This study investigated the impact of antibiotic eradication of primary Salmonella infection on protection against recurrent infection using a mouse model. The study found that early eradication of primary infection with antibiotics at day 5 or day 20 still provided protection against secondary infection, as shown by significantly lower bacterial loads and survival after challenge. Depletion of CD4+ or CD8+ T cells alone or together did not reduce this protection, indicating these cells are not directly responsible. However, early infection eradication still primed robust anti-Salmonella antibody responses, especially IgG levels, suggesting antibodies may mediate protection against recurrent infection after early clearance of primary Salmonella.
Nowadays, there is a demand for novel
drugs to prevent these infections and the emergence
from mutation of microorganisms. Given the rising
incidence of resistance to synthetic antibiotics and in
light of the rising costs of medicines it is well-timed
to search for natural products such as plant derived
antimicrobial drugs to reduce the resistance of
microorganisms. Pandan (Pandanus amaryllifolius),
in addition to synthetic alternatives, has the potential
of antibacterial activity. The antibacterial properties of
established. For that reason, the research proponents
of this study aims to assess the antibacterial properties
of pandan with the end view of providing low cost
of medications and the prevention of resistance. This research analyzed the in vitro activity of pandan
leaves crude extract against bacterial isolates such as
Staphylococcus aureus
ATCC 25923, Escherichia coli
ATCC 25922 and
Pseudomonas aeruginosa
ATCC 27853.
About 1 kilogram of freshly collected pandan leaves
was subjected to water distillation and the filtrate
was concentrated using rotary evaporator. The crude
extract was then used for the phytochemical analysis.
The Minimum Inhibitory Concentration (MIC) and
Minimum Bactericidal Concentration (MBC) of pandan
against the said microorganisms were examined. This
study also determined the stability of pandan as to pH
and temperature.
Infectious diseases result from pathogenic microorganisms like viruses, bacteria, fungi and parasites. They can be transmitted between individuals through various pathways like physical contact. Non-infectious diseases have causes like genetic disorders, environmental factors and lifestyle choices. They cannot be transmitted between individuals. The immune system usually clears infections, resulting in immunity. However some pathogens can evade immunity and cause life-long infections like HIV.
Doctrine about infection. Pathogenicity & virulence of Bacteria. Development ...Eneutron
This document discusses the key concepts of infection and infectious disease. It defines infection as the penetration of a pathogenic microorganism into a host organism, which can lead to an infectious process and potentially an infectious disease. The main factors required for an infection to develop are the presence of a pathogen, a susceptible host, and a site of entry. Pathogenicity and virulence refer to a microbe's ability to cause disease and the intensity of disease caused. Bacteria exhibit several virulence factors including toxins, enzymes, and adhesins that facilitate adhesion, colonization, invasion and damage of host tissues. Infectious diseases progress through distinct phases and can be classified based on factors like duration, localization, and origin of the
The document discusses microbiology and infectious diseases. It provides an overview of key concepts including the host-agent-environment model of infection, types of host defenses, the hierarchy of microbes from smallest to largest, how microbes are distributed, and the world from a microbe's perspective of surviving and multiplying. It also summarizes common ways of clinically categorizing microbes, stages of infectious disease, criteria for diagnosing infection, bacterial structures, and mechanisms of pathogenesis including virulence factors and toxins.
Human genetic susceptibility to mycobacterium tuberculosis 1Shweta Kaul
complete guide to the basics and all the guides for the human genetic susceptibility to mycobacterium tuberculosis for both masters and bachelors. This presentation includes the future perspectives and all the genes involved that had been identified till date for the disease susceptibility.
The document discusses infectious diseases, which are clinically evident illnesses caused by pathogenic agents like viruses, bacteria, fungi, or parasites. These diseases can be transmitted between individuals through various pathways like physical contact or contaminated objects. Non-infectious diseases are also discussed, which are not caused by pathogens and cannot be transmitted between people. They may be due to genetic, environmental, or lifestyle factors.
Antiviral Effects of Beta Lactoglobulin against Avian Influenza Virusijtsrd
Introduction The avian virus is an Influenza A virus that spread widely among human through direct or indirect contact with infected birds or poultry. But a totally new pandemic of avian virus those are becoming resistant to drugs by changing their genomes may be prevented by antiviral medicines and vaccines. Objective For this purpose ß lactoglobulin is esterified with various alcohols over different circumstances like acidity, protein intentness, water substance, time, temperature, etc. Methodology Methylated ß lactoglobulin provides antiviral activities against human flu infection subtype H3N2, subtype H1N1, and subtype H5N1. The impact of this study is viral HA Hemagglutinin action is repressed by the imposition of different convergences of MET BLG depending upon their distinctive concentration. Result A large number of positive charges on the MET BLG can disrupt the electrostatic intuitive inside hem agglutinin subunits that influences its soundness and movement, lessens its capacity to intertwine and restraints its contamination power. But HA is not the unique factor that decides the viral virulence and infectivity of the virus. Conclusion A different result shows that a higher incubation time increases the antiviral activity of MET BLG. Sadia Afrin | Rezwan Ahmed Mahedi | Mimona Akter "Antiviral Effects of Beta-Lactoglobulin against Avian Influenza Virus" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-1 , December 2020, URL: https://www.ijtsrd.com/papers/ijtsrd38098.pdf Paper URL : https://www.ijtsrd.com/biological-science/microbiology/38098/antiviral-effects-of-betalactoglobulin-against-avian-influenza-virus/sadia-afrin
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It has infected humans for hundreds of thousands of years and was a major cause of death in the 18th-19th centuries. While vaccines and drugs were developed in the early 20th century, cases began rising again in the 1980s due to factors like HIV/AIDS and immigration from high prevalence countries. M. tuberculosis is spread through airborne droplets when infected people cough, sneeze or speak. It typically infects the lungs but can spread throughout the body. The bacterium is able to survive inside immune cells called macrophages. A proper immune response is needed to contain the infection, involving the activation of macrophages and formation of granulomas. Def
Nowadays, there is a demand for novel
drugs to prevent these infections and the emergence
from mutation of microorganisms. Given the rising
incidence of resistance to synthetic antibiotics and in
light of the rising costs of medicines it is well-timed
to search for natural products such as plant derived
antimicrobial drugs to reduce the resistance of
microorganisms. Pandan (Pandanus amaryllifolius),
in addition to synthetic alternatives, has the potential
of antibacterial activity. The antibacterial properties of
established. For that reason, the research proponents
of this study aims to assess the antibacterial properties
of pandan with the end view of providing low cost
of medications and the prevention of resistance. This research analyzed the in vitro activity of pandan
leaves crude extract against bacterial isolates such as
Staphylococcus aureus
ATCC 25923, Escherichia coli
ATCC 25922 and
Pseudomonas aeruginosa
ATCC 27853.
About 1 kilogram of freshly collected pandan leaves
was subjected to water distillation and the filtrate
was concentrated using rotary evaporator. The crude
extract was then used for the phytochemical analysis.
The Minimum Inhibitory Concentration (MIC) and
Minimum Bactericidal Concentration (MBC) of pandan
against the said microorganisms were examined. This
study also determined the stability of pandan as to pH
and temperature.
Infectious diseases result from pathogenic microorganisms like viruses, bacteria, fungi and parasites. They can be transmitted between individuals through various pathways like physical contact. Non-infectious diseases have causes like genetic disorders, environmental factors and lifestyle choices. They cannot be transmitted between individuals. The immune system usually clears infections, resulting in immunity. However some pathogens can evade immunity and cause life-long infections like HIV.
Doctrine about infection. Pathogenicity & virulence of Bacteria. Development ...Eneutron
This document discusses the key concepts of infection and infectious disease. It defines infection as the penetration of a pathogenic microorganism into a host organism, which can lead to an infectious process and potentially an infectious disease. The main factors required for an infection to develop are the presence of a pathogen, a susceptible host, and a site of entry. Pathogenicity and virulence refer to a microbe's ability to cause disease and the intensity of disease caused. Bacteria exhibit several virulence factors including toxins, enzymes, and adhesins that facilitate adhesion, colonization, invasion and damage of host tissues. Infectious diseases progress through distinct phases and can be classified based on factors like duration, localization, and origin of the
The document discusses microbiology and infectious diseases. It provides an overview of key concepts including the host-agent-environment model of infection, types of host defenses, the hierarchy of microbes from smallest to largest, how microbes are distributed, and the world from a microbe's perspective of surviving and multiplying. It also summarizes common ways of clinically categorizing microbes, stages of infectious disease, criteria for diagnosing infection, bacterial structures, and mechanisms of pathogenesis including virulence factors and toxins.
Human genetic susceptibility to mycobacterium tuberculosis 1Shweta Kaul
complete guide to the basics and all the guides for the human genetic susceptibility to mycobacterium tuberculosis for both masters and bachelors. This presentation includes the future perspectives and all the genes involved that had been identified till date for the disease susceptibility.
The document discusses infectious diseases, which are clinically evident illnesses caused by pathogenic agents like viruses, bacteria, fungi, or parasites. These diseases can be transmitted between individuals through various pathways like physical contact or contaminated objects. Non-infectious diseases are also discussed, which are not caused by pathogens and cannot be transmitted between people. They may be due to genetic, environmental, or lifestyle factors.
Antiviral Effects of Beta Lactoglobulin against Avian Influenza Virusijtsrd
Introduction The avian virus is an Influenza A virus that spread widely among human through direct or indirect contact with infected birds or poultry. But a totally new pandemic of avian virus those are becoming resistant to drugs by changing their genomes may be prevented by antiviral medicines and vaccines. Objective For this purpose ß lactoglobulin is esterified with various alcohols over different circumstances like acidity, protein intentness, water substance, time, temperature, etc. Methodology Methylated ß lactoglobulin provides antiviral activities against human flu infection subtype H3N2, subtype H1N1, and subtype H5N1. The impact of this study is viral HA Hemagglutinin action is repressed by the imposition of different convergences of MET BLG depending upon their distinctive concentration. Result A large number of positive charges on the MET BLG can disrupt the electrostatic intuitive inside hem agglutinin subunits that influences its soundness and movement, lessens its capacity to intertwine and restraints its contamination power. But HA is not the unique factor that decides the viral virulence and infectivity of the virus. Conclusion A different result shows that a higher incubation time increases the antiviral activity of MET BLG. Sadia Afrin | Rezwan Ahmed Mahedi | Mimona Akter "Antiviral Effects of Beta-Lactoglobulin against Avian Influenza Virus" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-1 , December 2020, URL: https://www.ijtsrd.com/papers/ijtsrd38098.pdf Paper URL : https://www.ijtsrd.com/biological-science/microbiology/38098/antiviral-effects-of-betalactoglobulin-against-avian-influenza-virus/sadia-afrin
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It has infected humans for hundreds of thousands of years and was a major cause of death in the 18th-19th centuries. While vaccines and drugs were developed in the early 20th century, cases began rising again in the 1980s due to factors like HIV/AIDS and immigration from high prevalence countries. M. tuberculosis is spread through airborne droplets when infected people cough, sneeze or speak. It typically infects the lungs but can spread throughout the body. The bacterium is able to survive inside immune cells called macrophages. A proper immune response is needed to contain the infection, involving the activation of macrophages and formation of granulomas. Def
Antibiotics
History and development of antibiotics
Decline of antibiotics
Bacteriophage: nature’s most abundant antibiotics
Phage specificity, resistance, transduction, lysis
Emergence of phages
Phage Case studies
Challenges to mainstream commercialization
This document discusses various immunodeficiencies and immunotherapies. It covers:
1. The main types of immunodeficiencies including deficiencies of B cells, T cells, combined deficiencies, complement deficiency, and defects in phagocytes.
2. Common immunodeficiency diseases like X-linked agammaglobulinemia, common variable immunodeficiency, and severe combined immunodeficiency.
3. Immunotherapies for treating immunodeficiencies including immunoglobulin injections, bone marrow transplantation, antiviral drugs, immunostimulants, and vaccines.
This document discusses how whole genome sequencing (WGS) of Mycobacterium tuberculosis has improved understanding of drug resistant tuberculosis (TB). WGS has identified specific mutations that cause resistance to classical and new antitubercular drugs. It has also revealed how resistance evolves within patients and spreads between patients. Clinical applications of WGS include rapid detection of drug resistance and tracking of TB outbreaks. However, challenges remain in applying WGS to improve TB control and diagnosis.
epidemiology reservoir & incubation periodaram mustafa
Reservoirs of infectious diseases include humans, animals, arthropods, soil, and other substances where infectious agents live and multiply. There are different types of reservoirs such as human carriers like incubatory or convalescent carriers, animal reservoirs like cattle and sheep, soil reservoirs like tetanus, and arthropod reservoirs like mosquitoes. The incubation period is the time between infection and symptoms appearing, and can vary based on host resistance, the infectious agent, and route of infection. It provides advantages for clinical diagnosis/treatment and implementing preventive public health measures.
This document describes a study that used gene expression profiling to identify early host responses to exposure to various biological threat agents (BTAs). Researchers exposed human immune cells in vitro to bacteria, viruses, and toxins. They found unique gene expression patterns for each pathogen, even at early time points when symptoms are indistinguishable. They confirmed some in vitro findings using nonhuman primates exposed to Bacillus anthracis or Staphylococcal enterotoxin B. The researchers conclude that host gene expression has potential as an early diagnostic tool for BTA exposure.
Bio303 Lecture Three: New Foes, Emerging InfectionsMark Pallen
This document outlines the lectures in a course on global health and emerging infections. The first three lectures discuss existing threats like malaria, tuberculosis, and leprosy. The third lecture focuses on new threats posed by emerging infections and examines case studies of SARS, pandemic flu, and a 2011 E. coli outbreak in Germany. The fourth lecture discusses disease eradication efforts for smallpox and current efforts for polio and guinea worm. The fifth lecture provides an overview of infectious disease diagnosis in clinical microbiology laboratories.
Bio303 Lecture 1 The Global Burden of Infection and an Old Enemy, MalariaMark Pallen
The Global Burden of Infection and an Old Enemy, Malaria. In this lecture I will survey the global burden of infection, including its human and economic costs, and examine the problem of neglected tropical diseases before focusing on one of the most serious infectious threats to humanity: malaria, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection.
See also Bio303 Facebook page
This document discusses antimicrobial resistance and provides several key points:
- Antimicrobial resistance threatens effective treatment of infections and is a serious global public health issue requiring coordinated action.
- Without effective antibiotics, major surgery and cancer treatment would be compromised. Resistant infections also increase healthcare costs.
- In 2016, 490,000 people developed multidrug-resistant tuberculosis globally and resistance is complicating treatment of HIV and malaria.
- Antimicrobial resistance occurs as microbes mutate when exposed to drugs but misuse of antibiotics in people and animals is accelerating this process. Resistant microbes can spread between individuals and countries.
This document summarizes information about Paraprotex, a food supplement that provides anti-parasitic, anti-microbial, and anti-fungal protection. It discusses how parasites and infections are becoming more common worldwide due to factors like diet and immunity. Paraprotex aims to strengthen the immune system and change the body's environment to make it inhospitable for parasites and pathogens. The document also reviews mechanisms of immunity against various biological agents like parasites, fungi, bacteria and viruses. It describes both innate immune responses and acquired immune responses mediated by antibodies and T cells. It discusses how different pathogens elicit distinct immune responses and how parasites have evolved strategies for evading the immune system.
Important emerging bacterial zoonotic infections affecting the immunocompromi...Areesha Ahmad
Immunocompromised individuals are at high risk of infection from emerging zoonotic bacterial diseases. These diseases are transmitted through various routes of exposure including fecal-oral, direct animal contact, outdoor activities, and animal bites or scratches. Major categories of infectious agents include enteric infections from Salmonella, Campylobacter, E. coli O157, Yersinia, and Listeria. Respiratory infections from Bordetella, mycobacteria, and Rhodococcus are also important. Vector-borne diseases such as Bartonella and zoonotic diseases transmitted through animal bites including Pasteurella and Mycobacterium can also affect immunocompromised persons. Adopting proper hygiene practices, vacc
This document discusses the treatment of infections, including antimicrobial therapy and adjuvant therapies. It covers selecting appropriate antimicrobial agents based on the infecting organism and patient factors. The mechanisms of action, pharmacokinetics, and resistance patterns of various classes of antibacterial agents such as beta-lactams, macrolides, and lincosamides are described. Factors contributing to antimicrobial resistance and strategies to prevent resistance are also addressed.
The most likely reason we get sick when the virus mutates is because we do not have a large pool of memory cells and antibodies which recognize the new shapes (antigens) on the surface of the mutated virus. When the virus mutates, it changes the shape of proteins on its surface like hemagglutinin. Our immune system has memory of previous shapes it has encountered, but not the new mutated shapes. Therefore, we are susceptible to infection by the new virus strain.
This document summarizes research on helminth infections and their effects on host immune regulation. It discusses how helminths compromise immunity to protect the host from immunopathology, leading to an immunoregulated state. Chronic infections induce antigen-specific T cell hyporesponsiveness correlated with regulatory cytokines and cells. Deficient acquired immunity fails to clear infections or protect against reinfection. The document examines regulatory cell populations and mechanisms, as well as impacts on vaccine responses and the hygiene hypothesis. Mouse models demonstrate Th2 polarization and regulatory responses to helminths like Schistosoma mansoni.
This document provides an overview of infectious diseases and the immune system. It discusses the innate and adaptive immune response, key components of innate immunity like soluble and cellular factors, and adaptive responses involving B cells and T cells. It also summarizes various clinical pathogens including bacteria, viruses, fungi and parasites; diagnostic approaches; antimicrobial mechanisms of action; and important antimicrobial drug classes.
The document discusses current advancements in parasite treatment and control, including vaccines, DNA/RNA technology, and other methods. It describes different types of vaccines including attenuated, killed, sub-unit, toxoid, and DNA vaccines. Effectiveness depends on understanding the parasite's biology and life cycle. DNA/RNA technology could prove useful by targeting unique epigenetic pathways in parasites. Overall the document provides an overview of recent developments in parasite vaccines and control methods.
Vaccines are less likely than drugs to induce resistance in pathogens for two key reasons: timing and multiplicity of targets. Vaccines are administered prophylactically before infection, limiting pathogen population size and diversity, whereas drugs are given therapeutically after symptoms when the pathogen population is larger. Additionally, vaccines target multiple antigen sites across populations through herd immunity, whereas drugs typically have fewer targets. While resistance can evolve to some vaccines over long periods of use through natural evolution or vaccine-driven selection, vaccines remain the most effective solution to combating drug resistance.
This document summarizes a study that examined the relationship between intestinal inflammation, dysbiosis (imbalances in the gut microbiome), and bacterial invasion in murine models of ileal Crohn's disease. The researchers found that moderate to severe intestinal inflammation induced by Toxoplasma gondii infection or high-dose indomethacin caused dysbiosis characterized by a shift from Gram-positive to Gram-negative bacteria and reduced microbial diversity. This dysbiosis was accompanied by invasion of mucosal tissues by adherent-invasive E. coli, similar to what is seen in human Crohn's disease. In contrast, mild intestinal inflammation induced by Giardia muris did not result in dysbiosis or bacterial
The document defines various terms related to infections, including infection, host, carrier, incubation period, and more. It then describes different types of infections such as bacterial, viral, parasitic and fungal infections. Specific examples of bacterial infections involving different parts of the body are provided, such as skin and soft tissue infections, gastrointestinal infections, respiratory tract infections, and others. Common respiratory infections like pneumonia and their classification are also defined.
Microbes and vectors swim in the evolutionary stream, and they swim faster than we do. Bacteria reproduce every 30 minutes. For them, a millennium is compressed into a fortnight. They are fleet afoot, and the pace of our research must keep up with them, or they will overtake us. Microbes were here on earth 2 billion years before humans arrived, learning every trick for survival, and it is likely that they will be here 2 billion years after we depart ......
This document discusses human parasite vaccines. It begins by explaining what vaccines do in stimulating the host's protective immune response. Developing effective parasite vaccines faces challenges including not fully understanding the parasite's life cycle and which stages elicit a protective immune response. Effective vaccines must produce long-lasting protection without boosting and be low-cost, stable, and safe. Progress has been limited for parasite vaccines due to parasites' ability to evade the immune system, uncertainty regarding which antigens stimulate protection, and differences between animal models and human immune responses. Major human parasitic diseases discussed include malaria, African sleeping sickness, Chagas disease, leishmaniasis, intestinal protozoa, schistosomiasis, onchocerciasis
Prolonged or improper use of antibiotics for typhoid can lead to long term effects. Antibiotics place selective pressure that can cause resistant strains of Salmonella to emerge and spread. As these resistant bacteria reproduce and share their resistance genes with others, diseases may persist longer with worse symptoms. This can eventually lead to incurable infections if resistance grows. Careful and appropriate antibiotic use under medical guidance can help reduce resistance development. Vaccines may also slow bacterial evolution by strengthening the body's natural immunity.
Specific prophylaxis and therapy of infectious diseases. Vaccines & toxoidesEneutron
Vaccines provide protection against infectious diseases by exposing individuals to antigens from pathogens in a way that does not cause disease. There are several types of vaccines, including live attenuated vaccines which use weakened live pathogens, and inactivated vaccines which use killed pathogens. Live vaccines typically produce stronger and longer-lasting immunity but carry some risk, while inactivated vaccines are safer but may require booster doses to maintain protection. Both vaccine types aim to stimulate the immune system's memory response to future pathogens, protecting individuals and populations through herd immunity when widely adopted.
Antibiotics
History and development of antibiotics
Decline of antibiotics
Bacteriophage: nature’s most abundant antibiotics
Phage specificity, resistance, transduction, lysis
Emergence of phages
Phage Case studies
Challenges to mainstream commercialization
This document discusses various immunodeficiencies and immunotherapies. It covers:
1. The main types of immunodeficiencies including deficiencies of B cells, T cells, combined deficiencies, complement deficiency, and defects in phagocytes.
2. Common immunodeficiency diseases like X-linked agammaglobulinemia, common variable immunodeficiency, and severe combined immunodeficiency.
3. Immunotherapies for treating immunodeficiencies including immunoglobulin injections, bone marrow transplantation, antiviral drugs, immunostimulants, and vaccines.
This document discusses how whole genome sequencing (WGS) of Mycobacterium tuberculosis has improved understanding of drug resistant tuberculosis (TB). WGS has identified specific mutations that cause resistance to classical and new antitubercular drugs. It has also revealed how resistance evolves within patients and spreads between patients. Clinical applications of WGS include rapid detection of drug resistance and tracking of TB outbreaks. However, challenges remain in applying WGS to improve TB control and diagnosis.
epidemiology reservoir & incubation periodaram mustafa
Reservoirs of infectious diseases include humans, animals, arthropods, soil, and other substances where infectious agents live and multiply. There are different types of reservoirs such as human carriers like incubatory or convalescent carriers, animal reservoirs like cattle and sheep, soil reservoirs like tetanus, and arthropod reservoirs like mosquitoes. The incubation period is the time between infection and symptoms appearing, and can vary based on host resistance, the infectious agent, and route of infection. It provides advantages for clinical diagnosis/treatment and implementing preventive public health measures.
This document describes a study that used gene expression profiling to identify early host responses to exposure to various biological threat agents (BTAs). Researchers exposed human immune cells in vitro to bacteria, viruses, and toxins. They found unique gene expression patterns for each pathogen, even at early time points when symptoms are indistinguishable. They confirmed some in vitro findings using nonhuman primates exposed to Bacillus anthracis or Staphylococcal enterotoxin B. The researchers conclude that host gene expression has potential as an early diagnostic tool for BTA exposure.
Bio303 Lecture Three: New Foes, Emerging InfectionsMark Pallen
This document outlines the lectures in a course on global health and emerging infections. The first three lectures discuss existing threats like malaria, tuberculosis, and leprosy. The third lecture focuses on new threats posed by emerging infections and examines case studies of SARS, pandemic flu, and a 2011 E. coli outbreak in Germany. The fourth lecture discusses disease eradication efforts for smallpox and current efforts for polio and guinea worm. The fifth lecture provides an overview of infectious disease diagnosis in clinical microbiology laboratories.
Bio303 Lecture 1 The Global Burden of Infection and an Old Enemy, MalariaMark Pallen
The Global Burden of Infection and an Old Enemy, Malaria. In this lecture I will survey the global burden of infection, including its human and economic costs, and examine the problem of neglected tropical diseases before focusing on one of the most serious infectious threats to humanity: malaria, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection.
See also Bio303 Facebook page
This document discusses antimicrobial resistance and provides several key points:
- Antimicrobial resistance threatens effective treatment of infections and is a serious global public health issue requiring coordinated action.
- Without effective antibiotics, major surgery and cancer treatment would be compromised. Resistant infections also increase healthcare costs.
- In 2016, 490,000 people developed multidrug-resistant tuberculosis globally and resistance is complicating treatment of HIV and malaria.
- Antimicrobial resistance occurs as microbes mutate when exposed to drugs but misuse of antibiotics in people and animals is accelerating this process. Resistant microbes can spread between individuals and countries.
This document summarizes information about Paraprotex, a food supplement that provides anti-parasitic, anti-microbial, and anti-fungal protection. It discusses how parasites and infections are becoming more common worldwide due to factors like diet and immunity. Paraprotex aims to strengthen the immune system and change the body's environment to make it inhospitable for parasites and pathogens. The document also reviews mechanisms of immunity against various biological agents like parasites, fungi, bacteria and viruses. It describes both innate immune responses and acquired immune responses mediated by antibodies and T cells. It discusses how different pathogens elicit distinct immune responses and how parasites have evolved strategies for evading the immune system.
Important emerging bacterial zoonotic infections affecting the immunocompromi...Areesha Ahmad
Immunocompromised individuals are at high risk of infection from emerging zoonotic bacterial diseases. These diseases are transmitted through various routes of exposure including fecal-oral, direct animal contact, outdoor activities, and animal bites or scratches. Major categories of infectious agents include enteric infections from Salmonella, Campylobacter, E. coli O157, Yersinia, and Listeria. Respiratory infections from Bordetella, mycobacteria, and Rhodococcus are also important. Vector-borne diseases such as Bartonella and zoonotic diseases transmitted through animal bites including Pasteurella and Mycobacterium can also affect immunocompromised persons. Adopting proper hygiene practices, vacc
This document discusses the treatment of infections, including antimicrobial therapy and adjuvant therapies. It covers selecting appropriate antimicrobial agents based on the infecting organism and patient factors. The mechanisms of action, pharmacokinetics, and resistance patterns of various classes of antibacterial agents such as beta-lactams, macrolides, and lincosamides are described. Factors contributing to antimicrobial resistance and strategies to prevent resistance are also addressed.
The most likely reason we get sick when the virus mutates is because we do not have a large pool of memory cells and antibodies which recognize the new shapes (antigens) on the surface of the mutated virus. When the virus mutates, it changes the shape of proteins on its surface like hemagglutinin. Our immune system has memory of previous shapes it has encountered, but not the new mutated shapes. Therefore, we are susceptible to infection by the new virus strain.
This document summarizes research on helminth infections and their effects on host immune regulation. It discusses how helminths compromise immunity to protect the host from immunopathology, leading to an immunoregulated state. Chronic infections induce antigen-specific T cell hyporesponsiveness correlated with regulatory cytokines and cells. Deficient acquired immunity fails to clear infections or protect against reinfection. The document examines regulatory cell populations and mechanisms, as well as impacts on vaccine responses and the hygiene hypothesis. Mouse models demonstrate Th2 polarization and regulatory responses to helminths like Schistosoma mansoni.
This document provides an overview of infectious diseases and the immune system. It discusses the innate and adaptive immune response, key components of innate immunity like soluble and cellular factors, and adaptive responses involving B cells and T cells. It also summarizes various clinical pathogens including bacteria, viruses, fungi and parasites; diagnostic approaches; antimicrobial mechanisms of action; and important antimicrobial drug classes.
The document discusses current advancements in parasite treatment and control, including vaccines, DNA/RNA technology, and other methods. It describes different types of vaccines including attenuated, killed, sub-unit, toxoid, and DNA vaccines. Effectiveness depends on understanding the parasite's biology and life cycle. DNA/RNA technology could prove useful by targeting unique epigenetic pathways in parasites. Overall the document provides an overview of recent developments in parasite vaccines and control methods.
Vaccines are less likely than drugs to induce resistance in pathogens for two key reasons: timing and multiplicity of targets. Vaccines are administered prophylactically before infection, limiting pathogen population size and diversity, whereas drugs are given therapeutically after symptoms when the pathogen population is larger. Additionally, vaccines target multiple antigen sites across populations through herd immunity, whereas drugs typically have fewer targets. While resistance can evolve to some vaccines over long periods of use through natural evolution or vaccine-driven selection, vaccines remain the most effective solution to combating drug resistance.
This document summarizes a study that examined the relationship between intestinal inflammation, dysbiosis (imbalances in the gut microbiome), and bacterial invasion in murine models of ileal Crohn's disease. The researchers found that moderate to severe intestinal inflammation induced by Toxoplasma gondii infection or high-dose indomethacin caused dysbiosis characterized by a shift from Gram-positive to Gram-negative bacteria and reduced microbial diversity. This dysbiosis was accompanied by invasion of mucosal tissues by adherent-invasive E. coli, similar to what is seen in human Crohn's disease. In contrast, mild intestinal inflammation induced by Giardia muris did not result in dysbiosis or bacterial
The document defines various terms related to infections, including infection, host, carrier, incubation period, and more. It then describes different types of infections such as bacterial, viral, parasitic and fungal infections. Specific examples of bacterial infections involving different parts of the body are provided, such as skin and soft tissue infections, gastrointestinal infections, respiratory tract infections, and others. Common respiratory infections like pneumonia and their classification are also defined.
Microbes and vectors swim in the evolutionary stream, and they swim faster than we do. Bacteria reproduce every 30 minutes. For them, a millennium is compressed into a fortnight. They are fleet afoot, and the pace of our research must keep up with them, or they will overtake us. Microbes were here on earth 2 billion years before humans arrived, learning every trick for survival, and it is likely that they will be here 2 billion years after we depart ......
This document discusses human parasite vaccines. It begins by explaining what vaccines do in stimulating the host's protective immune response. Developing effective parasite vaccines faces challenges including not fully understanding the parasite's life cycle and which stages elicit a protective immune response. Effective vaccines must produce long-lasting protection without boosting and be low-cost, stable, and safe. Progress has been limited for parasite vaccines due to parasites' ability to evade the immune system, uncertainty regarding which antigens stimulate protection, and differences between animal models and human immune responses. Major human parasitic diseases discussed include malaria, African sleeping sickness, Chagas disease, leishmaniasis, intestinal protozoa, schistosomiasis, onchocerciasis
Prolonged or improper use of antibiotics for typhoid can lead to long term effects. Antibiotics place selective pressure that can cause resistant strains of Salmonella to emerge and spread. As these resistant bacteria reproduce and share their resistance genes with others, diseases may persist longer with worse symptoms. This can eventually lead to incurable infections if resistance grows. Careful and appropriate antibiotic use under medical guidance can help reduce resistance development. Vaccines may also slow bacterial evolution by strengthening the body's natural immunity.
Specific prophylaxis and therapy of infectious diseases. Vaccines & toxoidesEneutron
Vaccines provide protection against infectious diseases by exposing individuals to antigens from pathogens in a way that does not cause disease. There are several types of vaccines, including live attenuated vaccines which use weakened live pathogens, and inactivated vaccines which use killed pathogens. Live vaccines typically produce stronger and longer-lasting immunity but carry some risk, while inactivated vaccines are safer but may require booster doses to maintain protection. Both vaccine types aim to stimulate the immune system's memory response to future pathogens, protecting individuals and populations through herd immunity when widely adopted.
Preventive and therapeutic strategies in critically ill patients with highly...Sergio Paul Silva Marin
This document discusses preventive and therapeutic strategies for critically ill patients infected with highly resistant bacteria. It notes that antibiotic resistance is a major global problem, with multidrug-resistant and pandrug-resistant organisms increasingly encountered in healthcare settings. The review focuses on strategies for severely ill ICU patients, who are at high risk of nosocomial infections due to medical advances enabling longer stays. Timely diagnosis and optimized antibiotic treatment are important for managing such infections.
Combating Drug Resistance in The Intensive Care Unit (ICU)Apollo Hospitals
Drug resistance of microbes has become a major challenge in treating ICU patients successfully. There are many factors that contribute to the development of drug resistance, including irrational antibiotic use, lack of antibiotic stewardship programs, and poor infection control practices. Implementing strict antibiotic policies, having responsive microbiology departments, and educating healthcare providers on following clinical guidelines are important first steps to prevent drug resistance. It is also essential to monitor antibiotic use, tailor therapies based on culture results, and withdraw antibiotics appropriately once infections have resolved. A multifaceted approach involving hospitals, healthcare workers, and communities is needed to curb the growing issue of antimicrobial resistance.
The document discusses immunity to fungal infections. It notes that fungi can cause diseases through either a lack of immune recognition or overactivation of the inflammatory response. The immune system uses pattern recognition receptors and innate immune cells like phagocytes to recognize and respond to fungal pathogens. Both resistance mechanisms that limit fungal growth and tolerance mechanisms that limit host damage are important for maintaining immune homeostasis during fungal infections.
A pilot study on effects of vaccination on immunity of broiler chickensAlexander Decker
This document summarizes a pilot study that examined the effects of vaccination on the immunity of broiler chickens challenged with Newcastle disease virus (NDV). Twenty broiler chickens were divided into five groups, with four groups receiving different locally produced NDV vaccines and one unvaccinated control group. When challenged with NDV at five weeks old, the vaccinated groups showed no clinical signs of infection while the unvaccinated group had 100% mortality within 48 hours. This indicates that vaccination is important for preventing and controlling poultry diseases, as maternal immunity alone in young chicks is not sufficient to fight infections. Locally produced vaccines should be encouraged for small farmers to manage viral outbreaks.
1) Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a more severe form of sepsis with profound circulatory, cellular and metabolic abnormalities that increase mortality.
2) For patients with suspected sepsis or septic shock, antimicrobial therapy should be administered as soon as possible, ideally within 1 hour. Empiric broad-spectrum therapy is recommended to cover likely pathogens.
3) Source control through rapid identification and treatment of the infection site is also recommended for patients with sepsis or septic shock.
Seminar pmr726-meningitis and smallpox vaccineFarhan Furreh
Meningitis and smallpox vaccines are discussed. Meningitis is caused by Neisseria meningitidis and there are two main types of meningitis vaccines - polysaccharide and conjugate vaccines. Smallpox was eradicated through vaccination with the smallpox vaccine, which contains live vaccinia virus and provides protection for 3-5 years. Both vaccines have been highly effective in preventing outbreaks and epidemics of their respective diseases.
This document summarizes a study on Acinetobacter species isolated from clinical samples at a tertiary care hospital in Odisha, India. The study found that of 8,749 clinical samples tested, 137 (3%) yielded Acinetobacter species. Most isolates were from pus/swab samples (56.9%) and blood (13.1%). Risk factors for infection included older age, hospitalization, longer stays, comorbidities, and invasive procedures. Many isolates were multidrug-resistant (54.7%) or pan-drug resistant (5.8%), showing high resistance to many antibiotics. However, isolates remained sensitive to imipenem, meropenem, piperacillin/tazobact
The document summarizes information about tuberculosis (TB). It describes TB as affecting mainly the lungs and causing symptoms like cough, weight loss, and fatigue. The causative agent is identified as Mycobacterium tuberculosis bacteria. The pathogenesis involves the bacteria being inhaled and surviving inside immune cells in the lungs, eventually forming nodules that can spread infection. Diagnosis involves tests like chest x-rays and detecting the bacteria in sputum. Treatment consists of a combination of antibiotics taken for several months.
This paper proposes a vaccine-dependent mathematical model to study the transmission dynamics of tuberculosis (TB) epidemics at the population level. The model divides the population into susceptible, latently infected unvaccinated, latently infected vaccinated, actively infected, recovered, and vaccinated classes. The paper proves the existence and uniqueness of a solution to the system of equations that defines the model. It also shows that the infection will die out if the basic reproduction number is less than one. The model could be used to estimate new TB infections and help design prevention and intervention strategies.
- Since 2014, the USDA has confirmed cases of highly pathogenic avian influenza (HPAI) in migratory bird flyways along the Pacific, Central, and Mississippi routes. Wild birds can carry and spread influenza viruses along these routes.
- Avian influenza viruses can infect both domestic and wild birds. While wild birds usually do not get sick, the viruses are highly contagious and can make birds severely ill or kill them.
- The document discusses avian influenza A virus in birds and its transmission through migratory flyways in North America.
Introduction to malaria immunopathogenesis.pptwalealufa
The main impetus for trying to understand immunity to malaria is the need to develop effective malaria vaccines. Despite years of knowing that humans can be immune to malaria the mechanisms underlying this immunity are yet to be properly understood.
This is, in part, attributable to the complexity of the malaria parasite and its life cycle resulting in a complex parasite-host relation.
Pneumonia is a common lung infection that can be caused by bacteria, viruses, fungi or parasites. It results in inflammation and fluid in the alveoli, causing symptoms like cough, chest pain, fever and difficulty breathing. The most common bacterial causes are Streptococcus pneumoniae and atypical bacteria. Pneumonia poses greater risks for elderly people, young children, and those with weakened immune systems. Diagnosis involves tests like chest x-rays and treatment differs based on the identified cause.
This document provides an overview of live bacterial vaccines, focusing on attenuated pathogens and food-related lactic acid bacteria used as vaccine vehicles. It discusses the advantages of live bacterial vaccines, including their mimicry of natural infection and intrinsic adjuvant properties. However, it also outlines some safety concerns, such as the risk of reversion to virulence for attenuated pathogens. The document reviews several examples of attenuated pathogens currently being developed as vaccines, and food-related lactic acid bacteria that have been studied as potential vaccine delivery vehicles due to their generally recognized as safe status. It concludes that while live bacterial vaccines show promise, very few have reached the market due to challenges in developing safe and effective candidates.
This document discusses infections that can occur in organ transplant patients. It notes that over 40,000 organ transplants are performed annually worldwide, with high success rates. However, infections remain a major challenge for transplant recipients. The types and risks of infections vary depending on the transplanted organ and time since transplantation. In the first month after transplant, patients are most at risk for healthcare-associated infections. From 1-6 months, they are susceptible to opportunistic infections like CMV. After 6 months, most patients have well-functioning grafts but some remain at higher risk of infections. Close monitoring and a high index of suspicion are needed to manage infection risks in transplant patients over time.
This document discusses a study examining gender differences in immune biomarkers in active tuberculosis (TB) patients and how these biomarkers correlate with treatment efficacy. The study found that female TB patients had significantly higher levels of CXCL9 and CXCL10, while males had higher levels of PDGF-BB. Antibody levels against TB antigens were also higher in males. Biomarker levels of CXCL9, CXCL10, PDGF-BB, IFNg, and IL-18 decreased substantially over the course of treatment in patients, correlating with treatment success. The results suggest gender differences in immune responses to TB infection and that immune biomarkers may help monitor treatment efficacy.
This document discusses the appropriate use of antibiotics in emergency settings. It begins with an introduction on the need for early empiric antibiotic therapy in some infections. It then outlines the indications and spectrum of activity of commonly used antibiotics for conditions like UTI, meningitis, pneumonia, and soft tissue infections. It emphasizes that delays in administering antibiotics in conditions like meningitis and sepsis are associated with worse outcomes.
1. Original article
Early eradication of persistent Salmonella infection primes
antibody-mediated protective immunity to recurrent infection
Tanner M. Johanns a,b
, Calvin Y. Law a,b
, Lokeshchandra A. Kalekar a,b
, Hope O’Donnell a,b
,
James M. Ertelt a,b
, Jared H. Rowe a,b
, Sing Sing Way a,b,*
a
Department of Pediatrics, University of Minnesota School of Medicine, Center for Infectious Disease and Microbiology Translational Research, USA
b
Department of Microbiology, University of Minnesota School of Medicine, Center for Infectious Disease and Microbiology Translational Research, USA
Received 1 July 2010; accepted 23 November 2010
Abstract
Typhoid fever is a systemic, persistent infection caused by host-specific strains of Salmonella. Although the use of antibiotics has reduced the
complications associated with primary infection, recurrent infection remains an important cause of ongoing human morbidity and mortality.
Herein, we investigated the impacts of antibiotic eradication of primary infection on protection against secondary recurrent infection. Using
a murine model of persistent Salmonella infection, we demonstrate protection against recurrent infection is sustained despite early eradication of
primary infection. In this model, protection is not mediated by CD4þ
or CD8þ
T cells because depletion of these cells either alone or in
combination prior to rechallenge does not abrogate protection. Instead, infection followed by antibiotic-mediated clearance primes robust levels
of Salmonella-specific antibody that can adoptively transfer protection to naı¨ve mice. Thus, eradication of persistent Salmonella infection primes
antibody-mediated protective immunity to recurrent infection.
Ó 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Keywords: Salmonella; Antibiotic treatment; Recurrent infection
1. Introduction
Typhoid fever is a persistent, systemic infection caused by
host-adapted strains of Gram-negative bacteria within the
Salmonella genus. The development and use of antimicrobials
with bactericidal activity against Salmonella has transformed
this once debilitating and often fatal infection into a readily
treatable condition. Unfortunately even with antibiotic therapy,
recurrent disease occurs in 5e15% of individuals [1e4].
Molecular genotyping and phenotyping of Salmonella enterica
serotype Typhi (Salmonella typhi) isolates from individuals with
primary and recurrent infection suggest recurrence may be
caused by re-activation of latent or secondary infection [2,5,6].
However, for individuals living in endemic areas where re-
exposure is essentially unavoidable, protection from recurrent
infection is paramount, while the significance of distinguishing
Salmonella isolates associated with re-activation or secondary
infection appears less relevant.
Regardless of the specific etiology, the clinical symptoms of
recurrent compared with primary infection are less severe and of
shorter duration [7]. Similarly, reduced rates of clinical typhoid
fever and infection relapse have been reported for human
volunteers previously recovered from typhoid compared with
naı¨ve individuals after challenge with virulent Salmonella
[8], and reduced attack rates occur for individuals with prior
Salmonella infection during an outbreak among military
personnel exposed to infected food handlers [9]. These epide-
miologicalfeaturesof human typhoid suggestnaturally-acquired
Salmonella infection confers some protection against secondary
infection.
Protection from recurrent disease triggered by primary
infection is also reproduced in animal models of Salmonella
infection. For example, natural recovery from experimental
typhoid fever protects chimpanzees from fever, bacteremia, and
* Corresponding author. 2001 6th Street SE, Room 3-212, Minneapolis, MN
55455, USA. Tel.: þ1 612 626 2526; fax: þ1 612 626 9924.
E-mail address: singsing@umn.edu (S.S. Way).
1286-4579/$ - see front matter Ó 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.micinf.2010.11.004
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
Microbes and Infection xx (2010) 1e9
www.elsevier.com/locate/micinf
+ MODEL
2. systemic inflammation after secondary challenge with virulent
Salmonella [10]. For mouse typhoid caused by S. enterica
serotype Typhimurium (Salmonella typhimurium) primary
infection with live-attenuated Salmonella mutants confers
a high level of protection against secondary challenge with
virulent Salmonella [11,12]. Thus, animal models of typhoid
infection allow the potential impact of antibiotic treatment in
priming protective immunity to be more precisely character-
ized. In this regard, a recent study reported sharply reduced
protection against recurrent infection after early eradication of
primary infection with virulent Salmonella compared with that
primed by an attenuated Salmonella mutant that causes more
sustained infection [13]. These findings suggest antimicrobial
therapy, while beneficial for curtailing the sequelae of primary
infection, may also blunt the priming of protective immunity
conferred by natural infection. However, the inhe-
rent susceptibility C57BL/6 mice lacking the resistant allele of
Nramp1 to virulent S. typhimurium used in this study required
the eradication of primary infection within two days. Therefore,
the effects of antibiotic-mediated clearance of primary infection
during the later and persistent phase of this infection remain
undefined. In this study, mice containing the resistant allele of
Nramp1 that develop persistent infection with virulent Salmo-
nella were used to investigate the impacts of primary infec-
tion eradication on protection against secondary Salmonella
infection.
2. Materials and methods
2.1. Mice
C57BL/6 and 129SvJ micewere purchased from the National
Cancer Institute. B6.129F1 mice generated by intercrossing
C57BL/6 females with 129SvJ males as a model for persis-
tent infection with virulent Salmonella have been described
[14e16]. All mice were generated and maintained in specific
pathogen-free facilities and used between 6 and 8 weeks of age.
These experiments were conducted under University of Min-
nesota IACUC approved protocols.
2.2. Bacteria, infections, and antibiotic treatment
The virulent S. enterica serotype Typhimurium (S. typhi-
murium) strain, SL1344, has been described [12,17,18]. For
infections, S. typhimurium was grown to log phase in brain heart
infusion (BHI) media at 37
C, washed and diluted with saline
and injected intravenously through the lateral tail vein [16]. The
number of recoverable Salmonella CFUs was quantified by
plating serial dilutions of organ homogenates onto BHI agar
plates. Where indicated, enrofloxacin was added to the drinking
water (2 mg/ml) beginning five or twenty days post-infection.
Mice were withdrawn from antibiotics for at least five days
prior to secondary infection. For rechallenge, 1 Â 104
or
1 Â 106
CFU of SL1344 was injected intravenously. Heat-killed
Salmonella was prepared by resuspending SL1344 in sterile
saline and incubating at 75
C for 60 min, and plating to confirm
the absence of live bacteria as described [19].
2.3. Reagents for cell staining, antibody ELISA, and cell
depletion
Antibodies and other reagents for flow cytometry and
ELISA were purchased from BD Biosciences (San Jose, CA)
or eBioscience (San Diego, CA). For ELISA, flat bottom 96-
well plates were coated with 1.25 Â 107
CFU heat-killed
SL1344 diluted in 0.1 M NaHCO3 and incubated overnight at
4
C. Wells were then blocked with 1% albumin, assayed with
serial dilutions of serum from Salmonella infected mice fol-
lowed by biotinylated anti-mouse isotype specific antibodies,
and developed with streptavidin conjugated to peroxidase and
O-phenylenediamene substrate. For CD4þ
and CD8þ
T cell
depletion, 500 mg of purified anti-mouse CD4 (clone GK1.5)
and/or anti-mouse CD8 (clone 2.43) antibody (BioXCell) were
inoculated intraperitoneally one day prior to Salmonella
infection. For transfer, serum was collected from donor mice,
and transferred intravenously into naı¨ve recipient mice
(350e400 ml/mouse) one day prior to Salmonella infection.
2.4. Statistics
The difference in number of recoverable bacterial CFUs
and survival were evaluated using the Student’s t and log-rank
tests, respectively (GraphPad, Prism Software) with P 0.05
taken as statistically significant.
3. Results
3.1. Protective immunity despite early eradication of
primary Salmonella infection
The reduced severity, shorter duration, and lowered attack
rates of recurrent compared with primary Salmonella infection
in humans suggest natural infection primes some protective
effects against secondary infection [8,9]. To address how erad-
ication of primary infection impacts these protective effects, we
compared the susceptibility against secondary recurrent infec-
tion with virulent Salmonella for mice treated with antibiotics
after primary infection or control mice without primary infec-
tion. We initially enumerated the relative susceptibility for
S. typhimurium-infected mice (104
CFU) treated with enro-
floxacin beginning day 20 after primary infection. Enrofloxacin
is a fluoroquinolone antibiotic, and this dose has been shown to
eradicate systemic Salmonella infection within five to seven
days after administration in the drinking water [13,20]. Using
this approach, highly significant (!50e100-fold) reductions in
recoverable Salmonella were found after secondary challenge
(104
CFU) for mice eradicated of primary infection compared
with control mice without primary Salmonella infection
(Fig. 1A). This reduction in number of recoverable Salmonella
CFUs was not due to residual enrofloxacin because both groups
of mice were treated and withdrawn from this antibiotic in
parallel. Thus, protection against recurrent Salmonella infection
is sustained despite eradication of primary infection.
To investigate if earlier eradication of primary Salmonella
infection would impact protection against recurrent infection, we
2 T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
3. compared the effects of antibiotic initiation beginning day 5
compared with day 20 after primary infection. We found
protection against secondary infection was sustained with eradi-
cation of primary infection beginning day 5, and these protective
effects were indistinguishable compared with mice treated with
antibiotics later (day 20) (Fig. 1B). Importantly, these protective
effects could not be attributed to reduced efficiency of antibiotic
eradication of virulent S. typhimurium that causes persistent
infection in mice containing the resistant allele of Nramp1
because enrofloxacin readily eradicated primary infection within
the first 5e7 days after treatment (Fig. 2).
Additional experiments explored the magnitude of these
protective effects by enumerating survival following secon-
dary infection with a higher dose of virulent S. typhimurium
(106
CFU) that normally causes lethal infection even in mice
containing the resistant allele of Nramp1. These experiments
revealed that eradication of primary infection with antibiotics
beginning day 5 was sufficient to protect mice from lethal
Salmonella infection, while naı¨ve control mice treated with
antibiotics in parallel all succumbed within the first week after
infection (Fig. 3). These protective effects of primary infection
followed by eradication with antibiotics shortly thereafter were
specific to live Salmonella infection because the same dose of
heat-killed Salmonella used for primary infection (104
CFU)
provided no protective effects (Fig. 3). These results demonstrate
primary Salmonella infection even with antibiotic eradication
primes protection against recurrent infection.
3.2. Neither CD4þ
nor CD8þ
T cells directly mediate
protection against recurrent Salmonella infection
T cells are important mediators of host defense against
Salmonella infection because mice with targeted defects in
CD4þ
and CD8þ
T cells show defects in controlling both
primary and secondary infection even with attenuated Salmo-
nella mutant strains [21e26]. However, given the intricate cross-
regulation between T cells and other immune cell subsets, the use
of mice with targeted T cell defects cannot discriminate between
whether these cells are required for priming protection by other
immune mediators or if T cells directly provide protection. To
overcome these limitations and determine the specific require-
ments for CD4þ
and/or CD8þ
T cells in protection against
recurrent Salmonella infection after eradication of primary
infection, we compared the susceptibility of antibiotic-treated
mice following CD4þ
and/or CD8þ
T cell depletion immediately
prior to secondary infection. We found CD4þ
or CD8þ
T cell
Fig. 1. Protection against secondary Salmonella infection despite early eradication of primary infection. A. Number of recoverable Salmonella CFUs in the spleen
and liver day 5 post-secondary challenge (104
CFU) in B6.129F1 mice treated with antibiotics beginning day 20 after primary infection (104
CFU) or control mice
treated with antibiotics in parallel without primary infection. B. Number of recoverable Salmonella CFUs in the spleen and liver day 5 post-secondary challenge
(104
CFU) in B6.129F1 mice treated with antibiotics beginning either day 5 or day 20 after primary infection (104
CFU), or control mice without primary infection.
These results are representative of two independent experiments each containing 3e5 mice per group. Bar, one standard error.
3T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
4. depletion either alone or in combination had no significant effect
on the level of protection primed by early eradication of primary
Salmonella infection (Fig. 4A). Since each T cell subset was
found to be depleted !99%, these results cannot be attributed
to inefficient T cell depletion (Fig. 4B). Taken together, these
results demonstrate CD4þ
and CD8þ
T cells are non-essential
direct mediators of protection against recurrent Salmonella
infection.
3.3. Protective Salmonella-specific antibodies are
primed after early infection eradication
Given the sustained protection against recurrent infection
even after CD4þ
and CD8þ
T cell depletion, and the impor-
tance of serum mediated protection especially in mice innately
resistance to Salmonella infection [27], we also enumerated
the impacts of early eradication of primary infection on the
anti-Salmonella serological response. Remarkably, despite
antibiotic treatment beginning day 5, total anti-Salmonella IgG
in these mice was only modestly reduced compared with mice
with persistent infection without antibiotic treatment 45 days
after primary infection (Fig. 5). Anti-Salmonella antibody was
sustained for all IgG isotypes, and for IgG2a and IgG2b, the
response between antibiotic-treated and untreated controls was
nearly indistinguishable (Fig. 5). By contrast to IgG, anti-
Salmonella IgM and IgA were each not sustained because the
background levels in Salmonella infected mice after antibiotic
eradication were significantly reduced compared with mice
without antibiotic treatment and sustained infection. The anti-
Salmonella serological IgG response despite early eradication
of primary infection was specifically triggered by live bacteria
because the same dose of heat-killed Salmonella (104
bacteria)
did not prime a significant increase in antibody titer above the
background levels found in naı¨ve control mice (Fig. 5).
To determine if Salmonella-specific antibody primed after
early antibiotic treatment of primary Salmonella infection
provides protection against recurrent infection, the impact of
adoptively transferred serum on infection susceptibility was
enumerated. After challenge with a sub-lethal inocula of
virulent Salmonella (104
CFU), serum from Salmonella infec-
ted antibiotic-treated mice conferred significant reductions
(!10-fold) in recoverable Salmonella CFUs in the spleen and
liver 5 days post-challenge, while serum from naı¨ve mice did
not significantly impact infection susceptibility (Fig. 6A).
Similarly after challenge with a higher dose of virulent
Salmonella (106
CFU) normally lethal for naı¨ve mice, protec-
tion was partially restored with serum from Salmonella infected
antibiotic-treated mice while serum from naı¨ve control mice
failed to confer protection (Fig. 6B). Together, these results
demonstrate Salmonella-specific antibody is primed despite
early antibiotic-mediated resolution of primary infection, and
that adoptive transfer of serum containing anti-Salmonella
antibody confers protection against recurrent infection.
4. Discussion
Given the widespread use of antimicrobials to eradicate and
reduce the long-term complications associated with human
typhoid, identifying how this therapy impacts protection against
recurrent infection is an important area for investigation.
Although human epidemiological data demonstrating reduced
attack rates of recurrent infection in individuals where primary
Fig. 2. Enrofloxacin eradicates persistent S. typhimurium infection in B6.129F1 mice. Number of recoverable Salmonella CFUs in the spleen and liver at the
indicated time points after infection for mice with (open squares) or without (filled squares) enrofloxacin (2 mg/ml) supplementation in the drinking water
beginning day 5 post-infection. These results are representative of two independent experiments each containing 3-5 mice per group per time point. Dotted line,
limit of detection.
Fig. 3. Protection against secondary challenge with virulent S. typhimurium
despite early eradication of primary infection. Percent survival following
secondary challengewith virulent S. typhimurium (106
CFU) in mice treated with
antibiotics beginning 5 days post-primary infection (104
CFU) (open squares),
mice treated with the same dose of heat-killed Salmonella (filled circles), or naı¨ve
mice given antibiotics in parallel (open circles). The number of mice in each
group is indicated and combined from two to three independent experiments.
4 T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
5. typhoid was treated with antibiotics suggest protective immunity
is generated [8,9], these studies are limited by relatively small
sample sizes, large heterogeneity in immune responses between
individuals, and wide fluctuations in Salmonella inocula during
natural human infection even during outbreak-type settings. To
more definitively address this question, the impact of antibiotic-
mediated clearance of primary Salmonella infection on protec-
tive immunity to recurrent infection was investigated using
a murine model of persistent Salmonella infection where each of
these parameters could be more precisely controlled. We
demonstrate that protection is primed against recurrent Salmo-
nella infection and sustained equally whether antibiotics are
administered during the early (day 5) or later (day 20) phases of
primary Salmonella infection. These results have important
implications for treating and preventing recurrent Salmonella
infection especially in typhoid endemic areas where re-infection
is essentially unavoidable.
Furthermore, using immunological tools and experimental
techniques that are more readily performed in rodent models of
infection, the mediators of protective immunity primed by anti-
biotic-mediated eradication of primary Salmonella infection
were identified. We demonstrate that protection against recurrent
infection is largely mediated by Salmonella-specific antibody
because resistance against secondary infection could be trans-
ferred with serum containing high titers of Salmonella-specific
antibody. These findings are consistent with the demonstration
that antibody plays a dominant role in protection against
secondary infection in mice containing the resistant allele of
Nramp1 that are inherently resistant to Salmonella [27,28], the
protection against human typhoid conferred by the Vi poly-
saccharidevaccine that primes a T cell-independent, Salmonella-
specific serological response [29e33], and the significantly
reduced levels of protection against secondary Salmonella
infection in B cell (antibody)-deficient mice [12,34,35]. Impor-
tantly, since B cells are also potent antigen-presenting cells
required for the optimal priming of Salmonella-specific Th1
CD4þ
cells after infection with live-attenuated strains, the lack of
protection against recurrent infection in B cell-deficient mice
does not discriminate between the antibody-producing and
antigen-presenting roles of these cells [34,36]. To clarify these
different roles, the ability of serum containing Salmonella anti-
body primed by early eradication of primary infection to transfer
protection to naı¨ve mice was demonstrated (Fig. 6). The more
modest level of protection achieved with serum transfer
compared to intact mice primed by primary Salmonella infection
with antibiotic eradiation (Figs. 1, 3 and 6) is most likely due to
diminished anti-Salmonella antibodies related to adoptive
transfer. However, the potential importance of activated macro-
phages primed by live Salmonella that may also contribute to
these differences in protection cannot be excluded [28,37].
Nevertheless taken together, these results illustrate the impor-
tance of sustained Salmonella-specific antibody in protective
immunity against recurrent infection.
In sharp contrast to their role in host defense against primary
infection, neither CD4þ
nor CD8þ
T cells were essential medi-
ators of protective immunity against recurrent infection because
Fig. 4. T cell depletion does not impact protection against secondary Salmonella infection conferred by antibiotic eradication of primary infection. (A) Number of
recoverable Salmonella CFUs in the spleen and liver day 5 post-challenge for mice with CD4þ
and CD8þ
T cells depleted beginning one day prior to secondary
Salmonella challenge (104
CFU). (B) Representative FACS plots demonstrating the efficiency of in vivo CD4þ
and CD8þ
T cell depletions. The numbers in each
plot indicate the percent cells in each gate. These results are combined from two independent experiments containing 7e10 mice per experimental group.
5T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
6. depletion of each cell type individually or in combination did not
increase susceptibility to secondary Salmonella infection in
antibiotic-treated mice [14e16]. Despite these observations, T
cells clearly contribute to and play an important role in host
defense against Salmonella infection because mice with targeted
defects in CD4þ
T cells are highly susceptible to and do not
eradicate even attenuated strains of Salmonella, and similar
defects in host defense against primary Salmonella infection are
Fig. 5. Salmonella-specific IgG is sustained despite early eradication of primary Salmonella infection. Antibody titers of Salmonella-specific IgG, IgM, IgA, IgG1,
IgG2a, IgG2b, and IgG3 in the serum of mice 45 days post-infection (104
CFU) treated with enrofloxacin beginning day 5 (open squares) or without antibiotic
treatment (filled squares), mice treated the same dose of heat-killed Salmonella (filled circles), or naı¨ve mice (open circles). These results represent four inde-
pendent experiments containing 4e6 mice per group.
6 T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
7. found with T cell depletion [13, 16, 21e26]. By extension,
adoptively transferred T cells primed with attenuated Salmonella
together with antibody confers protection in naı¨ve mice, while
T cell ablation eliminates protection against secondary infection
inmice lacking the resistant allele ofNramp1[38]. Thesefindings
in the mouse model of typhoid are consistent with the clinical
observation that recovery from human typhoid and reductions in
typhoid-associated complications such as gastrointestinal
bleeding or perforation each correlates with the development
of cell-mediated immunity [39e41]. Since T cells also play
important and critical roles in the maturation and activation of
antibody-producing cells, the increased susceptibility in T cell-
deficient mice cannot discriminate between whether T cells
provide protection indirectly through enhanced and sustained
help to antibody-producing cells. Our experiments comparing
differences in susceptibility to recurrent infection with T cell
ablation immediately prior to secondary infection demonstrate
that neither CD4þ
nor CD8þ
T cells are essential direct mediators
of protection against recurrent Salmonella infection.
Protection against recurrent infection demonstrated by re-
ductions in recoverable bacterial CFUs and increased survival
despite early antibiotic eradication of primary infection we
demonstrate here is consistent with the delayed time to death for
antibiotic-treated mice after S. typhimurium infection in mice
inherently susceptible to virulent Salmonella [13]. Although the
level of protection primed by antibiotic eradication of primary
infection was sharply reduced compared with that primed by an
attenuatedSalmonella mutant that causesmorepersistentprimary
infection [13], the level of protection we demonstrate using mice
inherently more resistant to virulent Salmonella is sharply
increased (100% survival in 20 mice) even after challenge with
a significantly higher inoculum of virulent Salmonella that is
Fig. 6. Adoptively transferred serum from mice eradicated of primary Salmonella infection confers protection to naı¨ve recipients. (A) Number of recoverable
Salmonella CFUs in the spleen and liver day 5 after infection with virulent S. typhimurium (104
CFU) for mice transferred serum from mice eradicated of primary
Salmonella or no transfer control mice (top). Number of recoverable Salmonella CFUs in the spleen and liver day 5 post-challenge for mice transferred serum from
naı¨ve antibiotic-treated mice or no transfer control mice (bottom). (B) Percent survival after infection with virulent S. typhimurium (106
CFU) in mice transferred
serum from mice eradicated of primary Salmonella (open squares) or control mice without primary infection (filled squares). These results are representative of two
independent experiments containing 8e12 mice per group. Bar, one standard error.
7T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
8. normally lethal even in B6.129F1 mice containing a resistant
allele of Nramp1 (Fig. 3). Taken together, these findings suggest
vaccination strategies that prime a more robust and sustained
serological response compared with primary infection will confer
enhanced protection against Salmonella infection.
Acknowledgements
The authors thank Dr. Stephen McSorley for helpful discus-
sions. This research was supported by National Institutes of
Health grants R01AI087830 (NIAID), the Minnesota Vikings
Children’s Fund, the Minnesota Medical Foundation, and
University of Minnesota Grant-in-Aid.
References
[1] Z.A. Bhutta, I.A. Khan, M. Shadmani, Failure of short-course ceftriaxone
chemotherapy for multidrug-resistant typhoid fever in children: a random-
ized controlled trial in Pakistan, Antimicrobial. Agents Chemother. 44
(2000) 450e452.
[2] E. Gotuzzo, J.G. Morris Jr., L. Benavente, P.K. Wood, O. Levine,
R.E. Black, M.M. Levine, Association between specific plasmids and
relapse in typhoid fever, J. Clin. Microbiol. 25 (1987) 1779e1781.
[3] A. Islam, T. Butler, I. Kabir, N.H. Alam, Treatment of typhoid fever with
ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized
clinical trial, Antimicrobial. Agents Chemother. 37 (1993) 1572e1575.
[4] F.S. Yew, S.K. Chew, K.T. Goh, E.H. Monteiro, Y.S. Lim, Typhoid fever in
Singapore: a review of 370 cases, J. Trop. Med. Hyg. 94 (1991) 352e357.
[5] A. Islam, T. Butler, L.R. Ward, Reinfection with a different Vi-phage
type of Salmonella typhi in an endemic area, The Journal of Infectious
Diseases 155 (1987) 155e156.
[6] J. Wain, T.T. Hien, P. Connerton, T. Ali, C.M. Parry, N.T. Chinh, H. Vinh,
C.X. Phuong, V.A. Ho, T.S. Diep, J.J. Farrar, N.J. White, G. Dougan,
Molecular typing of multiple-antibiotic-resistant Salmonella enterica
serovar Typhi from Vietnam: application to acute and relapse cases of
typhoid fever, J. Clin. Microbiol. 37 (1999) 2466e2472.
[7] C.M. Parry, T.T. Hien, G. Dougan, N.J. White, J.J. Farrar, Typhoid fever,
N. Engl. J. Med. 347 (2002) 1770e1782.
[8] H.L. Dupont, R.B. Hornick, M.J. Snyder, A.T. Dawkins, G.G. Heiner,
T.E. Woodward, Studies of immunity in typhoid fever. Protection
induced by killed oral antigens or by primary infection, Bull. World
Health Organ. 44 (1971) 667e672.
[9] D.E. Marmion, G.R. Naylor, I.O. Stewart, Second attacks of typhoid
fever, J. Hyg. (Lond). 51 (1953) 260e267.
[10] S. Gaines, J.G. Tully, W.D. Tigertt, Studies on infection and immunity in
experimental typhoid fever. II. Susceptibility of recovered animals to re-
exposure, J. Exp. Med. 112 (1960) 1023e1036.
[11] S.K. Hoiseth, B.A. Stocker, Aromatic-dependent Salmonella typhimu-
rium are non-virulent and effective as live vaccines, Nature 291 (1981)
238e239.
[12] S.J. McSorley, M.K. Jenkins, Antibody is required for protection against
virulent but not attenuated Salmonella enterica serovar typhimurium,
Infect. Immun. 68 (2000) 3344e3348.
[13] A. Griffin, D. Baraho-Hassan, S.J. McSorley, Successful treatment of
bacterial infection hinders development of acquired immunity, J. Immunol.
183 (2009) 1263e1270.
[14] R.A. Luu, K. Gurnani, R. Dudani, R. Kammara, H. van Faassen,
J.C. Sirard, L. Krishnan, S. Sad, Delayed expansion and contraction of
CD8þ T cell response during infection with virulent Salmonella typhi-
murium, J. Immunol. 177 (2006) 1516e1525.
[15] H.W. Mittrucker, A. Kohler, S.H. Kaufmann, Characterization of the
murine T-lymphocyte response to Salmonella enterica serovar Typhi-
murium infection, Infect. Immun. 70 (2002) 199e203.
[16] T.M. Johanns, J.M. Ertelt, J.H. Rowe, S.S. Way, Regulatory T cell
suppressive potency dictates the balance between bacterial proliferation
and clearance during persistent Salmonella infection, PLoS Pathogens 6
(2010).
[17] S.J. McSorley, S. Asch, M. Costalonga, R.L. Reinhardt, M.K. Jenkins,
Tracking salmonella-specific CD4 T cells in vivo reveals a local mucosal
response to a disseminated infection, Immunity 16 (2002) 365e377.
[18] T.M. Johanns, J.M. Ertelt, J.C. Lai, J.H. Rowe, R.A. Avant, S.S. Way,
Naturally occurring altered peptide ligands control Salmonella-specific
CD4þ T cell proliferation, IFN-gamma production, and protective
potency, J. Immunol. 184 (2010) 869e876.
[19] A. Srinivasan, M. Nanton, A. Griffin, S.J. McSorley, Culling of activated
CD4 T cells during typhoid is driven by Salmonella virulence genes,
J. Immunol. 182 (2009) 7838e7845.
[20] A.F. Cunningham, F. Gaspal, K. Serre, E. Mohr, I.R. Henderson,
A. Scott-Tucker, S.M. Kenny, M. Khan, K.M. Toellner, P.J. Lane, I.C.
MacLennan, Salmonella induces a switched antibody response without
germinal centers that impedes the extracellular spread of infection,
J. Immunol. 178 (2007) 6200e6207.
[21] L. Guilloteau, D. Buzoni-Gatel, F. Bernard, I. Lantier, F. Lantier, Salmo-
nella abortusovis infection in susceptible BALB/cby mice: importance of
Lyt-2þ and L3T4þ T cells in acquired immunity and granuloma forma-
tion, Microb. Pathog. 14 (1993) 45e55.
[22] J. Hess, C. Ladel, D. Miko, S.H. Kaufmann, Salmonella typhimurium
aroAÀ infection in gene-targeted immunodeficient mice: major role of
CD4þ TCR-alpha beta cells and IFN-gamma in bacterial clearance
independent of intracellular location, J. Immunol. 156 (1996) 3321e3326.
[23] W.F. Lo, H. Ong, E.S. Metcalf, M.J. Soloski, T cell responses to Gram-
negative intracellular bacterial pathogens: a role for CD8þ T cells in
immunity to Salmonella infection and the involvement of MHC class Ib
molecules, J. Immunol. 162 (1999) 5398e5406.
[24] C. Nauciel, Role of CD4þ T cells and T-independent mechanisms in
acquired resistance to Salmonella typhimurium infection, J. Immunol.
145 (1990) 1265e1269.
[25] K. Sinha, P. Mastroeni, J. Harrison, R.D. de Hormaeche, C.E. Hormaeche,
Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause
progressive infections in athymic (nu/nu) BALB/c mice, Infect. Immun. 65
(1997) 1566e1569.
[26] B.C. Weintraub, L. Eckmann, S. Okamoto, M. Hense, S.M. Hedrick,
J. Fierer, Role of alphabeta and gammadelta T cells in the host response
to Salmonella infection as demonstrated in T-cell-receptor-deficient mice
of defined Ity genotypes, Infect. Immun. 65 (1997) 2306e2312.
[27] T.K. Eisenstein, L.M. Killar, B.M. Sultzer, Immunity to infection with
Salmonella typhimurium: mouse-strain differences in vaccine- and serum-
mediated protection, The Journal of Infectious Diseases 150 (1984)
425e435.
[28] F.M. Collins, Vaccines and cell-mediated immunity, Bacteriol. Rev. 38
(1974) 371e402.
[29] I.L. Acharya, C.U. Lowe, R. Thapa, V.L. Gurubacharya, M.B. Shrestha,
M. Cadoz, D. Schulz, J. Armand, D.A. Bryla, B. Trollfors, et al., Prevention
of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmo-
nella typhi. A preliminary report, N. Engl. J. Med. 317 (1987) 1101e1104.
[30] A. Fraser, M. Paul, E. Goldberg, C.J. Acosta, L. Leibovici, Typhoid fever
vaccines: systematic review and meta-analysis of randomised controlled
trials, Vaccine 25 (2007) 7848e7857.
[31] K.P. Klugman, I.T. Gilbertson, H.J. Koornhof, J.B. Robbins, R. Schneerson,
D. Schulz, M. Cadoz, J. Armand, Protective activity of Vi capsular poly-
saccharide vaccine against typhoid fever, Lancet 2 (1987) 1165e1169.
[32] M.M. Levine, C.O. Tacket, M.B. Sztein, Host-Salmonella interaction:
human trials, Microbes Infect. 3 (2001) 1271e1279.
[33] H.H. Yang, C.G. Wu, G.Z. Xie, Q.W. Gu, B.R. Wang, L.Y. Wang,
H.F. Wang, Z.S. Ding, Y. Yang, W.S. Tan, W.Y. Wang, X.C. Wang, M. Qin,
J.H. Wang, H.A. Tang, X.M. Jiang, Y.H. Li, M.L. Wang, S.L. Zhang, G.L.
Li, Efficacy trial of Vi polysaccharide vaccine against typhoid fever in
south-western China, Bull. World Health Organ. 79 (2001) 625e631.
[34] P. Mastroeni, C. Simmons, R. Fowler, C.E. Hormaeche, G. Dougan, Igh-
6(À/À) (B-cell-deficient) mice fail to mount solid acquired resistance to
oral challenge with virulent Salmonella enterica serovar typhimurium
and show impaired Th1 T-cell responses to Salmonella antigens, Infect.
Immun. 68 (2000) 46e53.
8 T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004
9. [35] H.W. Mittrucker, B. Raupach, A. Kohler, S.H. Kaufmann, Cutting edge:
role of B lymphocytes in protective immunity against Salmonella typhi-
murium infection, J. Immunol. 164 (2000) 1648e1652.
[36] S. Ugrinovic, N. Menager, N. Goh, P. Mastroeni, Characterization and
development of T-Cell immune responses in B-cell-deficient (Igh-6(À/À))
mice with Salmonella enterica serovar Typhimurium infection, Infect.
Immun. 71 (2003) 6808e6819.
[37] L.M.Killar, T.K. Eisenstein,Immunity toSalmonellatyphimuriuminfection
in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent
live S. typhimurium strain as a vaccine, Infect. Immun. 47 (1985) 605e612.
[38] P. Mastroeni, B. Villarreal-Ramos, C.E. Hormaeche, Adoptive transfer of
immunity to oral challengewith virulent salmonellae in innately susceptible
BALB/c mice requires both immune serum and T cells, Infect. Immun. 61
(1993) 3981e3984.
[39] P. Rajagopalan, R. Kumar, A.N. Malaviya, A study of humoral and cell-
mediated immune response following typhoid vaccination in human
volunteers, Clin. Exp. Immunol. 47 (1982) 275e282.
[40] P. Rajagopalan, R. Kumar, A.N. Malaviya, Immunological studies in
typhoid fever. II. Cell-mediated immune responses and lymphocyte
subpopulations in patients with typhoid fever, Clin. Exp. Immunol. 47
(1982) 269e274.
[41] V.N. Sarma, A.N. Malaviya, R. Kumar, O.P. Ghai, M.M. Bakhtary,
Development of immune response during typhoid fever in man, Clin. Exp.
Immunol. 28 (1977) 35e39.
9T.M. Johanns et al. / Microbes and Infection xx (2010) 1e9
Please cite this article in press as: T.M. Johanns et al., Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to
recurrent infection, Microbes and Infection (2010), doi:10.1016/j.micinf.2010.11.004