Sexually Transmitted Diseases Of Bacterial Origin
Gonorrhea is the most frequently reported communicable disease in many of the more developed countries. Rates are 5–50 times higher than in the less developed world. The Gram-negative coccus that causes the disease is called Neisseria gonorrhoeae. It is a highly specialized organism that requires a mucosal surface to gain access to the body. The most important health consequence of gonorrheal infections is fallopian tube damage and the associated predisposi- tion to ectopic (tubal) pregnancies and infertility.
In men, urethritis is the most common clinical manifestation of gonorrhea. Symptoms include dysuria and/or a purulent urethral discharge. Complications of gonorrhea are uncommon in men, but ure- thral stricture, epididymitis and prostatitis can occur. Between 20 and 30% of heterosexual men with symptomatic gonococcal urethritis are simultaneously infected with Chlamydia trachomatis.
Gonococcal infection in women is often asymptomatic. Morbidity associated with the infection, however, is far greater than that seen among infected men. A significant number of women diagnosed with gonorrhea are identified in sexually transmitted disease (STD) clinics as the asymptomatic consort of an infected partner. Uncomplicated urogenital gonococcal infection in women may present as dysuria from urethritis, vaginal discharge from cervicitis, or purulent drainage from the Skene or Bartholin glands at the vaginal introitus. Pelvic inflammatory disease (PID) is a term used to describe infection of the upper genital tract, including endometritis, salpingitis and peritonitis. Neisseria gonorrhoeae and C. trachomatis are the two pathogens most commonly isolated from women with positive cultures for PID. Women with gonococcal PID present with lower abdominal pain, abnormal uterine bleeding, dyspareunia (pain with intercourse) and fever. Although mortality from PID is low, morbidity is extremely high. PID is an important risk factor for chronic pelvic pain, infertility and tubal pregnancies. In some areas of Africa, up to 50% of women are infertile as a result of tubal occlusion from gonococcal PID.
Other serious clinical manifestations include disseminated gonococcal infection (DGI) and gonococcal ophthalmia neonatorum, a severe form of conjunctivitis affecting newborn infants who acquire the infection in the birth canal. Neonatal gonococcal ophthalmia can result in blindness if left untreated. It is a rarity in developed countries because neonatal ocular prophylaxis is mandated at birth, but remains a significant problem in many resource-poor parts of the world.
Gonorrhea is treated with antibiotics. Due to antibiotic resistence profiles, a parenteral cephalosporin plus doxycycline or azithromycin is currently first-line therapy for uncomplicated infections, but the choice of antibiotic evolves with resistence profiles and the propensity for the organism to be associated with other STDs.
Epidemiology of gonorrhea
Gonorrhea is largely a disease of youth. Incidence peaks in men and women at ages 18–24 years. In addition to age, the risk factors include low socioeconomic status, urban residence, unmarried status, non- white race, male homosexuality and prostitution.
Biology of N. gonorrhoeae
Gonococci enter the body by attaching to nonciliated columnar mucosal epithelial cells using specialized surface structures on the bacteria known as pili (Fig. 46.1). Following attachment by the pili, the gono- cocci are endocytosed by the cell. At this stage, a lipopolysaccharide (LPS; endotoxin)-mediated event is activated and nearby cells are killed. Following endocytosis of the bacteria, vacuoles containing viable and replicating gonococci pass through the cell from the mucosal surface to the subepithelial membrane. They are then released into the underlying tissues. The surface damage caused by the gonococcus allows other pathogens, such as chlamydia, to gain access to the upper reproductive tract and cause multiorganism PID. Movement of the gonococci to subepithelial sites also explains frequent failure to document its presence in the fallopian tube despite cervical culture-positive PID.
Gonococci develop their antibiotic resistance through plasmidmediated and chromosomal mechanisms. Most plasmid-mediated resistance is to penicillin and tetracycline. Chromosomally mediated resistance is more general and involves mutations that alter cell wall permeability or the affinity of binding proteins to antibiotics.
There are many similarities between the infections caused by N. gonorrhoeae and Chlamydia trachomatis (CT). Chlamydiae access the body by invading the same epithelial cells of the endocervix, urethra, endometrium, fallopian tubes, rectum and conjunctivae that are host to the gonococcus. Infections in men are relatively asymptomatic and of low morbidity; the major consequence of infection in the male is the risk of transmission to a female partner. In women, gonococcal and chlamydial infections can result in PID, chronic abdominal and pelvic pain, infertility and ectopic pregnancy. There is risk to the newborn infant from a birth canal infected with gonococci or chlamydiae. The greatest clinical difference between female infection with gonococci and CT is that chlamydial PID is often asymptomatic. Hence, chlamydial infection is a major public health hazard because of the potential for undetected serious damage to the upper reproductive tracts of women.
Chlamydia trachomatis is the most common STD in the USA and Europe. Chlamydiae are unique bacteria. Like viruses, they are obligate intracellular parasites and can only be propagated in cell culture. Chlamydia causes about 50% of the cases of nongonococcal urethritis in men. In women, chlamydia can cause mucopurulent cervicitis and the “urethral syndrome.” In the latter, pain on urination is associated with the presence of white blood cells, but no bacteria, in the urine. Unlike gonorrhea, chlamydial infection of the upper genital tract often invades the endometrium and even the fallopian tubes without causing overt signs of PID. Such subclinical infection may first be recognized with diagnosis of the consequent infertility or ectopic pregnancy.
Several strains of chlamydia cause a unique disorder known as lymphogranuloma venereum (LGV), a chronic disease that, like syphilis, has three clinical stages. The primary lesion of LGV is a small, inconspicuous papule of the genitalia that quickly and quietly disappears. The secondary stage of LGV is characterized by fever, malaise and either acute lymphadenitis of the inguinal region (bubo formation = inguinal syndrome) and/or acute hemorrhagic proctitis (anogenitorectal syndrome). Most people recover uneventfully from the second stage. In an unfortunate few, the chlamydiae persist in the anogenital tissues and incite a chronic inflammatory response that can cause genital tract ulcers, fistulae and strictures. LGV is endemic in much of the less developed world but sporadic in the USA and Europe. Neonates exposed to chlamydia in the birth canal may develop afebrile pneumonia or conjunctivitis that can progress to blindness.
Unlike gonococci, chlamydiae require prolonged treatment to eradi- cate the intracellular reservoir of the bacteria. First-line therapy is presently azithromycin or doxycycline. In vitro data and clinical experience indicate that CT may persist within certain infected cells for many years. Because of frequent coexistence of gonorrhea and chlamydial infection, most treatment regimens include antibiotics active against gonococci and chlamydia. True antibiotic resistance is rare in chlamydial infections.
Epidemiology of chlamydial infection
Chlamydia infection is a disease of the young. Additional risk factors include low socioeconomic status, a high number of sexual partners and oral contraceptive use. Barrier methods of contraception (condom, diaphragm, diaphragm plus spermicide) reduce risk.
Biology of chlamydia
The chlamydiae are structurally complex microorganisms. Like viruses, chlamydiae are obligate intracellular parasites. They are classified as bacteria because they contain both DNA and RNA. Like Gram-negative bacteria, they possess outer membrane proteins and an LPS. Chlamydiae differ from all other bacteria in that their growth cycle is characterized by transformation between two distinct forms: the elementary body and the reticulate body (Fig. 46.2). The elementary body is a highly infectious, rigid extracellular growth form that is metabolically inactive. The elementary body attaches to nonciliated columnar or cuboidal epithelial cells and induces ingestion by the host cell. The elementary body-containing phagosome does not fuse with host cell lysosomes, a characteristic crucial to CT survival and unique to only a few organisms (Mycobacterium tuberculosis is another). Within the phagosome, the elementary body reorganizes into a larger, metabolically active, fragile and noninfectious reticulate body. The reticulate bodies divide repeatedly by binary fission within the phagosome of the host cell. They will ultimately reorganize back into infectious elementary bodies that are released when the host cell dies.
There are 15 different serotypes or serovars of chlamydiae. These serovars are identified as A–K, Ba, and L1, L2 and L3. Strains D–K are associated with chlamydial STDs. L1, L2 and L3 cause LGV.