Infections of the Urogenital Tract and STD's
I. The urogenital tract consists of those organs and glands that are involved in production, storage and discharge of urine and those organs involved in reproduction. The organs that are responsible for urine production, storage and discharge are the kidneys, ureters, urinary bladder and urethra. The male reproductive tract shares the urethra with the urinary tract. Other male reproductive organs include the testes, vas deferens, seminal vesicles, penis and bulbourethra. The female reproductive tract is distinct from the urinary tract and consists of the ovaries, ovarian tubes (fallopian tubes), uterus, vagina, clitoris, labia minora and labia majora. For the most part, the internal parts of these tracts are sterile.
A. The flow of urine and mucus through the urinary tract helps to eliminate bacteria that have invaded. The distal urethra is colonized by several bacterial species in both the male and female but bacterial numbers are reduced by the washing action of the urine during urination. The low pH of urine also contributes an antimicrobial affect.
B. The skin of the reproductive organs are colonized by several species of bacteria including members of the genus Streptococcus, Staphylococcus and Micrococcus. The skin of the external female genitalia may also be colonized by the yeast Candida albicans.
C. The vagina is host to several species of bacteria. In the prepubescent and post-menopausal female the species of bacteria are similar to those seen on the skin with some enteric bacteria present. At puberty, hormonal changes lead to increased polysaccharide levels within the vagina (primarily glycogen). Members of the genus Lactobacillus come to be the predominant species in the vagina. Metabolism of carbohydrates by Lactobacillus leads to the production of lactic acid and a subsequent drop in the pH of the vagina to around 4.5. This significant change leads to the elimination of most bacteria and yeast from the vaginal mucosa.
II. Symptoms and signs associated with infection of the urinary tract include purulent discharge from the urethra, pain during urination (dysuria), urge to urinate (even when little urine is present in the bladder), pain in the lower back, fever and chills. In the elderly these symptoms may not be present. Most urinary tract infections (UTI’s) begin with infection and inflammation of the urethra (urethritis). If untreated this infection can ascend into the bladder causing a condition known as cystitis. The infection can continue to ascend causing infection of the kidneys (pyelonephritis). It is possible for infection to begin in the kidneys when bacteria are present in the blood. Though this occurs it is rare. In the male the prostate can become infected (prostatitis). Several behaviors increase the chances of contracting a UTI, these include not urinating frequently enough and not fully emptying the bladder when urinating. This retained urine provides a suitable medium for bacterial growth often containing protein and sugars removed from circulation by the kidneys. Lack of hydration can lead to insufficient urine production, this in turn can lead to the development of a UTI. Finally, in females, improper wiping after urination or defecation can facilitate the transfer of organism from the anus to the distal urethra.
A. Most urinary tract infections in women are due to the enteric bacteria E. coli. Endogenous spread of this organism from the perianal region to the distal urethra is easily accomplished in the female. It was once thought that this type of infection was solely due to poor personal hygiene. Though proper hygiene plays a role in the development of UTI’s, recent investigations indicate that certain strains of E. coli are more capable than others at colonizing the urethra. If a women carries one of these strains she is much more likely to suffer from a UTI than a women who is colonized with a more benign strain of E. coli.
B. Due to the relatively short length of the female urethra spread of this organism to the bladder occurs much more easily in the female. Once in the bladder the pathogen can continue to ascend the urinary tract. Most bladder infections occur in due to such a progression.
C. Urinary tract infections in males are not as frequent due to differences in anatomy as compared to the female. Furthermore, due to the longer urethra, infection of the distal urethra does not progress into cystitis as frequently in the male. When a urinary tract infection does occur in the male, spread to and infection of the accessory sex glands (prostate, bulbourethra, Cowper’s gland, etc.) may occur.
III. Leptospira interrogans is a spirochete that is shed in the urine of many wild and domestic animals (including cats and dogs). This pathogen causes a disease known as leptospirosis. L. interrogans are contracted through the conjunctiva, oral mucosa or abrasions in the skin due to contact with water or soil contaminated with the urine of an infected animal. Once in the body, it is disseminated to several organs but causes disease by affecting the liver, kidneys and central nervous system. Most infections are mild and are limited by the production of antibodies 7-14 days after infection. Before production of antibodies the patient may demonstrate fever. Some strains of this bacteria result in liver damage and infection is accompanied by jaundice. Growth of the organism in the kidney leads to shedding of the bacteria in the urine. Significant reduction in renal function can occur and is the most common cause of death associated with leptospirosis.
IV. Streptococcus pyogenes is the etiologic agent of strep throat and erysipelas. If this condition goes untreated the strong immune response that results can have a detrimental effect on the kidney. This is due to the presence of antigen-antibody complexes on the surface of the cells of the glomerulus. The pathogenesis of this condition is unclear. It may be due to deposition antigen-antibody complexes that were circulating in the blood. More probably it is due to the presence of proteins on the surface of certain strains of S. pyogenes that appear similar to those found on the surface of the cells in the glomerulus of the kidney. Antibodies that will bind these bacterial proteins will also bind to the glomerular cells. In either case, complement is activated and leads to destruction of the glomerulus. In most cases, the damaged renal tissue will heal with no long term reduction in renal function.
V. Coinfection of the vagina with Gardnerella vaginalis and anaerobic bacteria of the genus Bacteroides results in a condition known as nonspecific vaginitis. This infection results in a frothy, fishy-smelling discharge. Transmission to a male during sexual intercourse can lead to the appearance of lesions on the penis. This condition is known as balantitis. This infection only occurs if the pH of the vagina rises above 5. Successful treatment of this condition in the female requires the re-establishment of the normal flora of the vagina so that the normal pH of the vagina (3.5.- 4.5) can be maintained.
VI. Toxic shock syndrome is a rapidly progressing condition which begins with muscle aches, head ache and high fever. It can progress to shock and coma quickly resulting eventually in death. Most cases have been linked to the use of "super" tampons. When super tampons were first released onto the market, they contained certain chemicals that restricted the growth of the normal flora of the vagina. This lack of microbial antagonism allowed S. aureus to proliferate on the mucus membrane or within the tampon itself. Most women who suffer from this disease often have left the tampon in for extended periods of time. This appears to allow the toxins produced by S. aureus to be held in the tampon and slowly absorbed through the mucus membrane. The toxin known as Toxic Shock Syndrome Toxin 1 (TSST-1) is now known to be a super antigen. This type of toxin nonspecifically activates helper T cells with the subsequent release of inflammatory mediators. This results in a systemic loss of vascular tone and a rapid drop in blood pressure.
VII. In the female, one of the most common urogenital infections is the vulvovaginitis caused by the yeast Candida albicans. This organism is found as part of the body’s normal flora. Suppression of the normal flora of the vagina leads to overgrowth of this yeast in the vagina and on the labia. This condition is referred to as canididiasis. Many yeast infections occur after the use of a broad spectrum antibiotic. The antibiotic reduces the Lactobacillus population in the vagina allowing the pH to rise and the amount of glucose available for Candida growth to increase. Due to the fact that Candida is not a bacteria, it is not affected by the antimicrobial. Typically this infection is accompanied by itching and a sweet smelling discharge from the vagina. Diabetics and those with suppressed immunity are more susceptible to this condition.
IX. With the exception of endogenously acquired urinary tract infections and yeast infections, the most common pathogens to affect the urogenital tract are those that are sexually transmitted. Currently there are over 20 known pathogens that are sexually transmitted and the Center for Disease Control estimates that 15 million cases of sexually transmitted disease occur annually. Women carry a disproportionate burden of this epidemic. Many of these pathogens cause little or no initial pathology in the female so as to go undetected. Often this leads to spread of the pathogen to other sites in the reproductive tract where they cause considerable disfunction.
A. Neisseria gonorrhoeae invades mucus membranes via attachment by the pili. The resulting inflammatory response results in the ingestion of Neisseria gonorrhoeae by neutrophils and macrophages. The capsule of these organisms allows them to survive within the phagocytic cells. Because the bacteria is very susceptible to drying and oxygen transmission sexual transmission is the most efficient means of transfer.
1. In most cases, Neisseria gonorrhoeae invades the mucus membrane lining the reproductive tracts of men or women.
a. In males the resulting inflammation is painfully obvious. Furthermore, these organism are pyogenic and as such pus will often be discharged from the urethra. If ignored infection can spread into as far as the epididymis. Scarring can block the vas deferens or spermatic ducts resulting in sterility.
b. In females Neisseria gonorrhoeae colonizes the vagina at or near the cervix. Pain, inflammation and a bloody discharge may occur. Often no symptoms are noticed and the infections spreads into the uterus and fallopian tubes resulting in a condition known as salpingitis. This is one etiologic agent of pelvic inflammatory disease (PID). If unattended to PID can result in scarring of the fallopian tubes which can render the female sterile. Neisseria gonorrhoeae can also spread into the blood stream were it colonizes the joints resulting in inflammation and septic arthritis.
c. Spread of Neisseria gonorrhoeae to the mucus membranes of the pharynx and rectum can result from oral or anal sex with an infected person. Presence of rectal gonorrhea in the female is often due to normal spread (due to the proximity of the vagina and rectum).
2. Infection of the fetus as it passes through an infected vagina can result colonization of the eyes (gonococcal ophthalmi neonatorum) leading to blindness. Thus prophylactic administration of antimicrobial eye drops to the eyes occurs routinely immediately after birth. Since spread of Neisseria gonorrhoeae is almost solely due to sexual contact children (other than newborns) presenting with Neisseria gonorrhoeae infections are often reported to child welfare as probable victims of child abuse.
3. Once the drug of choice for Neisseria gonorrhea was penicillin but due to the rapid evolution of strains of penicillinase producing Neisseria gonorrhoeae (PPNG), most cases of this disease are treated with cephalosporins. These antimicrobials act in much the same way as penicillin but are different enough in chemical structure not to be degraded by the same enzymes that effect penicillin.
4. In most states extensive measures were put in place during and after World War II to detect and eliminate gonorrhea. These included widespread distribution of condoms within the military, use of penicillin and notification of sexual contacts (if known) to identify and treat those who were infected. These measures drove the rate of gonorrhea to all time lows in the 1950’s. This trend was reversed during the 60’s due mainly to increased the birth control pill ( consequently there was reduced reliance on condoms for birth control). Increased rates of sexual activity and the nature of the activity (multiple partners in short periods of time) led to increases in the occurrence of gonorrhea. During the mid-80’s) with increased awareness of HIV, condom use increased and some surveys indicate that dangerous types of sexual activity decreased. Consequently decreased levels of Neisseria gonorrhoeae infection have been observed. It is obvious, but needs to be stated, that patients with Neisseria gonorrhoeae infections are often practicing those behaviors that lead to numerous other sexually transmitted diseases. Many of these diseases are more life threatening and less treatable than gonorrhea.
B. The causative agent of syphilis is a spirochete known as Treponema pallidum. This organism survives for only a short time outside a human host. Thus spread of the organism involves intimate contact between an infected person and a susceptible person.
1. Initially infection with Treponema pallidum results in an open sore known as a chancre. This is referred to as primary syphilis. Though chancres appear painful, these sores often inflict little or no pain. In the male they are on the external genitalia and often are immediately noticed. In the female they can be within the vagina and completely escape notice. The person is infectious due to the presence of bacteria in the exudate from the sores. These lesions will resolve in a few weeks. The organism is still present in the blood.
2. Secondary syphilis develops as the organism spreads from the site of initial infection throughout the body. Multiple eruptions on the skin and mucous membrane, fever, headache, sore throat and a brownish rash may be observed or reported. Multiple occurrences of this type of condition is possible. If untreated these reoccurences will also cease.
3. Tertiary syphilis develops many years after initial exposure. This stage involves the development of gummas which are rubbery masses of tissue that develop on any organ which was infected during the secondary phase of infection. Though not fatal in themselves, gummas can interfere with normal functioning of the organ. During this phase neurological involvement may occur. This neurosyphilis can lead to loss of sight, disruption of motor control, convulsions and mental derangement.
C. Haemophilus ducreyi is the etiologic agent of chancroid. This organism is spread through sexual contact or by other direct contact between infected surfaces. Infection results in lesions that resemble a syphilitic chancre. Lesions are usually found on the genitals. Unlike syphilitic chancres, which are generally painless, the lesions caused by H. ducreyi are painful. Usually extreme swelling of lymph nodes in the inguinal area occurs. This can lead to the rupture of these nodes. Though not common in this country, this disease is endemic in many areas of the world. This infection seems to be more common in uncircumcised males. In Africa the region in which this condition is endemic coincides with the region where AIDS is epidemic.
D. Chlamydia are unique bacteria. They have an inner and outer membrane and are categorized as gram negative organisms. Yet, they do not engage in metabolic activity or binary fission unless they have invaded a eukaryotic cell. Thus, members of the genus Chlamydia are all considered obligate intracellular parasites. These organisms lack the mechanisms to make ATP and thus are unable to survive without a host cell providing them with energy. They have an unusual dimorphic life cycle and infect through a metabolically inactive spore-like form. The life cycle of a Chlamydia includes a small, infectious spore (elementary body) which can survive outside the cell and a larger, metabolically active cell (reticulate body) which is found only within a host cell. The infectious elementary body enters macrophages and neutrophils by way of phagocytosis. They convert into the reticulate body within the phagocytic vacuole and begin to grow. The action of lysosomes do not destroy the reticulate body. During the course of growth, more elementary bodies are formed and remain within the vacuole. When the phagocytic cell dies, these elementary bodies are released and ingested by other phagocytes thus continuing the lifecycle. Clinically in the United States, chlamydia have significant impact as the most common sexually transmitted disease agent.
1. Chlamydia trachomatis is transmitted person to person. There are many subspecies of C. trachomatis which are referred to as serovars. Minor differences in serovars leads to clinically different infections. Depending on the serovar this transmission may be from simple contact or via fomites or may require sexual contact. Three distinct diseases are observed to be caused by members of this species. Infection of the eye was discussed previously.
a. Certain serovars infect the urogenital tract. Transmission of these organisms relies upon sexual contact. In most cases infection is asymptomatic. In some individuals this infection can progress into urethritis, cervicitis PID and salpingitis. It is estimated that 4 million sexually active individuals become infected annually. Thus if only 10% of those infected progress from an asymptomatic condition to the more serious forms of disease significant morbidity will occur.
i. It is known that transmission of Chlamydia transplacentally and to the neonate during delivery occurs. The significance of this transmission is still under investigation. It has been determined that expectant mothers who carrying Chlamydia trachomatis have dramatically increased rates of stillborn infants and infants who suffer neonatal death.
ii. The neonate who is infected during childbirth may develop a conjunctivitis. The possibility of this occurring is reduced if antibiotic treatment of the eyes occurs immediately after birth.
b. Certain sexually transmitted serovars of Chlamydia trachomatis result in a condition known as lymphogranuloma venereum (LGV). This condition begins with ulceration of the skin and mucosa of the genital organs. It is carried into the lymph nodes by the phagocytes. Swelling of the lymph node results in the formation of a bubo. the node may rupture, drain and then be permanently scarred. Rupture of the lymph node results in fever and nausea along with localized pain. The rupture lymph node can present a site of permanent blockage of the lymphatic vessel.
E. Mycoplasma hominis and Ureaplasma urealyticum are mycoplasmas that colonize the urogenital tract of humans and can exist as part of a persons normal flora with little or no harm to that person. But in some cases U. urealyticum can causes a urethritis and lead to sterility or reduced fertility in both the male and female. M. hominis can cause PID and is implicated in postpartum fever. For the most part it appears that these organisms are spread by sexual contact.
1. In pregnant women these organisms can result in bigger problems. Ureaplasma urealyticum and Mycoplasma hominis have been isolated from amniotic fluid (in the presence of intact fetal membranes) as early as 16-20 weeks gestation. U. urealyticum can cause a chronic, clinically silent chorioamnionitis and premature birth. U. urealyticum and M. hominis are a cause of chronic central nervous system infection in infants. U. urealyticum colonization of the lower respiratory tract is associated with death and development of chronic lung disease in very low birth weight infants.
2. Mycoplasmas lack a cell wall. Consequently antimicrobial drugs that interfere with the synthesis of peptidoglycan have no effect on these organisms. Treatment usually involves tetracycline, macrolides or aminoglycosides.
F. Herpes simplex virus is the causative agent of several recurrent ulcerative diseases. Herpes simplex virus Type 1 (HSV-1) usually infects the mucus membrane of the lips, cheeks, throat or gums. The initial infection results in the formation of vesicles which usually resolve unnoticed but can rupture and ulcerate. The virus spreads into the sensory neurons that enervate these regions. The viral DNA moves through the neuron’s cytoplasm to the nucleus which is located in the trigeminal ganglia. It establishes a latent infection within these neurons. The viral particles can be shed from these neurons at any time after the establishment of latency. Usually this shedding is follows periods of physical or emotion stress. The newly shed particles are released in the same area as the initial viral infection. They result in lesions that rapidly ulcerate. During this period the person is highly infectious. Herpes simplex virus Type 2 (HSV-2) is most commonly associated with genital herpes. It causes ulcerative lesions on the skin of the penis and surrounding regions. In the female the lesions can be on the labia majora or minora or on the mucus membrane of the vagina. Lesions in the vagina may not be accompanied by significant discomfort and may go unnoticed by the women.
1. HSV-1 can be initially infect mucus membranes surrounding the eye (conjunctiva) and thus be maintained in sensory nerves of the eye. Repeated episodes of HSV release can lead to the scarring of the cornea and the loss of vision. This is referred to as herpatic keratoconjunctivitis.
2. Transmission of HSV-1 usually occurs by fomites (shared eating utensils, drinking out of the same glass, etc.) or direct oral contact like kissing. It is a fairly widespread virus in the general public and causes little mortality. Transmission of HSV 2 usually is by sexual contact. Because the lesions in the male are often near the base of the penis condoms may not be effective in limiting the spread of infectious fluids during sexual intercourse. It should also be noted that HSV-2 can be transmitted to the mouth during oral sex.
3. Diagnosis is usually made examination of lesions and history of recurrence. Virus can be easily grown in cell culture and the subtype identified by monoclonal antibodies.
4. Duration of the secondary lesion of both HSV-1 and -2 can be significantly reduced by the use of nucleotide analog drugs. One of the most commonly used is acyclovir.
G. Hepatitis refers to any condition in which the liver becomes inflamed. This may be the result of toxic ingestion, bacterial infection or other less well defined etiologies. Viral hepatitis results from the invasion of liver cells by viruses and the resulting cytopathology. Currently several viruses are known to infect the liver causing viral hepatitis. They are referred to as hepatitis A, hepatitis B, hepatitis C, hepatitis D (delta agent), hepatitis E and hepatitis G. There are probably several other viral agents that are currently circulating that have yet to be isolated and characterized. To date, Hepatitis B and D have been shown to be effectively transmitted via sexual contact. Sexual transmission of Hepatitis C virus is matter of some debate with most evidence indicating that transmission via this route is relatively rare if it occurs at all.
1. Hepatitis B virus (HBV) results in a condition referred to as serum hepatitis. The virus is a enveloped DNA virus. Initial infection leads to severe liver destruction and thus jaundice. Fever and malaise are also common. 5-10% of those infected will become chronically shedders of the virus. The virus is shed into the blood stream and can be found in proteinaceous secretions such as semen. In this country venereal transmission is the most significant route of infection. Transmission can also occur via contaminated blood products and sharing of needles in IV drug use.
a. The chronic shedder releases large amounts of viral protein that make up the outer capsid of the virion (HBsAg). Most of these proteins form a structure that lacks any viral DNA and thus are not infectious. They arrange themselves into small balls or worm-like filaments.
b. Mortality is around 1/100 infected. It is becoming apparent though that persistent infection leads to cirrhosis and probably plays a role in the development of liver cancer. This long term morbidity will reduce the life span of the chronically infected individual significantly.
c. In this country, those measures that reduce the spread of other venereal diseases will serve to reduce the spread of HBV. The development of a safe vaccine has allowed the protection of those exposed to blood and other body fluids. This vaccine is one of the first widely used genetically engineered vaccines.
2. Hepatitis D virus (delta agent; HDV) is a defective virus in that it can not make viral particles without the surface protein of HBV (HBsAg). This virus coinfects cells already harboring Hepatitis B virus. When a person chronically infected with HBV is exposed to the delta agent it may cause the hepatitis to reactive and worsen. Coinfection often results in rapid degeneration of the liver and increased morbidity.
3. Human Papilloma viruses (HPV) are the viruses that are responsible for common skin warts and certain strains of HPV are responsible for genital warts (condylomata acuminata). HPV is usually transmitted by direct contact including sexual contact. The appearance of the warts may take from l to 20 months from the time of exposure but usually become apparent within 4 months. There are over 100 viruses known in the HPV family of viruses. Every year, about 5.5 million Americans are newly infected with genital HPVs — 20 million women and men are now infected.
a. Genital warts are often first noticed as a firm painless tissue on the vulva, penis or area around the rectum. These warts are flesh-colored, lumps which may be single or in groups. They may look like a tiny cauliflower or be flat. HPV can cause warts in the around the mouth due to sexual transmission during oral sex.
b. There is no easy way to tell if someone is infected with an HPV. Asymptomatically infected individuals are capable of HPV transmission. Though condoms do reduce the risk of infection by reducing the amount of direct contact between the genitals during sex, condoms do not entirely eliminate such contact and thus do not totally prevent transmission of HPV.
c. Certain types of HPV can cause abnormal cell growth known as dysplasia. Dysplasia can develop into several kinds of cancer. These include cancers of the penis and anus, and cervical cancer in women. Some types of HPV are referred to as "low-risk" viruses because they rarely develop into cancer; these include HPV-6 and HPV-11. HPV viruses that can lead to the development of cancer are referred to as "cancer-associated types." Sexually-transmitted, cancer-associated HPV have been linked with cancer in both men and women; most importantly they include HPV-16, HPV-18, HPV-31, and HPV-45. These cancer-associated types of HPV cause growths that usually appear flat and are nearly invisible, as compared with the warts caused by HPV-6 and HPV-11.
i. Dysplasia can be detected by Pap smears. They are usually used to check a woman's cervix, but can also be used to check the anus in men and women. A swab is rubbed on the area being checked. The swab picks up some cells, which are smeared on a glass slide and examined under a microscope. If the Pap smear results are not clear, an HPV test can indicate who needs treatment.
ii. If left untreated, genital warts may go away on their own, stay the same or continue to grow. However, most health care providers recommend that they be treated. Warts can be burned off with chemicals, electric current, laser therapy, surgically removed or frozen off. Even after treatment, warts can recur. Sexual contacts need to be identified and similar treated. In some cases, the body will develop an immunity to the particular strain of HPV and eliminates it. However, this immunity may not extend to other strains of HPV
Here are some links!!
Here are two pages hosted by Cornell University Medical Center that give in-depth analysis of pathology affecting the Urogenital tract.
FEMALE GENITAL TRACT http://edcenter.med.cornell.edu/CUMC_PathNotes/Female_Genital_Tract/FGT_2.html
LIVER, GALL BLADDER, & PANCREAS
http://edcenter.med.cornell.edu/CUMC_PathNotes/Liver,GB,Pancreas/Liver,GB,Pancreas.html
Textbook of Microbiology Microbiology of the Genitourinary System
American Social Health Association Introduction to STD's