BIOL 2320 J.L. Marshall, Ph.D. Chapter 21 – Miscellaneous Bacterial Agents of Disease* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. 21.1 The Spirochetes [I. Spirochetes] Spirochetes are helical, flexible cells with periplasmic flagella (fig. 21.1). Gram negative, the majority of spirochetes are free-living saprobes or commensals of animals and are not primary pathogens. The two most significant exceptions include species belonging to the genera Treponema and Borrelia. See System’s Profile 21.1 Miscellaneous Bacterial Pathogens Treponemes: Members of the Genus Treponema [1. Syphilis] Treponemes are strict parasites with complex growth requirements, must cultivate them in live cells. Syphilis, caused by Treponema pallidum pallidum, is a sexually transmitted disease responsible for venereal and congenital syphilis. Treponema pallidum is a motile spirochete (fig. 21.1a & fig. 21.1b). Motility is the result of periplasmic flagella. Obligate anaerobes with a generation time of 4-18 hours. Pathogenic treponemes cannot be cultivated in vitro. See Pathogen Profile #1 Treponema pallidum (T. pallidum pallidum) Treponema pallidum: The Spirochete of Syphilis The exact origin of syphilis is not clear. What is certain is that it is sexually transmitted and can be found worldwide. Epidemiology and Virulence Factors of Syphilis Humans are the natural host and source of T. pallidum. It is fastidious and can not survive outside the host for very long. Syphilis cases were in decline until the 1990’s, but now there is an increase in the number of cases (See fig. 18.22). Pathogenesis and Host Response T. pallidum binds to epithelial cells by its hooked tip. The ID = 50 – 100 cells. Its outer membrane proteins are part of its infectious process. CLINICAL MANIFESTATIONS Untreated syphilis is marked by clinical stages as primary, secondary, and tertiary. There are multiple signs and symptoms for each stage. Based on these broad descriptions of the signs and symptoms, syphilis can “imitate” many other diseases. See Table 21.1. Syphilis is mostly transmitted during the primary and secondary stages. Primary Syphilis Characterized by an ulcerative lesion (chancre) at the site of infection (fig. 21.2). Infection of other individuals can occur. Lymph nodes in the region of organ / tissue infection become enlarged. The chancre will heal, but the person is still highly infectious. Secondary Syphilis After ~ 6 weeks, the chancre heals and the secondary stage appears. The organism has now invaded many tissues and organs of the body. This stage is characterized by a red – brown rash all over the skin (fig. 21.3). These skin lesions contain viable spirochetes. 1 BIOL 2320 J.L. Marshall, Ph.D. Latency and Tertiary Syphilis Latency can last for 20 years or longer. The final stage, tertiary syphilis, is rare due to use of antibiotics. There can be multiple organ failure at this stage you see ulcers known as gummas (fig. 21.4). Syphilis is divided into 3 stages (Table 21.1), with different signs and symptoms: 1. primary syphilis = chancre at site of infection, first appearing 3 weeks after infection (fig. 21.2). The lesion is accompanied by lymph node enlargement in the region. The chancre heals in 5-10 days on its own. HOWEVER, if untreated... 2. secondary syphilis occurs weeks or months after primary syphilis. Characterized by multiple skin lesions, rashes (fig. 21.3), fever, sore throat, malaise and lymphadenopathy (swelling of the lymph nodes). Lesions can also occur on internal organs at this stage. The lesions contain treponemes and are highly infectious. Antigen-antibody complexes are detectable. If these lodge in kidney glomeruli, kidney damage can result. If they lodge in joints, they can cause arthralgias (pain or gout of the joint). 3. If it is still untreated, years later, tertiary syphilis occurs. Gumma formation, with few if any treponemes (fig. 21.4). Gummas are swollen syphilitic tumors. Cardiovascular diseases, often fatal, occur at this stage when lesions affect aortic valves or cause aortic aneurysms. Final effects include blindness and dementia (insanity). Congenital Syphilis In pregnant women, T. pallidum can cross the placenta and infect the fetus at anytime during the pregnancy where it can multiply in fetal tissue causing congenital syphilis (fig. 21.5). Most commonly, it occurs during the second and third trimesters. The pathogen inhibits fetal development with the possible consequence of spontaneous miscarriage or stillbirth. Infants born with T. pallidum infections have symptoms including nasal discharge, skin eruptions and loss, bone deformation, and nervous system abnormalities. Clinical and Laboratory Diagnosis The stages of syphilis can mimic other diseases. Complications of diagnosing syphilis include the signs and symptoms of each stage can seem unrelated, the chancre and skin rash can imply other bacterial, fungal or parasitic infections. And there can be other STDs such as gonorrhea and chlamydiosis that complicate diagnosis. Special stains using silver can be used to view the cells in bright-field microscopy (fig. 21.6). Patient samples can be tested with DNA probes to determine the presence of the organism. Testing Blood for Syphilis Several antibody tests can be done: RPR, VDRL, and fluorescent antibody tests. Treatment: Penicillin G (So far, there is no penicillin resistance.) Those individuals at most risk should receive regular monitoring. http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm Nonsyphilitic Treponematoses These diseases resemble syphilis, but they are rarely sexually and congenitally transmitted. Bejel Known as nonvenereal childhood syphilis caused by the subspecies T. pallidum endemicum. Seen in people native to Middle East and North Africa. Can be transmitted by direct contact and fomites, enters through breaks in the skin and mucous membranes. The infection starts in the mouth, then moves to the skin and palms (fig. 21.7a). Yaws endemic to warm, humid tropical regions of Africa, Asia, and South America. It caused by the subspecies T. pallidum pertenue. It is spread by direct contact and fomites. Unsanitary and crowded living conditions contribute to the spread. The organism forms a “mother yaw” on the legs (fig. 21.7b). Pinta is a chronic skin infection caused by T. pallidum carateum. Transmission is by several years of close contact, with poor hygiene. Mostly found in isolated regions of Latin America. 2 BIOL 2320 J.L. Marshall, Ph.D. Borrelia: Arthropod-Borne Spirochetes [2. Lyme disease] Borrelia are morphologically distinct from other spirochetes, they tend to be larger. The bacterium has very specific growth requirements. The Borrelia are transmitted by insect vectors lice and ticks. Borrelia burgdorferi and Lyme Disease Lyme disease was recognized in the United States in 1975. An outbreak of arthritis occurred near Lyme, Connecticut. Since then, the disease has increased dramatically. There were over 13,000 cases reported in 1994; by 20057 the number of cases had increased to more than 21,000. The greatest concentration of the disease is in areas where there are high mouse and deer populations. See 21.1 MAKING CONNECTIONS Lyme disease is caused by Borrelia burgdorferi, a spirochete (fig. 21.9). The disease is zoonotic1: it is transmitted by ticks of the genus Ixodes (figure 21.9b). As a larva or nymph of Ixodes feeds on a mouse (i.e., white-footed mouse in the northeastern U.S., and the dusky-footed wood rat in California), where it picks up Borrelia. The nymph is relatively nonspecific and will feed on any type of warm blooded vertebrate, including humans and their pet dogs and cats. The disease is characterized by a bull's eye lesion (fig 21.9c) at the bite location, fever, headache, achy muscles, stiff neck and dizziness. If untreated or treated too late, the disease can progress causing cardiac dysrhythmias and neurological symptoms such as facial palsy. After several weeks or months, a crippling arthritis can attack the joints. Some people develop chronic neurological complications that are severely disabling. Lyme disease acquired during pregnancy may lead to infection of the fetus and possibly stillbirth. Treatment: Early treatment with tetracycline and amoxicillin has been effective. 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases Vibrio cholerae – comma-shaped rods with one flagellum; Campylobacter jejuni – short spirals or curved rods with one flagellum; and Helicobacter pylori – tight spirals and curved rods with several polar flagella. One common feature to all of these is that they are able to survive the harsh intestinal environment. The Biology of Vibrio cholera [1. Vibrio] Cholera is an acute infection by Vibrio cholerae. Vibrio cholerae is G-, motile by polar flagella, curved or comma-shaped rod (fig. 21.10). Oxidase positive, facultative anaerobe. Epidemiology of Cholera El tor biotype is most prevalent worldwide. It can survive longer outside the host. The most recent outbreak was after the 2010 earthquake in Haiti. It ranks at the top in morbidity and mortality world wide, but tends to be rare in the US. If an outbreak does occur, then it is usually near the Gulf of Mexico. The organism enters the human host through contaminated food or water. Infected individuals shed the pathogen into sewage, which contaminates water supplies. Spread of the disease is by the fecal-oral route. Carriers harbor the organism in their gall bladders, just as Typhoid Mary did with typhoid. 1 Zoonotic (or Zoonosis): infections communicated from animals to humans. 3 BIOL 2320 J.L. Marshall, Ph.D. Pathogenesis of Cholera: Toxigenic Diarrhea It is characterized by profuse, watery discharge. Initially diarrhea is brown and then develops to a pale whitish color known as "rice water" because it contains flecks of mucous. It may be accompanied by vomiting. The cells adhere to the microvilli of epithelial cells where they multiply and produce a toxin called cholera toxin (CT).