increase in infection risks in the coming decades.

    Adaptation to climate change

    Challenges associated with controlling climate change-attributable infection rates can be overcome to some extent by continuous monitoring of epidemic precursors of infections through early warning systems.

    The risk from climate change is determined by climate hazard, vulnerability, and exposure. Novel big data sources can be explored to capture the complex and nonlinear interactions between these factors.

    Smart traps that utilize mosquito sensors with machine learning algorithms and bio-acoustic recordings of live insects can be used to identify indigenous or invasive vector species.

    Detection of community transmission before clinical diagnosis can be achieved through monitoring wastewater pathogens.    

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  • Tuberculosis linked to increased risk of cancer, study finds

    Tuberculosis linked to increased risk of cancer, study finds

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    A population-wide observational study to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) shows an association between tuberculosis (TB) and cancer, with those with current or previous TB more likely to have a diagnosis of a variety of cancers, including lung, blood, gynaecological and colorectal cancers. The study is by Dr Jiwon Kim, National Health Insurance Service, Ilsan Hospital, Goyang, South Korea, and Dr Jinnam Kim, Hanyang University College of Medicine, Seoul, South Korea, and colleagues.

    Despite successful cure of TB being possible, complications can occur at various anatomical sites due to structural or vascular damage, metabolic abnormalities and host inflammatory response. These complications may include an increased risk of cancer, which may be influenced by host tissue and DNA damage, and/or interruption of normal gene repair processes and growth factors present in the blood. In this study, the authors investigated the association between cancer incidence and TB compared with the general population.

    They retrospectively reviewed data from the National Health Insurance Service-National Health Information Database of South Korea between 2010 and 2017. Patients with TB were defined as a those with a disease code for TB entered into the system, or treated with two or more TB drugs for more than 28 days. The control group from the general population was randomly selected in a 1:5 ratios and matched for sex, age, income level, residence, and index year. The authors analysed the incidence of newly diagnosed cancer patients after enrolment (post-TB diagnosis). The primary outcome was the incidence of cancer in patients diagnosed with TB infection in the period 2010-2017 compared with the matched cohort. The secondary outcomes were to investigate the risk factors for cancer incidence in TB patients.

    The final analysis included total of 72,542 patients with TB and 72,542 matched controls. The mean follow-up duration was 67 months (around five-and-a-half years), and the mean age in patients with TB was 62 years.

    Compared with the general population, the incidence of cancer was significantly higher in TB patients: 80% higher for all cancers combined; 3.6 times higher for lung cancer, 2.4 times higher for blood (haematological) cancers); 2.2 times higher for gynaecological cancer; 57% higher for colorectal cancer; 56% higher for thyroid cancer and 55% higher for oesophagus and stomach cancer.

    After adjustment, current smoking (40% increased risk versus non-smokers), heavy alcohol consumption (15% increased risk versus regular alcohol consumption) chronic liver disease (42% increased risk versus no liver diseases) and chronic obstructive pulmonary disease (COPD) (8% increased risk) were also identified as independent risk factors for cancer in people with TB.

    The authors say: “TB is an independent risk factor for cancer, not only lung cancer, but also various site-specific cancers, after adjusting for confounders. Screening and management for cancer should be warranted in patients with TB.“

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  • Research suggests booster doses may be necessary for monkeypox immunity

    Research suggests booster doses may be necessary for monkeypox immunity

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    New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) shows that even in men who receives two doses of mpox vaccine intradermally, their level of antibodies to the virus falls to low or zero within the first few months if they have not received a previous smallpox vaccine.

    The authors, who include Dr Klara Sonden, deputy state epidemiologist of the of Public Health Agency of Sweden and affiliated to Karolinska Institute, Stockholm, Sweden, says that their study shows that booster vaccination may be needed long-term for such individuals, and that scientific evidence is needed for the background to any decisions.

    Since May 2022, an mpox outbreak has emerged globally, spreading mainly among men who have sex with men (MSM). It was classified as a Public Health Emergency of International Concern (PHEIC). In Sweden, a vaccine against smallpox based on the live Modified Vaccinia Virus Ankara (MVA-BN), has been offered intradermally to risk groups. Intradermal administration means 0.1 ml in the skin, one-fifth of the dose needed for subcutaneous administration. This was used as a dose-saving strategy as supplies were initially limited.

    The vaccine has been shown to be efficacious in studies using real-world data from the 2022 and onward outbreak among MSM, with limited number of breakthrough infections and milder disease reported when breakthrough infections occur so far. The aim of this cohort study was to assess dynamics of, and factors affecting neutralizing antibodies against mpox virus (MPXV) following MVA-BN vaccination.

    A total of 100 MSM attending the sexual health clinic “Venhälsan”, Stockholm, Sweden, eligible to receive the vaccine MVA-BN were included in the study. Following the initial serum sample drawn before dose 1, serum samples were further collected before dose 2, and 28 days and three months after the second dose. These samples were tested to establish titers (levels) of MPXV-neutralising antibodies. Titers were compared in individuals with or without previous smallpox vaccination and patients with past natural infection were included as positive controls.

    10 individuals were of uncertain status regarding smallpox vaccination (due to being born in many different countries in the time period 1977-1980 when vaccination was de-escalated globally) and 23 individuals were previously smallpox vaccinated. The other 67 individuals had no history of smallpox vaccination.

    A total of 312 samples from four time points from the 100 individuals included in the study were analyzed. In addition to the study population, anonymized age and sex matched controls from blood donors were included as negative controls (n=20) and previously MPXV-infected individuals as positive controls (n=20). The controls gave one blood sample each.

    Within the study group, previous smallpox vaccination was associated with significantly higher antibody titers, and 15/23 of these individuals had pre-existing neutralising antibodies (ie, the B-cell memory was still present thanks to their previous smallpox vaccination).

    Among those without prior smallpox vaccination, fewer than half of the group showed any detectable neutralizing antibodies at all 28 days after the second vaccination, with those who did exhibit responses having a median titer (standard unit of measurement of antibodies) of 20. In contrast, for previously vaccinated individuals, the median titer 28 days after a single dose of the MVA-BN vaccine was 40.

    The authors say: “Our findings corroborate other studies showing that mpox vaccination results in neutralising antibodies only in a proportion of vaccinees, and that a significant decline occurs already during the first month post-vaccination Immunity after previous MPXV infection mounts a higher and more robust neutralising response. In conclusion, the findings merits the study of booster doses.“

    They continue: “Our results indicate a rapid decline in neutralising antibodies after two doses and are in line with other recent studies. These results, together with the continued spread of mpox in MSM populations in Europe has prompted the consideration of a booster dose. Such a recommendation needs to be based on scientific evidence. However, as far as we know, no clinical trial has studied or is studying a 3rd MVA-BN dose (from an analysis of clinicaltrials.gov March 2024), but a booster dose is common practice for inactivated vaccines. The MVA-BN is a live, non-replicating vaccine and therefore likely equivalent to an inactivated vaccine. Studies are essential to inform public health policy, and the largest STI clinic in Sweden is planning to perform a randomised clinical trial of a booster dose with immunological parameters as the primary outcome in the comparison with those who have had the two doses of the regular full 0.5 subcutaneous dose (sc) (0.5ml), two doses of the dose-saving intradermal dose (id) (0.1ml), or one dose sc/one dose id, and those with no booster dose.”

    They add that despite this, the Mpox cases in Sweden have been few and mostly imported during 2023 (12 cases) and 2024 (5 cases) and the vast majority have been among unvaccinated individuals. Data collection is ongoing regarding the occurrence of breakthrough infections in Sweden. Breakthrough cases have been reported in the scientific literature among individuals that have received different vaccination strategies (i.e. sc/sc, id/sc, id/id) (Hazra et al).

    The results presented here indicate that long-term protective immunity might need a booster dose for its maintenance. Since the current situation regarding mpox in Sweden is stable with minimal transmission any change in policy should be backed by results from clinical trials. Currently we will focus on finding unvaccinated individuals who are at risk of getting mpox and offer them vaccination, and we believe that this as well as the previously administered vaccinations will contribute to lowering the risk for new outbreaks of mpox in Sweden in future.”


    Dr. Klara Sonden, deputy state epidemiologist

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