Control Of Infectious Diseases PDF

Control of Infectious Disease Learning Goals 1. Describe the mechanisms of action associated with drugs that inhibit cell wall biosynthesis, protein synthesis, membrane function, nucleic acid synthesis, and metabolic pathways 2. Explain the differences between modes of action of drugs t...

Control of Infectious Disease Learning Goals 1. Describe the mechanisms of action associated with drugs that inhibit cell wall biosynthesis, protein synthesis, membrane function, nucleic acid synthesis, and metabolic pathways 2. Explain the differences between modes of action of drugs that target fungi, protozoa, helminths, and viruses 3. Explain the concept of drug resistance 4. Describe how microorganisms develop or acquire drug resistance 5. Describe the different mechanisms of antimicrobial drug resistance 6. Describe the history and mechanisms of vaccines in protecting against infectious disease. 7. Describe the four different types of immunity with several specific examples for each 8. Contrast the different types of vaccines including killed, live-attenuated, recombinant DNA, and mRNA vaccines. 9. Discuss other mechanisms to enhance immune responses (eg., Gene therapy, monoclonal antibodies) Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 2 Introduction: Human control of disease has made incredible progress in the last century. o Due to vaccines, antimicrobial drugs, and improvements in sanitation and hygiene. o premature death from infectious disease has dropped considerably. We will examine these methods and new challenges that could reverse the improvements. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 3 Historical Aspects of Infectious Disease Treatment and Control: (1 of 3) How did we deal with infectious disease in the past? Human diseases usually require large populations of susceptible hosts. They also require the hosts to stay put long enough to contaminate their water and attract animal vectors (rats, fleas, etc.). As populations rose in number, and humans moved toward agriculture (away from hunting and gathering), diseases became more prevalent. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 4 Historical Aspects of Infectious Disease Treatment and Control: (2 of 3) Lack of scientific understanding led to religion and superstition “explaining” diseases. o Sickness was a punishment from supernatural beings for immorality or sinfulness. o Afflicted individuals were often cast out of society. The ancient Greeks were the first to separate religious superstitions from disease. o Hippocrates (circa 400 BC) lectured that disease was a result of physiological imbalance. o He promoted the idea of restoring balance through diet. o Others took his ideas to extremes, using bloodletting or leeches to try to remove “excess” blood to “restore balance.” Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 5 Historical Aspects of Infectious Disease Treatment and Control: (3 of 3) Many ancient practices continued until the mid-1800s, when Koch, Pasteur, and Lister provided evidence for the germ theory of disease. Despite these problems, two methods of disease control have been used for centuries with modest success. o Quarantine o Vaccination (sporadically) We will discuss these methods later. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 6 Antimicrobial Drugs: (1 of 27) What kinds of drugs are used to treat infections, and how do they work? Antimicrobial drugs are different from antiseptics and disinfectants. o They are often administered internally. o They exhibit selective toxicity (more toxic to an infectious microbe than to the host/host cells). o They may be of natural origin or chemically synthesized. o They may be highly effective at eliminating one class of microbes (e.g., bacteria) while ineffective at eliminating others. o Their history of use extends across the past century. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 7  Antimicrobial Drugs: (2 of 27) Antibiotics are the most important, historically. o Alexander Fleming in 1928 Observations of bread mold Penicillium inhibiting S. aureus cultures o Led to a surge in research on naturally occurring antibiotic compounds o Analysis of molecular structure Led to classification Further research on devising synthetic equivalents Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 8 Antimicrobial Drugs: (4 of 27) 1 Antibiotics and their origins Source Natural antibiotic Semisynthetic derivatives Antibacterial antibiotics Pénicillium chryosgenum (fungi) Penicillin G, penicillin V Methicillin, ampicillin, amoxicillin, carbenicillin, oxacillin Cephalosporium species (fungi) Cephalosporin Cephalexin, cephradine, cefradoxil, ceftazidime a Streptomyces griseus Streptomycin NA Streptomyces aureofaciens Tetracycline Doxycycline, oxytetracycline a Streptomyces venezuelae Chloramphenicol NA Streptomyces erythreus Erythromycin Azithromycin, clarithromycin Streptomyces kanamyceticus Kanamycin Amikacin, arbekacin a Streptomyces tenebrarius Tobramycin NA a Streptomyces fradiae Neomycin NA Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 9 Antimicrobial Drugs: (5 of 27) 1 Antibiotics and their origins Source Natural antibiotic Semisynthetic derivatives Streptomyces mediterranei Rifamycin Rifampin Amycolatopsis orientalis Vancomycin Ramoplanin a Micromonospora species Gentamicin NA a Bacillus licheniformis Bacitracin NA a Bacillus polymyxa Polymyxins NA Antifungal antibiotics a Penicillium griseofulvum Griseofulvin NA a Streptomyces nodosus Polyenes NA a NA: not applicable; not developed or not commonly used. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 10 Antimicrobial Drugs: (6 of 27) Antibiotics often interfere with o Peptidoglycan synthesis o Membrane integrity o DNA synthesis o Transcription o Folic acid synthesis o Ribosome function Structure often determines what can be affected. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 11 Antimicrobial Drugs: (7 of 27) Structure plays an important role in antibiotic effectiveness. o Structure of the drug molecule is critical. o Structure of the microbe itself is also important. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 12 Antimicrobial Drugs: (8 of 27) 2 Action, structure, and targets of antibacterial drug groups Action Class/group Structure Target Examples Antibacterial drugs Natural and semisynthetic antibiotics Inhibition of -lactams Peptidoglycan Penicillins G and V, peptidoglycan transpeptidases methicillin, cephalosporins, synthesis The chemical structure of penicillin G shows a ring attached to a C H 2 group, (PBPs) monobactams, carbenicillin with a C O N H and ring group with a sulfur on the other side. Glycopeptides Peptidoglycan Vancomycin, peptide avoparcin subunits Vancomycin's chemical structure is a large group of ring groups with many O H, N H 2, and C H 3 side chains. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 13 Antimicrobial Drugs: (9 of 27) Action Class/group Structure Target Examples Inhibition of Bacitracin Bacitracin's chemical structure has a Isoprenyl Bacitracin carbon chain at the top with various peptidoglycan (topical use) side groups. It is attached to different pyrophosphate synthesis amino acid side chains, including Leu, glu, I l e, asp, and lys. Disruption of Polymyxin B Polymyxin B has a straight portion of Membranes Polymyxin B, polymyxin E a carbon chain attached to a large membranes (topical use) circular portion with side chain groups hanging off of it. Inhibition of Aminoglyco- Gentamicin has 3 rings attached to 16S rRNA of 30S Gentamicin, neomycin, each other, with O H and N H 2 ribosome sides groups on the rings. ribosome streptomycin, tobramycin function subunit Source: Black, Microbiology: Principles and Explorations, copyright 2012, John Wiley & Sons, Inc. This material is reproduced with permission of John Wiley & Sons, Inc. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 14 Antimicrobial Drugs: (10 of 27) Action Class/group Structure Target Examples Inhibition of Macrolides Peptidyl Erythromycin, spectinomycin, ribosome transferase carbomycin function site of 50S ribosome subunit Erythromycin has a star shaped group attached to 2 smaller rings. Tetracyclines 30S ribosome Tetracycline, doxycycline, subunit oxytetracycline Tetracycline has 4 rings in a row with O, O H, and C H 3 groups. Chloramphenicol 23S rRNA of 50S Chloramphenicol ribosome subunit Chloramphenicol has a ring attached to a carbon chain with H, O, and C H 2 side groups. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 15 Antimicrobial Drugs: (11 of 27) Action Class/group Structure Target Examples Inhibition of Rifamycins -subunit of Rifampin, rifabutin, transcription bacterial RNA rifapentine Polymerase Rifampin has 2 rings and a large, bent carbon chain around it. One of the rings is attached to a carbon chain with an N based ring. Synthetic antibiotics Ciprofloxacin has 3 rings with some carbon side chains and an F group. One Inhibition of Quinolones of the rings is N based. Gram-negative Nalidixic acid, nucleic DNA gyrase or oxolinic acid, acid synthesis Gram-positive fluoroquinolones topoisomerase IV (e.g., ciprofloxacin) Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 16 Antimicrobial Drugs: (12 of 27) Action Class/group Structure Target Examples Inhibition of Sulfonamides Dihydropteroate Sulfisoxazole, sulfanilamide nucleic synthetase acid synthesis (folic acid pathway) Sulfanilamide has a central ring with an N H 2 group on top and an S O 2 N H 2 group on the bottom. Inhibition of Trimethoprim Dihydrofolate Trimethoprim nucleic reductase (folic acid synthesis acid pathway) Trimethoprim has 2 rings attached by a carbon the center. One has N H 2 groups and the other has O C H 3 groups. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 17 Antimicrobial Drugs: (13 of 27) Antibacterial drugs o Bacteriocidal = Directly kill the microbes treated o Bacteriostatic = Prevent replication of bacteria but do not kill them o Selected classes for further examination Inhibitors of peptidoglycan synthesis Inhibitors of ribosome function Inhibitors of nucleic acid synthesis Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 18 Antimicrobial Drugs: (17 of 27) Antifungal drugs o Much more problematic (eukaryotes!) o Very few available drugs , and the few must focus on Disruption of cell ergosterol (instead of cholesterol in human cell membranes) Inhibition of chitin cell wall structures Selective inhibition of fungal mitosis (difficult!) Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 19 Antimicrobial Drugs: (18 of 27) 3 Action, structure, and targets of antifungal drug groups Action Class/group Structure Target Examples Antibacterial drugs Natural and semisynthetic antibiotics Griseofulvin has 2 rings with several O C H 3 side groups and a C l group on Inhibition of Griseofulvin one of the rings. Tubulin Griseofulvin mitosis Inhibition of Echinocandins β-1, 3-D-glucan Caspofungin, cell wall synthase papulacandin synthesis Caspofungin is a large molecule with a long carbon chain at the bottom and a complex network of carbon chains and rings at the top. There are several O, O H, and N H groups on the upper portion of the molecule. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 20 Antimicrobial Drugs: (19 of 27) Action Class/group Structure Target Examples Disruption of Polyenes Plasma Amphotericin B, plasma membrane membrane nystatin Amphotericin B is comprised of a long, horizontal loop of carbon chains with a ergosterol ring group on the right. There are several O and O H side groups on the horizontal loop, and O H, N H 2, and C H 3 groups on the ring. Synthetic antibiotics Azoles C14- Fluconazole, demethylase ketoconazole, clotrimazole, miconazole Fuconazole has 3 rings. The central ring has 2 F side groups. A short carbon chain connects the top of the central ring with either of the side rings. Both side rings have 3 N's in them and 2 double bonds. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 21 Antimicrobial Drugs: (20 of 27) Antiprotozoal drugs (eukaryotes again!) o Varied life cycle forms also complicates things. o Basic drug methods include (but are not limited to): Inhibition of heme detoxification inside malaria parasites as they feed on hemoglobin (chloroquine) Free radical formation in presence of ferrous iron effective against malaria parasites in erythrocytic stage (artemisinin) Destruction of DNA by incorporation of drugs into new DNA that causes breakage of the strands (metronidazole) Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 22 Antimicrobial Drugs: (21 of 27) Antiprotozoal drugs 4 Action, structure, and targets of antiprotozoal drug groups Action Class/group Structure Target Examples Antiprotozoal drugs Inhibition of Quinolines Hemozoin Quinine, chloroquine, heme (see Section primaquine, mefloquine detoxification 23.2) Chloroquine has 2 rings connected to each other. There is a C l group on the left ring, and a large N and C side group on the right ring. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 23 Antimicrobial Drugs: (22 of 27) Action Class/group Structure Target Examples Free radical Artemisinin Malarial Artemisinin, artemether, formation calciumdepen artesunate dent ATPase Artemisinin has 3 rings connected together at a central point. There are several O, H and C H 3 groups on the rings. Metronidazole has a ring composed of C and N with a C H 3 group, and N O Destruction of Metronidaz 2 group, and a C H 2 C H 2 O H group. DNA Metronidazole DNA ole Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 24 Antimicrobial Drugs: (23 of 27) Antiviral drugs o Tricky because viruses often use host cell processes If you inhibit a host cell process, toxicity will be high. o Common mechanisms involve Inhibition of nucleic acid synthesis o Often through nucleoside/nucleotide analogues (AZT, acyclovir) o Inhibition of virus life-cycle steps (intracellular uncoating of flu virus) o AZT somehow specific to HIV, because it targets the reverse transcriptase Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 25 Antimicrobial Drugs: (24 of 27) 5 Action, structure, and targets of antiviral drug groups Action Class/group Structure Target and Use Examples Antiviral drugs Interference Nucleoside DNA and/or Acyclovir, AZT, with nucleic acid Analogs RNA ribavirin, tenofovir, synthesis HIV, herpes vidarabine, idoxuridine viruses, hepatitis C Acyclovir, a guanine analog, has 2 rings containing N and C. One has N, O, N H, and N H 2 groups, and the other has a long carbon and oxygen chain on the bottom. virus Inhibition of Adaman- M2 Protein Amantadine, virus uncoating itane (an ion rimantadine channel needed for release of nucleocapsids) Influenza A virus Amantadine has a complex ring with a N H 2 H C l group on top. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 26 Antimicrobial Drugs: (25 of 27) Action Class/group Structure Target and Use Examples Inhibition of Neuramini- Neuraminidase Oseltamivir Virus release dase (needed to (Tamiflu), zanamivir inhibitor cleave terminal (Relenza) sialic acid to which virus is tethered upon exit from cell) Oseltamivir has a central ring with an O O C H 3 group, a carbon and oxygen chain group, and a N, O, and C H 3 group, as well as an N H 2 group. Influenza virus Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 27 Antimicrobial Drugs: (26 of 27) Action Class/group Structure Target and Use Examples Antiviral drugs Inhibition of NS5A Protein 5A Daclatasvir viral replication inhibitor (needed for RNA genome replication and assembly of virions) Hepatitis C og, has 2 rings containing N and C. One has N, O, N H, and N H 2 groups, and the other has a long carbon and oxygen chain on the bottom. virus Inhibition of Protease HIV protease Amprenavir, viral assembly inhibitor (drugs ending fosamprenavir, in –navir) and boceprevir, simeprevir hepatis C virus (drugs ending in –previr) Amantadine has a complex ring with a N H 2 H C l group on top. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 28 Antimicrobial Drugs: (27 of 27) Target and Action Class/group Structure Use Examples Antiviral drugs Inhibition of Pegylated Host and viral Peg- viral translation interferon RNA needed interferon (Synthetic for Type I translation, interferons) activates p53 pathway for cell apoptosis and infected and neighboring cells Hepatitis B and C viruses, herpes viruses Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 29 Antimicrobial Drug Resistance: (1 of 17) How do microbes become drug-resistant? Adaptation to selective pressures drives genetic change in microbes. Drug resistance genetic changes are negative. o The CDC estimates 2 million people contract bacterial infections in hospitals yearly. o Of these, approximately 23,000 die. o About 70% of the bacterial pathogens causing these infections show resistance to at least one antibacterial drug. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 30 Antimicrobial Drug Resistance: (2 of 17) So what is the evidence for selection for resistance in clinical settings? o Changes in antimicrobial drug use are positively correlated with changes in prevalence of resistance. o Increasing antibiotic treatment lengths increases resistant- microbe colonization rates. o The more antimicrobial drug use in a facility, the more drug resistance that can be found. o Patients with resistant strains receive antibiotics more often Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 31 Antimicrobial Drug Resistance: (10 of 17) Natural selection and drug resistance o Susceptibility testing methods Kirby-Bauer disk diffusion test Epsilometer test (Etest) Dilution susceptibility tests Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 32 Antimicrobial Drug Resistance: (11 of 17) Zone of inhibition diameter and susceptibility for Staphylococcus aureus Zone of growth inhibition diameter (mm) Quantity in Resis Interme Suscep Antimicrobial drug disk (μ g) tant diate tible Ampicillin 10 13 Chloramphenicol 30 17 Erythromycin 15 17 Tetracycline 30 18 Streptomycin 10 14 Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 33 Antimicrobial Drug Resistance: (17 of 17) Combating drug resistance o So what do we do about this problem? Reduce use. Use selective drugs. Use multidrug cocktails. Use effective infection control. Develop new vaccines and improve access. Develop alternatives/develop drugs in a smarter way. People with primary immunodeficiencies, as well as others who are immunocompromised, rely on the prophylactic use of antimicrobials to prevent infection. Not only may these drugs become less effective as preventative measures, but there is already evidence that resulting infections are harder to treat. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 34 Immunization and Vaccines: (1 of 26) What are vaccines, and how are they used to control infectious disease? History of vaccination o Smallpox is a historic illness plaguing humankind. It is viral in nature, and easily transmitted via aerosols. The mortality rate is very high, ranging up to 50 to 90%. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 35 Immunization and Vaccines: (2 of 26) o Previous control attempts had been made but weren’t very safe or as effective as necessary. o Edward Jenner coined the term vaccination in 1798 with his work protecting people from smallpox. Jenner observed that milkmaids had smallpox less frequently than the rest of the population but they would get another lesser disease (cowpox). He purposely infected a boy with cowpox, then later with smallpox—and the boy didn’t develop the disease. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 36 FIGURE 18.26 (a) A painting of Edward Jenner depicts a cow and a milkmaid in the background. (b) Lesions on a patient infected with cowpox, a zoonotic disease caused by a virus closely related to the one that causes smallpox. (credit b: modification of work by the Centers for Disease Control and Prevention) Immunization and Vaccines: (3 of 26) History of vaccination o Fast-forward 150 years, and technology had improved enough for a concerted global vaccination effort. This effort was successful, eliminating smallpox in the wild. o Not without risk—the vaccine is associated with some risks for serious side effects. Government research labs maintain the last known quantities of the wild virus for research purposes. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 38 Immunization and Vaccines: (4 of 26) Vaccine design o Vaccines confer protection by initiating immune memory. Specialized T and B cells that are produced post-stimulation o The ideal vaccine generates a high level of immune memory without serious side effects. o Different types of vaccines include Attenuated Inactivated Subunit Nucleic acid Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 39 FIGURE 18.2 This graph illustrates the primary and secondary immune responses related to antibody production after an initial and secondary exposure to an antigen. Notice that the secondary response is faster and provides a much higher concentration of antibody. FIGURE 18.23 Compared to the primary response, the secondary antibody response occurs more quickly and produces antibody levels that are higher and more sustained. The secondary response mostly involves IgG. FIGURE 18.24 The four classifications of immunity. (credit top left photo: modification of work by USDA; credit top right photo: modification of work by “Michaelberry”/Wikimedia; credit bottom left photo: modification of work by Centers for Disease Control and Prevention; credit bottom right photo: modification of work by Friskila Silitonga, Indonesia, Centers for Disease Control and Prevention) Immunization and Vaccines: (5 of 26) Vaccine design: Attenuated vaccines o Composed of living (but weakened) pathogen. o Tend to produce high immunity because the microbe replicates in the body. This exposes the immune system to a higher level of foreign antigen over a greater period of time. An added benefit is the individual might shed vaccine microbe to other individuals, indirectly vaccinating them. o There is a possibility that the weakened pathogen could revert to a more pathogenic state, however. o One of the polio vaccines is a prime example of this and will be discussed shortly. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 43 Immunization and Vaccines: (6 of 26) Vaccine design: Inactivated vaccines o Consist of whole virus/cells that have been inactivated by heat or chemicals. Benefits include that the microbe can’t revert, can’t replicate, and can’t spread. Drawbacks include lower/shorter stimulation of immune responses, a need for multiple injections, and greater risk of negative side effects. o An example of an older vaccine (no longer in use) was killed whole- cell pertussis vaccine. Crude prep of microbial components. Induced convulsions in 0.1% of infants (with a smaller percentage suffering brain damage). Newer vaccine is a safer acellular subunit prep. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 44 Immunization and Vaccines: (7 of 26) Vaccine design: Subunit vaccines/acellular vaccines o Consist of 1+ isolated protective antigens (no whole cells or viruses) Defined composition is safer. May require several injections to produce strong immunity. The current DTaP (or Tdap) vaccine (diphtheria, tetanus, and pertussis) is an example of this type. o Conjugate vaccines are a modified form of this method. They link a polysaccharide antigen to an immunogenic protein. The idea is that the polysaccharide is a poor antigen on its own. When you link it to a strong stimulating protein, you can get better responses overall. The Hib vaccine, protecting against H. influenzae type b bacteria that cause meningitis, is an example. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 45 Immunization and Vaccines: (8 of 26) When do we get vaccines, and which ones? Vaccines recommended by the Centers for Disease Control and Prevention for bacterial and viral diseases Vaccine Disease/pathogen target Description Vaccines against bacterial diseases Hib Haemophilus influenzae type b Conjugated polysaccharide (polyribitol causing meningitis phosphate) subunit vaccine DTaP Against diphtheria Combination subunit vaccine for children (Corynebacterium containing inactivated diphtheria, tetanus, and diphtheriae), tetanus pertussis toxins. Includes other selected antigens (Clostridium tetani), and of B. pertussis to reduce colonization pertussis (Bordetella pertussis) Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 46 Immunization and Vaccines: (9 of 26) Vaccine Disease/pathogen target Description Tdap Against diphtheria, tetanus, and Combination subunit vaccine for adolescents pertussis containing inactivated tetanus and diphtheria toxins. Contains reduced concentrations of inactivated diphtheria and pertussis components Td Against diphtheria and tetanus Combination subunit vaccine for adults containing inactivated tetanus and diphtheria toxins PCV13 Streptococcus pneumoniae Conjugated polysaccharide subunit vaccine causing pneumococcal meningitis containing the 13 most common capsule in children polysaccharides associated with meningitis in children PPSV23 Streptococcus pneumoniae Non‐conjugated polysaccharide subunit vaccine causing pneumococcal meningitis containing the 23 most common types of capsule and invasive disease in adults polysaccharides associated with adult disease Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 47 Immunization and Vaccines: (10 of 26) Vaccine Disease/pathogen target Description MCV4 Neisseria meningitidis causing Conjugated polysaccharide subunit vaccine meningitis in young adults containing the four most common types of capsule polysaccharides Vaccines against viral diseases RV Rotovirus causing gastroenteritis Attenuated oral vaccine containing several strains in children of type A rotovirus IPV Poliovirus causing poliomyelitis Killed vaccine containing poliovirus types 1, 2, and 3 Influenza Influenza virus causing seasonal Polyvalent vaccine containing the dominant influenza circulating strains of influenza A and B types HepB Hepatitis B virus causing liver Recombinant subunit vaccine containing the disease envelope protein HBsAg produced in yeast Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 48 Immunization and Vaccines: (11 of 26) Vaccine Disease/pathogen target Description MMR Measles, mumps, and rubella Killed combination vaccine viruses Varicella Herpes varicella‐zoster virus Live, attenuated vaccine for protection against causing chickenpox primary infection Zoster Herpes varicella‐zoster virus Live, attenuated vaccine for protection against causing shingles reactivation in adults HepA Hepatitis A virus causing liver Killed vaccine disease HPV Human papillomavirus causing Recombinant subunit vaccine containing capsid cervical, anal, penile, and proteins of strains associated with the majority oropharyngeal cancer of papillomavirus‐induced cancers. The vaccine Gardasil 9a contains capsids from an additional two of the most common strains causing genital warts (11 and 6). a Gardasil 9 Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 49 Immunization and Vaccines: (12 of 26) When do we get vaccines, and which ones? Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 50 Immunization and Vaccines: (13 of 26) Vaccine design: DNA/RNA vaccines o Consist of a cloned gene(s) in a DNA vector. Delivered to cells by injection, engineered virus, or electroporation o If the gene is picked up and expressed, it stimulates a protective immune response. Similar to recombinant subunit vaccines Benefit is longer exposure (stronger response). Vaccines don’t contain live microbes, avoiding the dangers associated with attenuated vaccines. o Largely still experimental. Covid – 19 Pfizer and moderna are mRNA/Asta and JJ are DNA Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 51 Immunization and Vaccines: (14 of 26) Vaccine efficiency o No vaccine is 100% effective, but efficacy has been studied extensively. Childhood vaccine effectiveness rates are usually 85–90%. Estimating infected individuals in a population becomes a numbers game. Opponents of vaccination use these numbers to argue that vaccines do not work—which is a misrepresentation. Imagine if no one was vaccinated, instead… Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 52 Immunization and Vaccines: (15 of 26) Herd immunity o In reality, you can never immunize 100% of a population... but you don’t have to. o If you can effectively reduce the number of susceptible individuals, an illness can’t progress in a population effectively. A. Unvaccinated population B. Vaccinated population Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 53 Immunization and Vaccines: (16 of 26) Herd immunity o Herd immunity threshold = % of population that needs to have immunity to prevent spread of a disease This value can depend on The susceptibility of the population How communicable the disease agent is Population density Vaccine efficiency If herd immunity is high enough, global eradication of a disease is possible. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 54 Immunization and Vaccines: (18 of 26) Polio: A near success o Poliovirus is transmitted via the fecal–oral route. In most cases, a mild gastrointestinal illness results. In a smaller percentage of cases, the virus “takes a wrong turn” and enters the central nervous system. This can result in varied degrees of paralysis. A. Rows of polio patients in iron lung machines B. Girl receiving breathing assistance Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 55 Immunization and Vaccines: (19 of 26) Polio: Changing patterns of infection o In endemic areas with poor sanitation and water quality, incidence of paralytic polio is low. Most individuals are infected very early in life, and chances of the “wrong turn” event are lower. o In endemic areas with improved sanitation and water quality, exposure to poliovirus occurs later in life. Chances for paralytic polio increase with age. o This is genuinely a case where improvements in sanitation and water quality may have exacerbated the issue of paralytic polio. We can’t go back to poor sanitation—so vaccinate! Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 56 Immunization and Vaccines: (21 of 26) Polio vaccines: Inactivated versus attenuated o Inactivated polio vaccine (IPV, “Salk” vaccine) began being used in 1955. o Oral polio vaccine (OPV, “Sabin” vaccine) began being used in the 1960s. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 57 Immunization and Vaccines: (22 of 26) 7 Comparison of inactivated and attenuated oral polio vaccines Inactivated polio vaccine (IPV) Attenuated, oral polio vaccine (OPV) Developed by Jonas Salk Developed by Albert Sabin Injected Oral Expensivea (needles, trained Inexpensivea (no needles, no medical personnel, 3–4 boosters) special training, 2 boosters) Serum immunity only (IgG) Mucosal (IgA) and serum immunity (IgG) Prevents poliomyelitis but not infection Prevents poliomyelitis and infection with wild virus from wild virus (carrier) (cannot transmit wild virus) Does not eliminate wild virus Eliminates wild virus No risk of vaccine‐associated poliomyelitis Risk of vaccine‐associated poliomyelitis No transmission of vaccine strains Transmission of vaccine strains aBoth formulations require refrigeration. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 58 Immunization and Vaccines: (23 of 26) Polio vaccine issues o OPV is “better” at stimulating immunity, but It can revert and cause illness. It requires more careful handling and refrigeration. o IPV is “worse” at stimulating immunity, but It can’t revert. o For global eradication of polio, all immunization will eventually have to shift back to IPV instead of OPV. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 59 FIGURE 18.1 Polio was once a common disease with potentially serious consequences, including paralysis. Vaccination has all but eliminated the disease from most countries around the world. An iron-lung ward, such as the one shown in this 1953 photograph, housed patients paralyzed from polio and unable to breathe for themselves. Conclusion: This chapter has examined how we can treat and prevent pathogenic infections. While no method is 100% effective, understanding how the methods work and their benefits/drawbacks is important. With this understanding, we can work on new methods to enhance benefits and eliminate drawbacks. The overall outcome will be healthier human and animal populations over time. Copyright © 2021 by John Wiley & Sons, Inc. All rights reserved. 61 This OpenStax ancillary resource is © Rice University under a CC-BY 4.0 International license; it may be reproduced or modified but must be attributed to OpenStax, Rice University and any changes must be noted. ©John Wiley & Sons, Inc. or the author (Wessner et al, Microbiology). All rights reserved. Students and instructors who are authorized users of this course are permitted to download these materials and use them in connection with the course. No part of these materials should be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse this material is available at http://wiley.com/go/permissions openstax.org/details/books/microbiology Wessner, Microbiology, 3e