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33.1 Airborne Pathogens • Aerosols are important for person-to-person transmission of many infectious diseases • Most pathogens survive poorly in air, thus, are effectively transmitted only over short distances • Respiratory infections – Different pathogens characteristically colonize the respiratory tract at different levels – The upper and lower respiratory tracts offer different environments and favor different microbes © 2012 Pearson Education, Inc. Figure 33.1 © 2012 Pearson Education, Inc. 33.2 Streptococcal Diseases • Streptococcus pyogenes (group A Streptococcus; GAS) – Commonly found in low numbers in the upper respiratory tract of healthy individuals – Causative agent of “strep throat” – Can also cause infections of the inner ear, mammary glands, and skin • Infections occur if host defenses are weakened or a new, highly virulent strain is introduced © 2012 Pearson Education, Inc. Figure 33.3 © 2012 Pearson Education, Inc. Figure 33.4 © 2012 Pearson Education, Inc. Figure 33.5 © 2012 Pearson Education, Inc. 33.2 Streptococcal Diseases • Streptococcus pyogenes (cont’d) – Certain GAS strains carry a lysogenic bacteriophage that encodes exotoxins responsible for symptoms of toxic shock syndrome and scarlet fever – Untreated or insufficiently treated infections can lead to other diseases (e.g., rheumatic fever) © 2012 Pearson Education, Inc. Figure 33.6 © 2012 Pearson Education, Inc. 33.3 Diphtheria and Pertussis • Diphtheria – A severe respiratory disease that typically infects children – Caused by Corynebacterium diphtheriae • A bacterium that forms irregular rods during growth – Preventable and treatable © 2012 Pearson Education, Inc. Figure 33.7a © 2012 Pearson Education, Inc. 33.3 Diphtheria and Pertussis • Corynebacterium diphtheriae – Spreads by airborne droplets and enters the body via the respiratory route – Previous infection or immunization provides resistance – Pathogenic strains lysogenized by bacteriophage produce a powerful exotoxin that causes • Tissue death • The appearance of the pseudomembrane in the patient’s throat © 2012 Pearson Education, Inc. Figure 33.7b © 2012 Pearson Education, Inc. 33.3 Diphtheria and Pertussis • Diagnosis of Diphtheria – C. diphtheriae must be isolated from the throat • Prevention of Diphtheria – Vaccine • Treatment of Diphtheria – Antibiotics – Diphtheria antitoxin available for acute cases • Early administration necessary © 2012 Pearson Education, Inc. 33.3 Diphtheria and Pertussis • Pertussis (whooping cough) – – – – – An acute, highly infectious respiratory disease Caused by infection with Bordetella pertussis Observed frequently in school-age children Characterized by a recurrent, violent cough There has been a consistent upward trend of infections since the 1980s – Inadequately immunized children, adolescents, and adults are at high risk for acquiring and spreading pertussis © 2012 Pearson Education, Inc. Figure 33.8 Pertussis (incidence per 100,000 population) 9 8 7 6 5 4 3 2 1 0 1977 1982 1987 1992 Year © 2012 Pearson Education, Inc. 1997 2002 2007 33.3 Diphtheria and Pertussis • Diagnosis – Made by fluorescent antibody staining of a nasopharyngeal swab specimen – Also made by actual culture of the organism • Prevention – Vaccine soon after birth • Treatment – Antibiotics – But elimination is helped by the immune response © 2012 Pearson Education, Inc. 33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease • Tuberculosis is caused by Mycobacterium tuberculosis • Hansen’s disease (leprosy) is caused by Mycobacterium leprae • All mycobacteria are acid-fast due to the waxy mycolic acid content of their cell walls © 2012 Pearson Education, Inc. Figure 33.9 © 2012 Pearson Education, Inc. 33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease • Tuberculosis – – – – Worldwide infectious disease of humans Incidence is increasing M. tuberculosis transmitted by airborne droplets Cell-mediated immunity plays a critical role in the prevention of active disease after infection – Classified as a primary (initial) infection or postprimary infection (reinfection) © 2012 Pearson Education, Inc. Figure 33.10 © 2012 Pearson Education, Inc. 33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease • Spread of tuberculosis is prevented by – Hospitalization of patients in negative-pressure rooms – Use of face masks for healthcare workers • Treatment – Antimicrobial therapy with isoniazid • Treatment usually requires a 9-month regimen • Affects the synthesis of mycolic acid in mycobacteria © 2012 Pearson Education, Inc. 33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease • Hansen’s disease (leprosy) – M. leprae is the causative agent – The armadillo is the only experimental animal that has been successfully used to grow M. leprae – Most serious form is characterized by folded, bulblike lesions on the body © 2012 Pearson Education, Inc. Figure 33.12 © 2012 Pearson Education, Inc. 33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease • Pathogenicity of M. leprae – Due to a combination of delayed hypersensitivity and the invasiveness of the organism – Transmission is by both direct contact and respiratory routes – Incubation times vary from several weeks to years – The incidence of leprosy worldwide is low © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Viruses are less easily controlled by chemotherapeutic methods • The most prevalent human infections are caused by viruses • Most viral diseases are acute, self-limiting infections • A few serious viral diseases have been effectively controlled by vaccination (e.g., smallpox and rabies) © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Measles (rubeola or 7-day measles) – Often affects susceptible children as an acute, highly infectious, often epidemic disease (Figure 33.14) – Caused by a paramyxovirus • Negative-strand RNA virus – Virus enters the nose and throat by airborne transmission © 2012 Pearson Education, Inc. Figure 33.14 © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Measles (cont’d) – Used to be a common childhood illness – Now only occurs in rather isolated outbreaks • Due to widespread immunization programs that began in the mid-1960s – Over 600,000 deaths per year worldwide – Proof of immunization required for enrollment in U.S. public schools © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Mumps – – – – Caused by a paramyxovirus (like measles) Highly infectious Spread by airborne droplets Characterized by inflammation of the salivary glands © 2012 Pearson Education, Inc. Figure 33.16 © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Rubella (German measles or 3-day measles) – Caused by a positive-strand RNA virus of the togavirus group – Disease symptoms resemble measles but are generally milder and less contagious – Routine childhood immunization is practiced in the U.S. © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • In the U.S., the incidence of measles, mumps, and rubella has decreased significantly since the implementation of the MMR vaccine © 2012 Pearson Education, Inc. Cases per 100,000 population Figure 33.15 30 25 20 15 10 5 0 1987 400 Vaccine licensed 200 0 1965197019751980 1985 1992 1997 2002 2007 2012 Cases per 100,000 population Measles 7 6 5 4 3 2 1 0 1987 150 100 50 0 19651970197519801985 1992 1997 2002 2007 2012 Cases per 100,000 population Mumps 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 1987 Rubella © 2012 Pearson Education, Inc. 20 10 0 1960 19651970197519801985 1992 1997 2002 2007 2012 33.6 Viruses and Respiratory Infections • Chicken pox (varicella) – Common childhood disease characterized by a systemic papular rash – Caused by varicella-zoster virus (VZV), a herpesvirus – VZV is highly contagious and transmitted by infectious droplets – A vaccine is presently used in the U.S. © 2012 Pearson Education, Inc. Figure 33.17 © 2012 Pearson Education, Inc. 33.6 Viruses and Respiratory Infections • Chicken pox (cont’d) – VZV virus establishes a lifelong latent infection in nerve cells – The virus occasionally migrates to the skin surface, causing a painful skin eruption (shingles) © 2012 Pearson Education, Inc. 33.7 Colds • Colds – Viral infections transmitted via airborne droplets – Infections are usually of short duration – Symptoms milder than other respiratory diseases – Symptoms include rhinitis, nasal obstruction, watery nasal discharges, and malaise © 2012 Pearson Education, Inc. Figure 33.18 All other infectious diseases Colds Influenza 0 100 200 300 Cases per 100 people per year © 2012 Pearson Education, Inc. 400 33.7 Colds • The Common Cold – Commonly caused by rhinoviruses (Figure 33.19) • Positive-sense, single-stranded RNA viruses • Nearly 115 different strains identified – Approximately 15% of colds are due to coronaviruses – Approximately 10% of colds are due to other viruses © 2012 Pearson Education, Inc. Figure 33.19 © 2012 Pearson Education, Inc. 33.7 Colds • Each cold infection induces a specific, protective immunity, but the large number of viral cold pathogens precludes complete protective immunity or vaccines © 2012 Pearson Education, Inc. 33.8 Influenza • Influenza is caused by an RNA virus of the orthomyxovirus group • There are three different types of influenza viruses (A, B, C) • Influenza A is the most important human pathogen © 2012 Pearson Education, Inc. Figure 33.21 HA trimer Lipid bilayer M protein NA tetramer RNA NP PA, PB1, PB2 © 2012 Pearson Education, Inc. 33.8 Influenza • Influenza outbreaks occur annually due to the plasticity of the influenza genome – Antigenic shift • Major change in influenza virus antigen due to gene reassortment (Figure 33.22) – Antigenic drift • Minor change in influenza virus antigens due to gene mutation © 2012 Pearson Education, Inc. Figure 33.22 Bird virus Reassortant Human virus virus Infection with human virus Infection with bird virus Reassortment of human and bird virus © 2012 Pearson Education, Inc. Infection with reassortant virus 33.8 Influenza • Influenza epidemics and pandemics occur periodically – 1957 outbreak of Asian flu – 1997 outbreak of avian influenza © 2012 Pearson Education, Inc. Figure 33.23 Country of origin Countrywide epidemic Localized outbreaks Routes of spread © 2012 Pearson Education, Inc. 33.8 Influenza • Prevention – Immunization – Careful worldwide surveillance • Treatment – Use of various drugs – Most effective when administered early – Aspirin should be avoided © 2012 Pearson Education, Inc. 33.11 Hepatitis Viruses • Hepatitis – Liver inflammation caused by viruses or bacteria – Sometimes results in acute illness followed by destruction of liver anatomy and cells (cirrhosis) – A restricted group of viruses is associated with liver disease – Hepatitis viruses are diverse © 2012 Pearson Education, Inc. 33.11 Hepatitis Viruses • Hepatitis A virus (infectious hepatitis) – Causes mild or, rarely, severe cases of liver disease • Hepatitis B virus (serum hepatitis; Figure 33.27) – Causes acute, often severe disease that can lead to liver failure and death • Hepatitis D virus – A defective virus that cannot replicate and express a complete virus unless the cell is also infected with hepatitis B © 2012 Pearson Education, Inc. Figure 33.27 © 2012 Pearson Education, Inc. 33.11 Hepatitis Viruses • Hepatitis C virus – Produces a mild disease initially, but most individuals develop chronic hepatitis that can lead to chronic liver disease © 2012 Pearson Education, Inc. 33.11 Hepatitis Viruses • Incidence and Prevalence of Hepatitis – Decreased significantly in the U.S. in the last 20 years (Figure 33.26) – Viral hepatitis is still a major public health problem • Due to the high infectivity of the viruses and the lack of effective treatment options – Vaccines are available for Hepatitis A and B viruses © 2012 Pearson Education, Inc. Figure 33.26 Cases per 100,000 population 20 HBV vaccine 1982 HAV vaccine 1995 Hepatitis A Hepatitis B Hepatitis C 15 10 5 0 1975 1980 1985 1990 Year © 2012 Pearson Education, Inc. 1995 2000 2005 2010 III. Sexually Transmitted Infections • Sexually Transmitted Infections (STIs) – Also called sexually transmitted diseases (STDs) or venereal diseases – Caused by a variety of bacteria, viruses, protists, and even fungi – Pathogens are generally only found in body fluids from the genitourinary tract that are exchanged during sexual activity © 2012 Pearson Education, Inc. 33.12 Gonorrhea and Syphilis • Gonorrhea and syphilis are preventable, treatable bacterial STIs • The overall pattern of disease differs between the two – Gonorrhea is prevalent and often asymptomatic in women – Syphilis has low prevalence and exhibits very obvious symptoms © 2012 Pearson Education, Inc. Reported cases per 100,000 population Figure 33.28 500 400 World War II Birth control pills Syphilis 300 Gonorrhea 200 100 Penicillin 0 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 © 2012 Pearson Education, Inc. Year 33.12 Gonorrhea and Syphilis • Gonorrhea – Caused by Neisseria gonorrhoeae – Symptoms in females • Characterized by a mild vaginitis that often goes unnoticed • Untreated gonorrhea can lead to pelvic inflammatory disease – Symptoms in males • Characterized by a painful infection of the urethral canal © 2012 Pearson Education, Inc. Figure 33.29 © 2012 Pearson Education, Inc. 33.12 Gonorrhea and Syphilis • Syphilis – Caused by Treponema pallidum – Often transmitted at the same time as gonorrhea – T. pallidum can be transmitted from an infected woman to the fetus during pregnancy (congenital syphilis) – Three stages: primary, secondary, and tertiary – Penicillin highly effective for primary and secondary stages © 2012 Pearson Education, Inc. Figure 33.30 © 2012 Pearson Education, Inc. 33.13 Chlamydia, Herpes, and HPV • Chlamydia trachomatis causes a number of sexually transmitted diseases – Nongonococcal urethritis (NGU) – Lymphogranuloma venereum © 2012 Pearson Education, Inc. Figure 33.32 © 2012 Pearson Education, Inc. 33.13 Chlamydia, Herpes, Trichomoniasis, and HPV • Herpes simplex 1 virus (HSV-1) – Infects the epithelial cells around the mouth and lips – Causes cold sores – May occasionally affect other body sites – Spread via direct contact or through saliva – Lesions heal without treatment in 2 to 3 weeks © 2012 Pearson Education, Inc. 33.13 Chlamydia, Herpes, Trichomoniasis, and HPV • Herpes simplex 2 virus (HSV-2) – Infections are associated primarily with anogenital region – Causes painful blisters on penis of male and cervix, vulva, or vagina of females – Typically transmitted through sexual contact and most easily transmitted when active blisters are present – Genital herpes are presently incurable, however, a limited number of drugs are successful in controlling the infectious blister stage © 2012 Pearson Education, Inc. 33.13 Chlamydia, Herpes, Trichomoniasis, and HPV • Human papillomavirus (HPV) – Causes several different infections • Many infections are asymptomatic but some progress to genital warts • Can cause cervical neoplasia, and a few progress to cervical cancers – There is an effective HPV vaccine © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • AIDS – Recognized as a distinct disease in 1981 – Human immunodeficiency virus (HIV) is the causative agent • HIV – As many as 1.4 million people worldwide may be infected © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • HIV is divided into two types: – HIV-1 is the more virulent type – HIV-2 is less virulent and causes a milder, AIDSlike disease • Opportunistic infections are common in AIDS patients © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • A frequent nonmicrobial disease in AIDS patients is Kaposi’s sarcoma, an atypical cancer © 2012 Pearson Education, Inc. Figure 33.37 © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • HIV Pathogenesis – HIV infects cells that contain the CD4 cell surface protein – Most commonly infected are macrophages and T-helper cells – HIV also interacts with coreceptors on target cells © 2012 Pearson Education, Inc. Figure 33.38 Mature form Budding particles © 2012 Pearson Education, Inc. Figure 33.39 HIV gp120 protein binds CD4 receptor and CCR5 receptor Interaction of the virus with a receptor– coreceptor pair on the host cell The viral envelope and host membrane coalesce The nucleocapsid is inserted into the host cell, beginning the viral infection Nucleocapsid HIV gp 120 CD4 CCR5 Target cell Nucleus Interaction of HIV with a host cell © 2012 Pearson Education, Inc. Fusion of the HIV envelope with the host cell 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • HIV infection does not immediately kill the host cell • Infection results in a progressive decline in CD4 cells • As the number of CD4 cells declines, cytokine production falls, leading to reduction of the immune response © 2012 Pearson Education, Inc. Figure 33.40 Subclinical immune dysfunction Symptom- Swollen lymph glands free 1000 Systemic Opporimmune tunistic infections deficiency 106 900 Normal range for T cells Significantly depressed T cells Severe T cell depletion 800 700 CD4 T cells 600 per 500 mm3 of blood 400 104 Death 102 300 200 100 0 0 6 12 18 24 30 36 42 48 54 60 Time (months) after HIV exposure © 2012 Pearson Education, Inc. 66 72 78 84 HIV RNA copies per ml 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • HIV infection can be diagnosed with an HIV-EIA, HIV-immunoblot, or rapid tests – These fail to detect infection in individuals who recently acquired the HIV and have not made a detectable antibody • RT-PCR can detect HIV RNA directly from blood and estimate the number of viruses present – This is useful for early detection and monitoring the progression of infection © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • Treatment – Four classes of drugs delay the symptoms of AIDS and prolong the life of those infected with HIV • • • • Nucleoside reverse transcriptase inhibitors Nonnucleoside reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors – Highly active antiretroviral therapy (HAART) is used © 2012 Pearson Education, Inc. 33.14 Acquired Immunodeficiency Syndrome: AIDS & HIV • There is not an effective vaccine for HIV • Prevention for the spread of HIV infection requires education and avoidance of high-risk behavior © 2012 Pearson Education, Inc.