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 Figure 33.1 High-speed photograph of an unstifled sneeze. © 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 Figure 33.3 Streptococcus pathogens. © 2012 Pearson Education, Inc.

Figure 33.4 Figure 33.4 Typical lesions of impetigo. © 2012 Pearson Education, Inc.

Figure 33.5 Figure 33.5 Erysipelas. © 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 Figure 33.6 Scarlet fever. © 2012 Pearson Education, Inc.

33.3 Diphtheria and Pertussis 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 Figure 33.7 Corynebacterium and diphtheria. © 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 Figure 33.7 Corynebacterium and diphtheria. © 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.

Pertussis (incidence per 100,000 population) Figure 33.8 9 8 7 6 Pertussis (incidence per 100,000 population) 5 4 3 2 Figure 33.8 Bordetella and pertussis. 1 1977 1982 1987 1992 1997 2002 2007 Year © 2012 Pearson Education, Inc.

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 Figure 33.9 Mycobacteria. © 2012 Pearson Education, Inc.

33.4 Mycobacterium, Tuberculosis, and Hansen’s Disease 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 Figure 33.10 Tuberculosis X-ray. © 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 Figure 33.12 Lepromatous leprosy lesions on the skin. © 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 Figure 33.14 Measles in children. © 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 Figure 33.16 Mumps. © 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.

Measles Mumps Rubella Figure 33.15 30 25 Vaccine licensed 20 400 Cases per 100,000 population 15 200 10 5 1965 1970 1975 1980 1985 1987 1992 1997 2002 2007 2012 Measles 7 6 150 5 100 4 Cases per 100,000 population 50 3 2 1965 1970 1975 1980 1985 1 1987 1992 1997 2002 2007 2012 Mumps Figure 33.15 Viral diseases and vaccines. 0.7 0.6 0.5 20 Cases per 100,000 population 0.4 10 0.3 0.2 1960 1965 1970 1975 1980 1985 0.1 0.0 1987 1992 1997 2002 2007 2012 Rubella © 2012 Pearson Education, Inc.

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 Figure 33.17 Chicken pox. © 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.

All other infectious diseases Figure 33.18 All other infectious diseases Colds Influenza Figure 33.18 Colds and influenza. 100 200 300 400 Cases per 100 people per year © 2012 Pearson Education, Inc.

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 Figure 33.19 Common cold viruses. © 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.

HA trimer Lipid bilayer M protein NA tetramer RNA NP PA, PB1, PB2 Figure 33.21 HA trimer Lipid bilayer M protein NA tetramer RNA Figure 33.21 Electron micrograph of influenza virus. 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.

Bird virus Reassortant virus Human virus Figure 33.22 Bird virus Reassortant virus Human virus Infection with human virus Infection with bird virus Infection with reassortant virus Figure 33.22 Influenza virus reassortment. Reassortment of human and bird virus © 2012 Pearson Education, Inc.

33.8 Influenza Influenza epidemics and pandemics occur periodically 1957 outbreak of Asian flu 1997 outbreak of avian influenza © 2012 Pearson Education, Inc.

Country of origin Countrywide epidemic Localized outbreaks Figure 33.23 Figure 33.23 An influenza pandemic. Country of origin Countrywide epidemic Localized outbreaks Routes of spread © 2012 Pearson Education, Inc.

33.8 Influenza Prevention Treatment 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 Figure 33.27 Hepatitis B virus (HBV). © 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.

HBV vaccine 1982 HAV vaccine 1995 Cases per 100,000 population Figure 33.26 HBV vaccine 1982 HAV vaccine 1995 20 Hepatitis A Hepatitis B 15 Hepatitis C Cases per 100,000 population 10 5 Figure 33.26 Hepatitis in the United States. 1975 1980 1985 1990 1995 2000 2005 2010 Year © 2012 Pearson Education, Inc.

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.

Syphilis Gonorrhea Figure 33.28 500 World War II Birth control pills 400 300 Reported cases per 100,000 population Gonorrhea 200 100 Penicillin Figure 33.28 Reported cases of gonorrhea and syphilis in the United States. 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 Year © 2012 Pearson Education, Inc.

33.12 Gonorrhea and Syphilis 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 Figure 33.29 The causative agent of gonorrhea, Neisseria gonorrhoeae. © 2012 Pearson Education, Inc.

33.12 Gonorrhea and 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 Figure 33.30 The syphilis spirochete, Treponema pallidum. © 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 Figure 33.32 Cells of Chlamydia trachomatis (arrows) attached to human fallopian tube tissues. © 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 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, AIDS-like 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 Figure 33.37 Kaposi’s sarcoma. © 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.

Mature form Budding particles Figure 33.38 Figure 33.38 Human lymphocyte releasing HIV. Budding particles © 2012 Pearson Education, Inc.

Interaction of HIV with a host cell 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 Figure 33.39 Infection of a CD4 target cell with the AIDS virus, HIV. Nucleus Interaction of HIV with a host cell Fusion of the HIV envelope with the host cell © 2012 Pearson Education, Inc.

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.

Subclinical immune dysfunction Figure 33.40 Symptom- free Swollen lymph glands Subclinical immune dysfunction Oppor- tunistic infections Systemic immune deficiency 1000 900 106 Normal range for T cells 800 700 CD4 T cells per mm3 of blood HIV RNA copies per ml 600 104 500 Significantly depressed T cells 400 300 Death 102 200 Severe T cell depletion Figure 33.40 Decline of CD4 T lymphocytes and progress of HIV infection. 100 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Time (months) after HIV exposure © 2012 Pearson Education, Inc.

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.