Handbook of Clinical Neurology, Vol. 123 (3rd series) Neurovirology A.C. Tselis and J. Booss, Editors © 2014 Elsevier B.V. All rights reserved
Chapter 36
Vaccines and viral / toxin-associated neurologic infections JAMES SEJVAR* Division of Viral and Rickettsial Diseases, Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
INTRODUCTION Among the medical milestones of human history, the discovery and implementation of vaccines have undoubtedly ranked among the top; the development of vaccines against various infectious diseases has ameliorated uncountable morbidity and mortality worldwide. Despite its relatively recent emergence, vaccination has successfully controlled at least 12 major diseases in most of the world, and has successfully eradicated one – smallpox – from the globe. The nature by which vaccines work, however – by stimulation of the innate immune system – carries with it the risk of rare adverse events. This chaptr will explore the various neurologicassociated infections that have been controlled by vaccines and also explore the occurrence of rare neurologic adverse events associated with vaccination.
VACCINES AND VACCINE IMMUNOLOGY Vaccines produce an antigen-specific immune response against a virulent infectious agent without actually causing disease. The ability to achieve this was first demonstrated scientifically by Edward Jenner in the late 1700s, when he inoculated a young boy with cowpox virus material, a less virulent relative of the deadly smallpox virus. When the boy was subsequently inoculated with fully virulent material from a smallpox lesion, the child did not develop disease. Vaccines effect their immune protection primarily by stimulation of B lymphocytes to produce antibodies that are capable of binding specifically to a toxin or pathogen (Plotkin et al., 2008). With rare exceptions, vaccines also stimulate the activity of CD4 þ T cells (T-helper cells) which support the differentiation of B cells. In some
vaccines, a CD8 þ T-cell response develops in parallel with the B-cell response, resulting in T cells capable of killing infected cells, a process that is particularly important with live-attenuated vaccines. Vaccination ultimately results in the formation of antigen-specific immunoglobulin G (IgG) antibodies, thus conferring protection. There are several different types of vaccines, which can essentially be broken down into live and inactivated vaccines. Live vaccines involve the attenuation of disease-causing viruses by serial passage in cells or tissues from other species, which results in adaptation of the pathogen to the tissue of the other species and thus renders it less virulent to human cells. This attenuated organism is able to infect and replicate in human cells, but results in a mild or subclinical infection that produces immunity against wild-type virus that would be encountered in nature. Such live-attenuated vaccines effectively trigger strong activation of the innate immune system, generally resulting in higher immunogenicity. Inactivated vaccines come in several different forms, and can include “killed” whole virus or bacteria, proteins, polysaccharides, glycoconjugates, or toxoids. “Killed” vaccines involve inactivation of microorganisms through exposure to chemical or physical agents that render the organism non-infectious and unable to replicate. Protein or polysaccharide vaccines essentially entail the inclusion of epitopes associated with a microorganism or toxin that are readily recognized by B cells and T-helper cells, allowing for a specific IgG response to these proteins/polysaccharides. The conjugation of bacterial polysaccharides to a protein carrier (e.g., glycoconjugated vaccines) provides foreign peptide antigens within the vaccine that allow for recruitment of antigen-specific CD4 þ T-helper cells, producing a
*Correspondence to: James Sejvar, M.D., Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333, USA. Tel: þ1-404-639-4657, Fax: þ1-404-639-3838, E-mail: [email protected]
720
J. SEJVAR
T-dependent antibody response, a response not possible with bacterial polysaccharides alone. Toxoid vaccines include bacterial toxins (tetanus, diphtheria) that have been chemically treated to be rendered immunogenic, but non-pathogenic. More recently, several additional vaccine technologies have become available. Nucleic acid-based vaccines entail the use of DNA which encodes a vaccine antigen. The in vitro model for this approach involves the transformation of cells in culture with a plasmid that directs the synthesis of a vaccine antigen. After cells in vivo take up DNA encoding the vaccine antigens, the antigens can be secreted or incorporated into the cell surface and produce a humoral or cellular immune response. The initial strategy for this has been to inject intramuscularly a solution of uncoated (“naked”) DNA encoding a vaccine antigen; cells then take up the DNA, transcribe and synthesize the antigen, and process it similarly to a live viral infection, producing a humoral or cellular immune response to the encoded antigen (Wolff et al., 1990). Facilitation of DNA incorporation may be achieved at several different levels in the process. Alternatively, plasmid expression may be achieved by incorporating a vaccine antigen plasmid into a nonpathogenic viral “vector.” During infection with the non-pathogenic vector, protein from the DNA of the virulent microorganism is also presented to the immune system without infection by the virulent organism (Liu, 2010). This technique has been explored in the development of vaccines for various flaviviruses, malaria, and other pathogens (Sukumaran and Madhubala, 2004; Blair et al., 2006; Gao et al., 2009; Najera et al., 2010). There are several important determinants of vaccine efficacy which modulate the intensity of peak antibody responses. The nature of the vaccine antigen and its intrinsic immunogenicity are important, with some antigens being inherently more immunogenic than others. Live vaccines generally elicit stronger innate immune responses and thus stronger antibody responses. Nonlive vaccines frequently require the use of adjuvants, or agents which increase the stimulation of the immune system by enhancing antigen presentation; aluminum salts are frequently used as adjuvants (Coffman et al., 2010). Many vaccines, particularly inactivated vaccines, require multiple doses to induce high and sustained antibody responses, or may require repeated administration at particular intervals. Antibody persistence is critically important; for the vaccine immune response to last, memory B cells, which are capable of recognizing and responding to an antigen challenge and subsequently proliferating and differentiating into antibodyproducing plasma cells, must be produced. Antibody persistence may be dependent on several different determinants, including the nature of the vaccine (live versus
inactivated), interval between doses, and age at immunization. Vaccines may be used in various different scenarios or situations. Many vaccines are widely used and are given in childhood to prevent various childhood infections (e.g., measles, mumps, rubella). Vaccine schedules can be found on the Centers for Disease Control and Prevention (CDC) website at http://www.cdc.gov/ vaccines/recs/schedules/downloads/child/2011/mmwrchild-schedule.pdf (Centers for Disease Control and Prevention, 2011b). Some vaccines are given predominantly in the setting of a suspected exposure to a particular infectious agent (e.g., rabies vaccine in the setting of an animal exposure). Some vaccines are used in particular settings, such as in attempts to control an outbreak of disease; this is true, for instance, with typhoid and cholera vaccines. In the United States and elsewhere, some vaccines are reserved for travelers to an area endemic for a particular pathogen, for instance, yellow fever or Japanese encephalitis vaccines (Centers for Disease Control and Prevention, 2009b). Finally, some vaccines are reserved for persons with particular risks for exposure and are not widely available, for instance vaccines against Venezuelan equine encephalitis (VEE) virus (Paessler and Weaver, 2009).
VACCINES FOR NEUROLOGIC INFECTIONS (TABLE 36.1) Effective vaccines exist for a number of neurologic infections. This includes infections in which neurologic illness may occasionally be a manifestation of infection (measles, mumps, varicella, smallpox), as well as those in which neurologic disease is the primary feature (Japanese encephalitis, rabies, polio). Additionally, toxoid vaccines against bacterial toxins resulting in neurologic illness have been developed and are important and effective interventions for toxin-mediated neurologic diseases (Advisory Committee for Immunization Practices, 2011).
Vaccines for infections occasionally resulting in neurologic disease In some cases, infections associated with other prominent clinical syndromes, such as rash illness, pneumonia, or other manifestations, may result in neurologic illness. Effective vaccines have substantially decreased the overall burden of morbidity and mortality from these agents, including that due to neurologic illness.
MEASLES Measles is a febrile rash illness caused by measles virus, a negative-stranded RNA paramyxovirus. It is a highly
Table 36.1 Vaccines for neurologic infections
Disease Viral diseases Influenza
Organism / agent
Neurologic syndrome(s)
Vaccine type(s)
Vaccine formulation(s)
Representative indications
TIV, LAIV*: All persons 6 months of age should be vaccinated. When vaccine supply is limited, then high-risk groups should be targeted{ Routine childhood vaccination (worldwide) Immunization of persons without evidence of immunity
Routine childhood vaccinations (worldwide) Immunization of persons without evidence of immunity Routine childhood vaccination (worldwide) Immunization of persons without evidence of immunity Vaccination of seronegative pregnant women IPV: Routine childhood vaccination in children in North America, Europe, Australia, New Zealand; booster to adults traveling to polioendemic countries{ OPV: Routine childhood immunization of children in developing or polio-endemic countries; control of outbreaks; use in national / subnational immunization campaigns{ Semple, Fuenzalida: Postexposure prophylaxis, only used in Asia,
Single-stranded RNA orthomyxovirus
Influenza-associated encephalopathy (rare)
Inactivated (trivalent inactivated vaccine, TIV) Live-attenuated influenza vaccine (LAIV)
Measles
Negative-stranded RNA paramyxovirus
Live-attenuated
Mumps
Negative-stranded RNA paramyxovirus
Encephalitis, cerebellitis, aseptic meningitis; subacute sclerosing panencephalitis (SSPE) (rare) Encephalitis, aseptic meningitis, cerebellitis
TIV, LAIV – various manufacturers; includes most commonly circulating influenza viruses; reformulated seasonally Measles, MMR
Live-attenuated
Measles, MMR
Rubella
Positive-stranded RNA togavirus
Live-attenuated
Measles, MMR
Polio
Positive-stranded RNA picornavirus
Postinfectious encephalitis; progressive rubella panencephalitis (PRP) (rare); congenital rubella Aseptic meningitis; anterior myelitis producing acute flaccid paralysis (AFP)
Live-attenuated oral polio vaccine (OPV) Inactivated intramuscular polio vaccine (IPV)
OPV (various manufacturers) IPV (various manufacturers)
Rabies
Negative-stranded RNA rhabdovirus
Inactivated, nerve-tissue derived (Semple,
Continued
Table 36.1 Continued
Disease
Organism / agent
Neurologic syndrome(s) Progressive, fatal rhomboencephalitis; peripheral neuritis
Vaccine type(s)
Vaccine formulation(s)
Fuenzalida); inactivated, purified chick embryo cell derived (PCECV) or purified duck embryo cell vaccine (PDECV); inactivated, cell culturederived (various cell lines)
Japanese encephalitis
Positive-stranded RNA flavivirus
Inactivated, mouse brainAseptic meningitis, derived; encephalitis, anterior Vero cell vaccine: myelitis Inactivated, PHKC-derived; Live-attenuated, PHKCderived
Tick-borne encephalitis
Positive-stranded RNA flavivirus
Inactivated, PCEC-derived Aseptic meningitis, encephalitis, anterior myelitis
FSME-Immun (Baxter){ParaMarks} (Europe, Canada) Encepur (Novartis) (Europe)
Eastern / Western / Venezuelan equine encephalitis (EEE/ WEE/VEE)
Positive-stranded RNA togavirus (all)
Aseptic meningitis, encephalitis
Inactivated Live-attenuated (VEE only)
Varicella-zoster
Double-stranded DNA herpesvirus
Cerebellitis, encephalitis
Live-attenuated
Inactivated: VEE TC-83; EEE TSI-GSD-104; WEE TSIGSD-210 Live-attenuated: VEE TC-83 (live) MMRV (Proquad{ParaMarks}, Merck), V (various manufacturers)
Representative indications Africa (Semple), and South America (Fuenzalida) PDECV, PCECV, cell line culture derived: postexposure prophylaxis; pre-exposure vaccination in high-risk persons (veterinarians, hunters, dog catchers); pre-exposure vaccination in travelers to rabiesendemic countries for long durations of time Vaccination for children in endemic areas Vaccination for other susceptible persons in endemic areas Vaccination for travelers to endemic areas with significant risk of exposure Vaccination for children, at-risk persons in endemic areas} Vaccination for travelers to endemic areas with significant risk exposure Limited use, not available to general public Vaccination of military personnel, laboratory workers Routine childhood vaccination in North America, Europe, Australia, New Zealand Immunization of targeted populations (healthcare workers, immunosuppressed, adults
Herpes zoster
Toxoid vaccines Tetanus
Diphtheria
Double-stranded DNA herpesvirus
Latent infection with varicella-zoster virus, resulting in ganglionitis with painful erythematous eruption; postherpetic neuralgia
Localized or, more Tetanospasmin, a commonly, 150 kDa polypeptide generalized spasms, toxin produced by hyperreflexia, Clostridium tetani, a trismus, autonomic Gram-positive, instability spore-forming bacillus Palatal and facial Diphtheria toxin, a paralysis; 58 kDa polypeptide generalized exotoxin secreted by peripheral Corynebacterium neuropathy diphtheriae, a Gram(uncommon) positive bacillus
without immunity, persons living / working in environments with reported or likely transmission, international travelers) Recommended for persons over age 60, regardless of prior episode of herpes zoster
Live-attenuated
Zostavax{ParaMarks}(Merck)
Inactivated toxoid
Td}, DT**, DTP, DTaP, Tdap Routine childhood vaccination in (various manufacturers) most of the world Booster doses every 10 years generally recommended Postexposure wound prophylaxis in certain situations
Inactivated toxoid
Td, DT, DTP, DTaP, Tdap (various manufacturers)
Routine childhood vaccination in children
Chapter 36
Vaccines and viral / toxin-associated neurologic infections JAMES SEJVAR* Division of Viral and Rickettsial Diseases, Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
INTRODUCTION Among the medical milestones of human history, the discovery and implementation of vaccines have undoubtedly ranked among the top; the development of vaccines against various infectious diseases has ameliorated uncountable morbidity and mortality worldwide. Despite its relatively recent emergence, vaccination has successfully controlled at least 12 major diseases in most of the world, and has successfully eradicated one – smallpox – from the globe. The nature by which vaccines work, however – by stimulation of the innate immune system – carries with it the risk of rare adverse events. This chaptr will explore the various neurologicassociated infections that have been controlled by vaccines and also explore the occurrence of rare neurologic adverse events associated with vaccination.
VACCINES AND VACCINE IMMUNOLOGY Vaccines produce an antigen-specific immune response against a virulent infectious agent without actually causing disease. The ability to achieve this was first demonstrated scientifically by Edward Jenner in the late 1700s, when he inoculated a young boy with cowpox virus material, a less virulent relative of the deadly smallpox virus. When the boy was subsequently inoculated with fully virulent material from a smallpox lesion, the child did not develop disease. Vaccines effect their immune protection primarily by stimulation of B lymphocytes to produce antibodies that are capable of binding specifically to a toxin or pathogen (Plotkin et al., 2008). With rare exceptions, vaccines also stimulate the activity of CD4 þ T cells (T-helper cells) which support the differentiation of B cells. In some
vaccines, a CD8 þ T-cell response develops in parallel with the B-cell response, resulting in T cells capable of killing infected cells, a process that is particularly important with live-attenuated vaccines. Vaccination ultimately results in the formation of antigen-specific immunoglobulin G (IgG) antibodies, thus conferring protection. There are several different types of vaccines, which can essentially be broken down into live and inactivated vaccines. Live vaccines involve the attenuation of disease-causing viruses by serial passage in cells or tissues from other species, which results in adaptation of the pathogen to the tissue of the other species and thus renders it less virulent to human cells. This attenuated organism is able to infect and replicate in human cells, but results in a mild or subclinical infection that produces immunity against wild-type virus that would be encountered in nature. Such live-attenuated vaccines effectively trigger strong activation of the innate immune system, generally resulting in higher immunogenicity. Inactivated vaccines come in several different forms, and can include “killed” whole virus or bacteria, proteins, polysaccharides, glycoconjugates, or toxoids. “Killed” vaccines involve inactivation of microorganisms through exposure to chemical or physical agents that render the organism non-infectious and unable to replicate. Protein or polysaccharide vaccines essentially entail the inclusion of epitopes associated with a microorganism or toxin that are readily recognized by B cells and T-helper cells, allowing for a specific IgG response to these proteins/polysaccharides. The conjugation of bacterial polysaccharides to a protein carrier (e.g., glycoconjugated vaccines) provides foreign peptide antigens within the vaccine that allow for recruitment of antigen-specific CD4 þ T-helper cells, producing a
*Correspondence to: James Sejvar, M.D., Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333, USA. Tel: þ1-404-639-4657, Fax: þ1-404-639-3838, E-mail: [email protected]
720
J. SEJVAR
T-dependent antibody response, a response not possible with bacterial polysaccharides alone. Toxoid vaccines include bacterial toxins (tetanus, diphtheria) that have been chemically treated to be rendered immunogenic, but non-pathogenic. More recently, several additional vaccine technologies have become available. Nucleic acid-based vaccines entail the use of DNA which encodes a vaccine antigen. The in vitro model for this approach involves the transformation of cells in culture with a plasmid that directs the synthesis of a vaccine antigen. After cells in vivo take up DNA encoding the vaccine antigens, the antigens can be secreted or incorporated into the cell surface and produce a humoral or cellular immune response. The initial strategy for this has been to inject intramuscularly a solution of uncoated (“naked”) DNA encoding a vaccine antigen; cells then take up the DNA, transcribe and synthesize the antigen, and process it similarly to a live viral infection, producing a humoral or cellular immune response to the encoded antigen (Wolff et al., 1990). Facilitation of DNA incorporation may be achieved at several different levels in the process. Alternatively, plasmid expression may be achieved by incorporating a vaccine antigen plasmid into a nonpathogenic viral “vector.” During infection with the non-pathogenic vector, protein from the DNA of the virulent microorganism is also presented to the immune system without infection by the virulent organism (Liu, 2010). This technique has been explored in the development of vaccines for various flaviviruses, malaria, and other pathogens (Sukumaran and Madhubala, 2004; Blair et al., 2006; Gao et al., 2009; Najera et al., 2010). There are several important determinants of vaccine efficacy which modulate the intensity of peak antibody responses. The nature of the vaccine antigen and its intrinsic immunogenicity are important, with some antigens being inherently more immunogenic than others. Live vaccines generally elicit stronger innate immune responses and thus stronger antibody responses. Nonlive vaccines frequently require the use of adjuvants, or agents which increase the stimulation of the immune system by enhancing antigen presentation; aluminum salts are frequently used as adjuvants (Coffman et al., 2010). Many vaccines, particularly inactivated vaccines, require multiple doses to induce high and sustained antibody responses, or may require repeated administration at particular intervals. Antibody persistence is critically important; for the vaccine immune response to last, memory B cells, which are capable of recognizing and responding to an antigen challenge and subsequently proliferating and differentiating into antibodyproducing plasma cells, must be produced. Antibody persistence may be dependent on several different determinants, including the nature of the vaccine (live versus
inactivated), interval between doses, and age at immunization. Vaccines may be used in various different scenarios or situations. Many vaccines are widely used and are given in childhood to prevent various childhood infections (e.g., measles, mumps, rubella). Vaccine schedules can be found on the Centers for Disease Control and Prevention (CDC) website at http://www.cdc.gov/ vaccines/recs/schedules/downloads/child/2011/mmwrchild-schedule.pdf (Centers for Disease Control and Prevention, 2011b). Some vaccines are given predominantly in the setting of a suspected exposure to a particular infectious agent (e.g., rabies vaccine in the setting of an animal exposure). Some vaccines are used in particular settings, such as in attempts to control an outbreak of disease; this is true, for instance, with typhoid and cholera vaccines. In the United States and elsewhere, some vaccines are reserved for travelers to an area endemic for a particular pathogen, for instance, yellow fever or Japanese encephalitis vaccines (Centers for Disease Control and Prevention, 2009b). Finally, some vaccines are reserved for persons with particular risks for exposure and are not widely available, for instance vaccines against Venezuelan equine encephalitis (VEE) virus (Paessler and Weaver, 2009).
VACCINES FOR NEUROLOGIC INFECTIONS (TABLE 36.1) Effective vaccines exist for a number of neurologic infections. This includes infections in which neurologic illness may occasionally be a manifestation of infection (measles, mumps, varicella, smallpox), as well as those in which neurologic disease is the primary feature (Japanese encephalitis, rabies, polio). Additionally, toxoid vaccines against bacterial toxins resulting in neurologic illness have been developed and are important and effective interventions for toxin-mediated neurologic diseases (Advisory Committee for Immunization Practices, 2011).
Vaccines for infections occasionally resulting in neurologic disease In some cases, infections associated with other prominent clinical syndromes, such as rash illness, pneumonia, or other manifestations, may result in neurologic illness. Effective vaccines have substantially decreased the overall burden of morbidity and mortality from these agents, including that due to neurologic illness.
MEASLES Measles is a febrile rash illness caused by measles virus, a negative-stranded RNA paramyxovirus. It is a highly
Table 36.1 Vaccines for neurologic infections
Disease Viral diseases Influenza
Organism / agent
Neurologic syndrome(s)
Vaccine type(s)
Vaccine formulation(s)
Representative indications
TIV, LAIV*: All persons 6 months of age should be vaccinated. When vaccine supply is limited, then high-risk groups should be targeted{ Routine childhood vaccination (worldwide) Immunization of persons without evidence of immunity
Routine childhood vaccinations (worldwide) Immunization of persons without evidence of immunity Routine childhood vaccination (worldwide) Immunization of persons without evidence of immunity Vaccination of seronegative pregnant women IPV: Routine childhood vaccination in children in North America, Europe, Australia, New Zealand; booster to adults traveling to polioendemic countries{ OPV: Routine childhood immunization of children in developing or polio-endemic countries; control of outbreaks; use in national / subnational immunization campaigns{ Semple, Fuenzalida: Postexposure prophylaxis, only used in Asia,
Single-stranded RNA orthomyxovirus
Influenza-associated encephalopathy (rare)
Inactivated (trivalent inactivated vaccine, TIV) Live-attenuated influenza vaccine (LAIV)
Measles
Negative-stranded RNA paramyxovirus
Live-attenuated
Mumps
Negative-stranded RNA paramyxovirus
Encephalitis, cerebellitis, aseptic meningitis; subacute sclerosing panencephalitis (SSPE) (rare) Encephalitis, aseptic meningitis, cerebellitis
TIV, LAIV – various manufacturers; includes most commonly circulating influenza viruses; reformulated seasonally Measles, MMR
Live-attenuated
Measles, MMR
Rubella
Positive-stranded RNA togavirus
Live-attenuated
Measles, MMR
Polio
Positive-stranded RNA picornavirus
Postinfectious encephalitis; progressive rubella panencephalitis (PRP) (rare); congenital rubella Aseptic meningitis; anterior myelitis producing acute flaccid paralysis (AFP)
Live-attenuated oral polio vaccine (OPV) Inactivated intramuscular polio vaccine (IPV)
OPV (various manufacturers) IPV (various manufacturers)
Rabies
Negative-stranded RNA rhabdovirus
Inactivated, nerve-tissue derived (Semple,
Continued
Table 36.1 Continued
Disease
Organism / agent
Neurologic syndrome(s) Progressive, fatal rhomboencephalitis; peripheral neuritis
Vaccine type(s)
Vaccine formulation(s)
Fuenzalida); inactivated, purified chick embryo cell derived (PCECV) or purified duck embryo cell vaccine (PDECV); inactivated, cell culturederived (various cell lines)
Japanese encephalitis
Positive-stranded RNA flavivirus
Inactivated, mouse brainAseptic meningitis, derived; encephalitis, anterior Vero cell vaccine: myelitis Inactivated, PHKC-derived; Live-attenuated, PHKCderived
Tick-borne encephalitis
Positive-stranded RNA flavivirus
Inactivated, PCEC-derived Aseptic meningitis, encephalitis, anterior myelitis
FSME-Immun (Baxter){ParaMarks} (Europe, Canada) Encepur (Novartis) (Europe)
Eastern / Western / Venezuelan equine encephalitis (EEE/ WEE/VEE)
Positive-stranded RNA togavirus (all)
Aseptic meningitis, encephalitis
Inactivated Live-attenuated (VEE only)
Varicella-zoster
Double-stranded DNA herpesvirus
Cerebellitis, encephalitis
Live-attenuated
Inactivated: VEE TC-83; EEE TSI-GSD-104; WEE TSIGSD-210 Live-attenuated: VEE TC-83 (live) MMRV (Proquad{ParaMarks}, Merck), V (various manufacturers)
Representative indications Africa (Semple), and South America (Fuenzalida) PDECV, PCECV, cell line culture derived: postexposure prophylaxis; pre-exposure vaccination in high-risk persons (veterinarians, hunters, dog catchers); pre-exposure vaccination in travelers to rabiesendemic countries for long durations of time Vaccination for children in endemic areas Vaccination for other susceptible persons in endemic areas Vaccination for travelers to endemic areas with significant risk of exposure Vaccination for children, at-risk persons in endemic areas} Vaccination for travelers to endemic areas with significant risk exposure Limited use, not available to general public Vaccination of military personnel, laboratory workers Routine childhood vaccination in North America, Europe, Australia, New Zealand Immunization of targeted populations (healthcare workers, immunosuppressed, adults
Herpes zoster
Toxoid vaccines Tetanus
Diphtheria
Double-stranded DNA herpesvirus
Latent infection with varicella-zoster virus, resulting in ganglionitis with painful erythematous eruption; postherpetic neuralgia
Localized or, more Tetanospasmin, a commonly, 150 kDa polypeptide generalized spasms, toxin produced by hyperreflexia, Clostridium tetani, a trismus, autonomic Gram-positive, instability spore-forming bacillus Palatal and facial Diphtheria toxin, a paralysis; 58 kDa polypeptide generalized exotoxin secreted by peripheral Corynebacterium neuropathy diphtheriae, a Gram(uncommon) positive bacillus
without immunity, persons living / working in environments with reported or likely transmission, international travelers) Recommended for persons over age 60, regardless of prior episode of herpes zoster
Live-attenuated
Zostavax{ParaMarks}(Merck)
Inactivated toxoid
Td}, DT**, DTP, DTaP, Tdap Routine childhood vaccination in (various manufacturers) most of the world Booster doses every 10 years generally recommended Postexposure wound prophylaxis in certain situations
Inactivated toxoid
Td, DT, DTP, DTaP, Tdap (various manufacturers)
Routine childhood vaccination in children
