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Urologia 2014 ; 81 ( 4): 200-208 DOI: 10.5301/uro.5000101

FOCUS ON

ISSN 0391-5603

Sexually transmitted diseases: epidemiological and clinical aspects in adults Salvatore Siracusano1, Tommaso Silvestri1, Daniela Casotto2 1 2

Department of Urology, Trieste University, Trieste - Italy Department of Clinical Pathology, Cattinara Hospital Trieste, Trieste - Italy

Abstract Sexually transmitted diseases (STDs) are the first 10 causes of unpleased diseases in young adult women in the world. The concept of STDs includes a series of syndromes caused by pathogens that can be acquired by sexual intercourse or sexual activity. Adolescents and young adults are responsible for only 25% of the sexually active population and they represent almost 50% of all newly acquired STDs. In this way, we evaluated the epidemiological and clinical aspects of most relevant pathogens as Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Haemophilus Ducreyi, Trichomonas vaginalis, herpes simplex virus, human papilloma virus (HPV) with the exception of hepatitis, and HIV infections for which we suggest specific guidelines. To attain this objective, we analyzed the results of epidemiological and clinical aspects of STDs through a review of the literature using MEDLINE and PubMed database for original articles published using the terms “sexual transmitted disease, epidemiology, diagnosis and therapy” from 2005 to 2014. Keywords: Diagnosis, Epidemiology, Sexually transmitted disease, Therapy

Introduction

Epidemiological aspects

Sexually transmitted diseases (STDs) are one of the most serious public health problems in the world. The term of STDs is used for referencing to a variety of clinical syndromes caused by pathogens that can be acquired and transmitted through sexual activity. In this context, we have tried to review the most relevant epidemiological and clinical aspects that characterize this group of diseases for which pathogens are shown in Table I. In this overview, we report the results of epidemiological and clinical aspects of STDs through a review of the literature using MEDLINE and PubMed database for original articles published using the terms “sexual transmitted disease, epidemiology, diagnosis, and therapy” from 2005 to 2014. Most relevant current publications and data were evaluated with the exception of hepatitis and HIV infections for which specific guidelines should be read.

STDs are among the first 10 causes of unpleased diseases in young adult males and the second major cause of unpleasant diseases in young adult women in the world. Adolescents and young adults are responsible for only 25% of the sexually active population and they represent almost 50% of all newly acquired STDs. Therefore, STDs are epidemic and present important economic consequences (1). Information regarding incidence and prevalence of STDs are heterogeneous. The prevalence of Chlamydia trachomatis infection in young females in 1997 and 2005 was 12.2% and 15.4%, respectively, and 15.7% and 20.5% for young males, respectively. However, the incidence of gonorrhea has decreased by 1% in the same period of time. Syphilis data for men and women show statistical differences, as the incidence of infection was 3.8 cases per 100,000 men in 2002 and 5.1 cases per 100,000 in 2005. In particular, there were 1.1 cases per 100,000 women in 2002 and 0.9 cases per 100,000 women in 2005. However, these data cannot truly reflect the prevalence of this disease because, unlike for other STDs, screening studies are not currently being carried out. In fact, it is estimated that reported cases of STDs represent only 50-80% of reportable STDs. In this context, there are well known risk factors associated with the acquisition of STDs such as biological and behavioral factors, cultural influences, lack of information about transmission of STD, difficulty in accessing prevention services, and lack of number of sexual partners. High-risk sexual behavior often leads to teenage pregnancy and HIV/AIDS infections. This behavior could occur because

Accepted: October 30, 2014 Published online: December 10, 2014 Corresponding author: Salvatore Siracusano Department of Urology Trieste University Cattinara Hospital Via Strada di Fiume 447 34100 Trieste, Italy [email protected]

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TABLE I - Etiologic agents and related disease or syndrome Etiologic agent

Disease or syndrome

Bacteria Neisseria gonorrhoeae

Urethritis, epididymitis, proctitis, vaginitis, cervicitis, bartholinitis

Chlamydia trachomatis

Urethritis, epididymitis, conjunctivitis, lymphogranuloma venereum

Mycoplasma hominis

Salpingitis, urethritis

Ureaplasma urealyticum

Urethritis

Treponema pallidum

Syphilis

Haemophilus ducreyi

Chancroid

Calymmatobacterium granulomatis

Inguinal granuloma (donovanosis)

Virus Herpes simplex (HSV)

Genital herpes, cervical and vulvar cancer

Virus hepatitis A, B, C

Acute hepatitis, chronic hepatocellular carcinoma

Human Papillomavirus (HPV)

Condyloma acuminatum, cervical, vulvar and penile cancer

HIV

AIDS

Protozoa Trichomonas vaginalis

Vaginitis, urethritis

Entamoeba histolytica

Enteritis

Mycetes Candida albicans

Vaginitis, balanoposthitis

Metazoa Phthirus pubis

Lice infestations

Sarcoptes scabiei

Genital Scabies

people do not have sufficient information about transmission of STDs or because they ignore the precautions for a safe sex. In this way, approximately 60% of new HIV infections occur in young people and especially in travelers. Finally, another important issue is related to the role of male circumcision because it is associated with a lower risk of STDs as well as HIV transmission (2-4) as reported in 1855 by Hutchinson who described the indication of this surgical intervention as a probable protection against STDs.

Clinical considerations We report here the most relevant disease from the clinical and epidemiological point of view. Gonorrhea It is caused by a gram-negative diplococcus the Neisseria gonorrhoeae. The incubation period ranges from 3 to 14 days. Risk of infection after one exposure is 10% in men and 40% in women. Men will usually experience lower urinary tract symptoms (LUTS) attributed to urethritis, epididymitis, proctitis, or prostatitis with associated mucopurulent urethral ­discharge. Women may have symptoms of vaginal and pelvic discomfort, © 2014 Wichtig Publishing

dysuria, or abnormal vaginal discharge, but are most often asymptomatic. Both symptomatic and asymptomatic infections can lead to pelvic inflammatory disease (PID) and its subsequent complications. Therefore, screening in all sexually active adolescents and women up the age of 25 should be ­performed yearly as well as any women with risk factors such as a new sexual partner or multiple sexual partners. Evidence of gonococcal dissemination are rare today and include arthritis, dermatitis, meningitis, and endocarditis. A gram stain of a male urethral specimen that dem­ onstrates polymorphonuclear leukocytes with intracellular gram-negative diplococci can be considered diagnostic for infection with Neisserie gonorrhoeae in symptomatic men. However, because of lower sensitivity, a negative gram stain should not be considered sufficient for ruling out infection in asymptom­atic men. In addition, gram stain of endocervical specimens, pharyngeal, or rectal specimens is not sufficient to detect infection, and therefore are not recommended. Specific testing for Neisserie gonorrhoeae is recommended, thanks to increased utility and availability of highly sensitive and specific test­ing methods and because a specific diagnosis might enhance partner notification. Specific diagnosis of infection with Neisserie gonorrhoeae can be performed by testing endocervical, vaginal, urethral (men only), or urine

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specimens. Culture, nucleic acid hybridization tests, and nucleic acid amplification tests (NAATs) are available for the detection of genitourinary infection with Neisserie gonorrhoeae (5). Culture and nucleic acid hybridization tests require female endocervical or male urethral swab specimens. NAATs allow testing of the widest variety of specimen types, including endocervical swabs, vaginal swabs, urethral swabs (men), and urine (from both men and women), and they are U.S. Foods and Drugs Administration (FDA)-cleared for use. The sensitivity of NAATs for the detection of Neisserie gonorrhoeae in genital and nongenital anatomic sites is superior to culture but varies by NAAT type (5-9). In relation to therapy, it is suggestible to refer to STDs treatment guidelines 2010 (10), which provide as follows: (1) Ceftriaxone 250 mg in a single intramuscular dose with Azithromycin 1 g orally in a single dose (2) or doxycycline 100 mg orally twice daily for 7 days, or alternatively Cefixime 400 mg in a single oral dose with Azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice daily for 7 days Chlamydia trachomatis It is a gram-negative intracellular parasite belonging to the family Chlamydia. It is prevalent in sexually active adolescents and young adults. The majority of both men and women are asymptomatic. Approximately 50% of men experience LUTS due to urethritis, epididymitis, or prostatitis and may notice clear or white urethral discharge. This parasite is the most common cause of epididymitis in young men. Seventy-five per cent of women who become infected are asymptomatic, while 40% of them will develop PID (11). Scarring of the fallopian tubes from this pathological agent puts patients at risk for recurrent PID with vaginal flora, ectopic pregnancy, pelvic pain, and infertility. Chlamydia may also be transmitted to newborns during vaginal birth through the exposure of the mother’s infected cervix. In this way, selective screening has been shown to reduce the incidence of PID and women should be screened annually until age 25 or if risk factors such as a new sexual partner are present (12). This infection in women can be diagnosed by testing urine or by collecting swab specimens from the endocervix or vagina. Diagnosis of Chlamydia trachomatis urethral infection in men can be made by testing a urethral swab or urine specimen. Rectal infections in persons who engage in receptive anal intercourse can be diagnosed by testing a rectal swab specimen. NAATs, cell culture, direct immunofluorescence, and nucleic acid hybridization tests are available for the detection of Chlamydia trachomatis on endocervical specimens and urethral swab specimens from men (5). NAATs are the most sensitive tests for these specimens and are FDA-cleared to use with urine. Chlamydia treatment should be provided promptly to all per­sons testing positive for infection because delays in receiving chlamydia treatment have been associated with complications as PID in a limited proportion of chlamydia-infected subjects (13). In this context, it is important to remember that patients infected with gonorrea are often coinfected with

Chlamydia trachomatis, and for this reason, it has been recommended that patients should undergo simultaneous dual treatment that provides, as in case of single chlamydia infection as follows. Azithromycin 1 g orally in a single dose or Doxycycline 100 mg orally twice a day for 7 days. Alternatively, it also suggested Erythromycin 500 mg orally four times a day for 7 days or Levofloxacin 500 mg orally once daily for 7 days. In this context, we describe the Lymphogranuloma venereum that is caused by Chlamydia trachomatis types L1, L2, and L3, and it is extremely rare. The initial manifestation of infection is usually a single, painless ulcer on the penis, anus, or vulvovaginal area that goes unobserved. Patients usually present with painful unilateral suppurative inguinal adenopathy and constitutional symptoms that occur 2-6 weeks after resolution of the ulcer. The diagnosis is based on clinical suspicion, epidemiologic information, and the exclusion of other etiologies for proctocolitis, inguinal lymphadenopathy, or genital or rectal ulcers. Cultures are positive in only 30-50% of cases and Chlamydia trachomatis testing should also be conducted. Genital and lymph node specimens can be tested for Chlamydia trachomatis by culture, direct immunofluorescence, or nucleic acid detection. Treatment cures infection and prevents ongoing tissue damage, although tissue reaction to the infection can result in scarring. Buboes might require aspiration through intact skin or incision and drainage to prevent the formation of inguinal/femoral ulcerations. In relation to therapy, it is advisable to refer to STDs treatment guidelines 2010 (10), which provide as follows: Doxycycline 100 mg orally twice a day for 21 days or alternatively Erythromycin base 500 mg orally four times a day for 21 days. Syphilis It is caused by the spirochete Treponema pallidum. Usually, incubation periods range between 10 and 90 days. The transmission occurs through contact with infectious lesions or body fluids, but it may be also acquired in utero and through blood transfusion. The primary syphilis is characterized by a single painless and indurated ulcer that occurs at the site of inoculation that appears about 3 weeks after inoculation and persists for 4-6 weeks. The ulcer is usually located on the glans or perianal area on the men and on the labial or anal area on women. It is often associated with bilateral, nontender inguinal, or regional lymphadenopathy, and in this way, the ulcer and adenopathy are painless and heal without therapy. Latent syphilis is defined as seroreactivity with no clinical evidence of disease. Secondary syphilis usually begins 4-10 weeks after the appearance of the ulcer but may present as long as 24 months following the initial infection. Secondary syphilis manifests with mucocutaneous and parenchymal signs and symptoms. Frequent early manifestations consist of maculopapular rash on the trunk and arms and generalized nontender lymphadenopathy. After several weeks, a papular rash may accompany the primariy rash. These papular lesions are associated with endarteritis and may therefore become necrotic and pustular. The © 2014 Wichtig Publishing

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distribution commonly affects the palms and soles. In the intertriginous areas, these lesions may enlarge and erode to produce condyloma, which are particularly infectious. Less common manifestations of secondary syphilis include hepatitis and glomerulonephritis. Approximately one-third of untreated patients will develop tertiary syphilis, but it is very rare in industrialized countries except for occasional cases reported in HIV patients. This disease is systemic and can affect almost any organ or system, especially the cardiovascular, skeletal and central nervous system (CNS), and skin. Finally, arthritis, meningitis, uveitis, optic neuritis, general paresis, tabe dorsalis, and gummas of the skin and skeleton are the sequalae associated with tertiary syphilis. Dark-field optical microscope and tests to detect Treponema pallidum in lesion exudate or tissue are the methods for diagnos­ing early syphilis (5). Although no Treponema pallidum detection tests are commercially available, some laboratories provide locally developed PCR tests for the detection of Treponema pallidum. A presumptive diagnosis of syphilis is possible with the use of two types of serologic tests: nontreponemal tests such as Veneral Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR); and treponemal tests [fluorescent treponemal antibody absorbed (FTA-ABS) tests, the Treponema pallidum passive particle agglutination (TP-PA) assay, various Enzyme Immuno Assay (EIAs), and chemilumines­cence immunoassays]. The use of only one type of serologic test is insufficient for diagnosis, because each type of test has limitations, including the possibility of false-positive test results in persons without syphilis. False-positive non-treponemal test results can be associated with various medical conditions unrelated to syphilis, including autoimmune conditions, older age, and injection-drug use (14, 15); therefore, persons with a reactive non-treponemal test should receive a treponemal test to confirm the diagnosis of syphilis. Non-treponemal test antibody titers may correlate with disease activity, and results should be reported quantitatively. However, in some persons, non-treponemal antibodies can persist for a long period of time. Clinical signs of neurosyphilis (i.e., cranial nerve dys­ function, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities) warrant further investigation and treatment for neurosyphilis. Laboratory testing is helpful in supporting the diagnosis of neurosyphilis; however, no single test can be used to diagnose neurosyphilis in all instances. Cerebrospinal fluid (CSF) laboratory abnormalities are common in persons with early syphilis. The VDRL in CSF (CSF-VDRL), which is highly specific but insensitive, is the standard serologic test for CSF. In relation to therapy, it is suggestible to refer to STDs treatment guidelines 2010 (10), which provide as follows: (a) (b)

In case of primary and secondary syphilis: Benzathine penicillin G 2.4 million units IM in a single dose In case of early latent syphilis: Benzathine penicillin G 2.4 million units IM in a single dose (c) In case of late latent syphilis or latent syphilis of unknown duration: © 2014 Wichtig Publishing

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Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1-week intervals (d) In case of tertiary syphilis: Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1-week intervals. Chancroid It is caused by gram-negative bacillus Haemophilus ducreyi. It is the most common sexual transmitted infection (STI) worldwide. It affects men three times more often than women. The incubation period ranges from 1 to 21 days. It causes a painful, non-indurated ulcer on the penis or vulvovaginal area. The ulcer has a friable base covered with a grey or yellow purulent exudate and a shaggy border. It can spread laterally by apposition to inner thighs and buttocks, especially in women. It is associated with inguinal adenopathy that is typically unilateral and tender, with a tendency to become suppurative and fistulize. Haemophilus ducreyi is fastidious and difficult to culture. The special culture media is not widely available and sensitivity of culture remains under 80%. Gram-stain of a specimen obtained from the undermined edge of the ulcer may be more helpful in identifying the short, fine, gram-negative streptobacilli, which are usually arranged in short, parallel chains. Recently, polymerase chain reaction (PCR) assays have been shown to Haemophilus ducreyi. Although no PCR test is currently FDA-approved, testing can be performed by commercial agencies. Approximately 10% of persons who have chancroid are coinfected with Treponema pallidum or HSV (16). HIV and syphilis screening should be performed at the time of diagnosis and 3 months after treatment, if initially negative. Four criteria should be considered in formulating the diagnosis of chancroid: presence of one or more painful ulcers, presence of regional lymphadenopathy, a negative Treponema pallidum evaluation or negative serology at least 7 days after the onset of symptoms, and negative HSV culture from the ulcer exudates (17). In relation to therapy, it is advisable to refer to STDs treatment guidelines 2010 (10), which provide as follows: Azithromycin 1 g orally in a single dose or alternatively Ceftriaxone 250 mg intramuscularly (IM) in a single dose or alternatively Ciprofloxacin 500 mg orally twice a day for 3 days Trichomonas vaginalis It is caused by the flagellated protozian Trichomonas vaginalis, which can inhabit the vagina, urethra, Bartholian glands, Skene’s glands, and prostate. It cannot infect the rectum or mouth. The human being is its only known host. The incubation period ranges from 4 to 28 days. Trichomonasis is one of the most common STDs, with approximately 174 million new cases reported worldwide each year.

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Trichomoniasis is typically asymptomatic in men but may produce short-lived symptoms of urethral discharge, dysuria, and urinary urgency. Clinical manifestations in women include the sudden onset of a frothy white or green, foul smelling vaginal discharge, pruritis, and erythema. Other symptoms include dyspareunia, suprapubic discomfort, and urinary urgency. It has been associated with premature labor in pregnant women and with an increased risk of HIV transmission (18, 19). Clinical examination may reveal a frothy discharge and the characteristic “strawberry vulva” or “strawberry cervix.” Diagnosis of vaginal trichomoniasis is usually performed by microscopy of vaginal secretions, but this method has a sensitivity of only approximately 60-70% and requires immediate evaluation of wet preparation slide for optimal results. FDA-cleared tests for trichomoniasis in women include OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, Massachusetts), an immunochromatographic capillary flow dipstick technology, and the Affirm VP III (Becton Dickenson, San Jose, California), a nucleic acid probe test that evaluates for Trichomonas vaginalis, Gardnerella vaginalis, and Candida albicans. Each of these tests, which are performed on vaginal secretions, has a sensitivity of more than 83% and a specificity of more than 97%. Both tests are considered point-of-care diagnostics. The results of the OSOM Trichomonas Rapid Test are available in approxi­mately 10 min, whereas results of the Affirm VP III are available within 45 min. Although these tests tend to be more sensitive than those requiring vaginal wet preparation, false positives might occur, especially in populations with a low prevalence of disease. Culture is another sensitive and highly specific commer­ cially available method of diagnosis. In men, wet preparation is not a sensitive test, and no approved point-of-care tests are available. Culture testing of urethral swab, urine, or semen is one diagnostic option; however, NAATs [i.e., PCR or transcription-mediated ampli­fication (TMA)] have superior sensitivity for Trichomonas vaginalis diagnosis in men (20-23). In relation to therapy, it is suggestible to refer to STDs treatment guidelines 2010 (10), which provide as follows: Metronidazole 2 g orally in a single dose or alternatively Tinidazole 2 g orally in a single dose Herpes simplex virus Genital herpes is an infection that afflicts more than 50 million people in the United States. It is caused by herpes virus type 2 (HSV-2) in 85-90% of cases and herpes simplex virus type 1 (HSV-1) in 10-15% of cases (24). HSV-1 can be transmitted via oral secretions during oral-genital sex. Silent infection is common and may account for more than 75% of viral transmission (25). Up to 80% of women with HSV-2 antibodies have no history of clinical infection (26). The incubation period ranges from 1 to 26 days but is usually short, approximately 4 days. Non-genital infection of HSV-1 during childhood may be protective to some extent against subsequent genital HSV-2 infection in adults.

Primary infection manifests with painful ulcers of the genitalia or anus, and bilateral painful inguinal adenopathy. The initial presentation for HSV-1and HSV-2 are the same (17). A group of vesicles on an erythematous base that does not follow a neural distribution is pathognomonic for herpes simplex (27). The initial infection is often associated with constitutional flu-like symptoms. Sacral radiculo-myelopathy is a rare manifestation of primary infection that has a greater association with primary anal HSV. Genital lesions, especially urethral lesions, may cause transient urinary retention in women. Recurrent episodes are usually less severe, involving only ulceration of the genital or anal area. Severe disease and ­complications of herpes include pneumonitis, disseminated infection, hepatitis, meningitis, and encephalitis. The diagnosis of genital herpes should not be made on clinical suspicion alone, as the classic presentation of the ulcer occurs in only a small percentage of patients. Viral culture with subtyping has been the gold standard of diagnosis of herpes infection. Recurrences and subclinical shedding are much less frequent for genital HSV-1 infection than for genital HSV-2 infection (28, 29). A patient’s prognosis and the type of counseling needed depends on the type of genital herpes (HSV-1 or HSV-2) causing the infection; therefore, the clinical diagnosis of genital herpes should be confirmed by laboratory testing (30). Cell culture and PCR are the preferred HSV tests for per­ sons who seek medical treatment for genital ulcers or other mucocutaneous lesions. The sensitivity of viral culture is low, especially for recurrent lesions, and declines rapidly as lesions begin to heal. PCR assays for HSV DNA are more sensitive and are increasingly used in many settings (31, 32). PCR is the test of choice for detecting HSV in spinal fluid for diagnosis of HSV infection of the CNS. Viral culture isolates should be typed to determine which type of HSV is causing the infection. Failure to detect HSV by culture or PCR does not indicate an absence of HSV infection, because viral shedding is intermittent. Both type-specific and non-type specific antibodies to HSV develop during the first several weeks after infection and persist indefinitely. Accurate type-specific HSV serologic assays are based on the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Type-specific HSV serologic assays might be useful in the following scenarios: recurrent genital symptoms or atypical symptoms with negative HSV cultures; a clinical diagnosis of genital herpes without laboratory confirmation; or a partner with genital herpes. HSV serologic testing should be considered for persons presenting for an STD evaluation (especially for those persons with multiple sex partners), persons with HIV infection, and MSM at an increased risk for HIV acquisition. Screening for HSV-1 and HSV-2 in the general population is not indicated. Newly acquired genital herpes can cause a prolonged clinical illness with severe genital ulcerations and neurologic involvement. Even persons with first-episode herpes who have mild clinical manifestations initially can develop severe or pro­ longed symptoms. Therefore, all patients with first episodes of genital herpes should receive antiviral therapy as follows: Aciclovir 400 mg orally three times a day for 7-10 days or alternatively © 2014 Wichtig Publishing

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Aciclovir 200 mg orally five times a day for 7-10 days or alternatively Famciclovir 250 mg orally three times a day for 7-10 days or alternatively Valaciclovir 1 g orally twice a day for 7-10 days Human papilloma virus Condylomata acuminata are caused by human papilloma virus (HPV), which is spread by direct skin to skin contact. Risk factors for acquiring HPV include multiple sexual partners, early age on onset of sexual intercourse, and having a sexual partner with HPV. Most infections are subclinical and asymptomatic. The median duration of HPV infection is 8 months (33). Types 6 and 11 of HPV are most often responsible for visible external genital warts. It has been suggested that inoculation occurs at the site of genital microtrauma (34), and in this way, the HPV may be also be also found on the cervix, vagina, urethra, anus, and on mucous membranes such as the conjunctiva, mouth, and nasal passages. The types 16, 18, 31, 33, 35, 39, 45, and 51 are associated with cervical dysplasia and neoplasm in women and squamous intraepithelial neoplasia in men (35-37), and in this context, over 99% of cervical cancers and 84% of anal cancers are associated with HPV, most commonly HPV 16 and 18 (38, 39). Condylomata acuminata are usually asymptomatic and the diagnosis is made through the visualization or palpation of papillomatous genital lesions (Fig. 1). In this setting, the treatment is influenced by the wart size, the wart number, the anatomic site of the wart, the wart morphology, and cost of treatment. Generally, warts located on moist surfaces or in intertriginous areas respond best to topical therapy even if surgical therapy has the advantage of eliminating warts in one shot. Therefore, it appears evident that the choice of therapy is tailored on the basis of the characteristics of the clinical case implicated and on patient compliance. In any case, if you need to perform a non-surgical therapy, the following is suggested: Podofilox 0.5% solution or gel or Imiquimod 5% cream or Sinecatechins 15% ointment Pelvic inflammatory disease Pelvic inflammatory disease comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovrian abscess, and pelvic peritonitis (40). In this setting, N. gonorrhoeae and C. trachomatis are implicated in many cases, and in addition, cytomegalovirus (CMV), M. hominis, U. urealyticum, and M. genitalium might be associated in same cases with PID (41-44). In this way, acute PID is difficult to diagnose due to the wide variation in the symptoms and signs. Many women with PID have subtle or mild symptoms. Delay in diagnosis and treatment probably contributes to inflammatory sequelae in the upper reproductive tract. Laparoscopy can be used to obtain a more accurate diagnosis of salpingitis; however, its use © 2014 Wichtig Publishing

Fig. 1 - Condyloma of urethra and vaginal wall.

is not easy to justify when symptoms are mild or vague. Moreover, laparoscopy will not detect endometritis and might not detect subtle inflammation of the fallopian tubes. Consequently, a diagnosis of PID usually is based on clinical findings. The clinical diagnosis of acute PID is undefined (45, 46). Data indicate that a clinical diagnosis of symptomatic PID has a positive predictive value (PPV) of 65-90% for salpingitis compared with laparoscopy. Although regardless of PPV, no single historical, physical, or laboratory finding is both sensitive and specific for the diagnosis of acute PID. Combinations of diagnostic findings that improve either sensitivity or specificity (i.e., exclude more women who do not have PID) do so only at the expense of the other. In any case because of the difficulty of diagnosis and the potential for damage to the reproductive health of women, healthcare providers should maintain a low threshold for the diagnosis of PID (40). In this way, different diagnostic criteria have been proposed, but we believe that the following are essential: • • • • • •

oral temperature >101°F (>38.3°C); abnormal cervical or vaginal mucopurulent discharge; presence of abundant numbers of White Blood Cell (WBC) on saline microscopy of vaginal fluid; elevated erythrocyte sedimentation rate; elevated C-reactive protein; laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis.

Finally, the most specific criteria for diagnosing PID include: • •

•

endometrial biopsy with histopathologic evidence of endometritis; transvaginal sonography or magnetic resonance imaging techniques showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex, or Doppler studies suggesting pelvic infection; laparoscopic abnormalities consistent with PID.

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Ampicillin/Sulbactam 3 g IV every 6 h with Doxycycline 100 mg orally or IV every 12 h

Recommended therapy PID treatment regimens must provide empiric, broad spectrum coverage of likely pathogens. All regimens used to treat PID should also be effective against N. gonorrhoeae and C. trachomatis because negative endocervical screening for these organisms does not rule out upper-reproductive tract infection. The need to eradicate anaerobes from women who have PID has not been determined definitively. Anaerobic bacteria have been isolated from the upper-reproductive tract of women who have PID, and data from in vitro studies have revealed that some anaerobes (e.g., Bacteroides fragilis) can cause tubal and epithelial destruction. Bacterial vaginosis (BV) also is present in many women who have PID (47, 48). Until treatment regimens that do not adequately cover these microbes have been demonstrated to prevent long-term sequelae (e.g., infertility and ectopic pregnancy) as successfully as the regimens that are effective against these microbes, the use of regimens with anaerobic activity should be considered. Treatment should be initiated as soon as the presumptive diagnosis has been made because prevention of long-term sequelae is dependent on early administration of appropriate antibiotics (49). In case of mild or moderate severity, parenteral and oral therapies appear to have similar clinical efficacy. Recommended parenteral regimen Cefotetan 2 g IV every 12 h or Cefoxitin 2 g IV every 6 h plus Doxycycline 100 mg orally or IV every 12 h Because of the pain associated with intravenous infusion, doxycycline should be administered orally when possible. Oral and Intravenous (IV) administration of doxycycline provide similar bioavailability. Parenteral therapy can be discontinued 24 h after clinical improvement, but oral therapy with doxycycline (100 mg twice a day) should continue to complete 14 days of therapy. When tubo-ovarian abscess is present, clindamycin or metronidazole with doxycycline can be used for continued therapy rather than doxycycline alone because this regimen provides more effective anaerobic coverage. Limited data are available to support the use of other second or third-generation cephalosporins (e.g., ceftizoxime, cefotaxime, and ceftriaxone), which also might be an effective therapy for PID and could potentially replace cefotetan or cefoxitin. However, these cephalosporins are less active than cefotetan or cefoxitin against anaerobic bacteria. Alternatively, the STDs treatment guidelines suggest as follows: Clindamycin 900 mg IV every 8 h with Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 h or

Finally, in same cases, oral therapy can be considered for women with mild-to-moderately severe acute PID. But patients who do not respond to oral therapy within 72 h should be re-evaluated to confirm the diagnosis and parenteral therapy should be administered. The recommended oral regimen provides as follows: Ceftriaxone 250 mg IM in a single dose with Doxycycline 100 mg orally twice a day for 14 days with or without Metronidazole 500 mg orally twice a day for 14 days or Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose with Doxycycline 100 mg orally twice a day for 14 days with or without Metronidazole 500 mg orally twice a day for 14 days.

Conclusions The STDs are pathological conditions that are increasing today compared with the past due to a lowering of the age of onset of sexual intercourse. In this context, the presence of more than one sexual infection by pathogens in the same subject suggests the implementation of a strong prevention by the institutions in order to limit the damage that over time could become very costly due to the necessary treatment of this increasing number of patients. In this regard, the carrying out of screening programs and the establishment of vaccination campaigns for some of the available STDs seem to be the right way even if raising public awareness to this problem is absolutely necessary to achieve the best results.

Disclosures Financial support: The authors have no financial disclosures to make. Conflict of interest: The authors have no conflict of interest.

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