Approach in sexually transmitted diseases

Abstracts

As doenças sexualmente transmissíveis estão entre os problemas de saúde pública mais comuns em todo o mundo. Entre suas consequências estão a infertilidade feminina e masculina, a transmissão de mãe para filho, determinando perdas gestacionais ou doença congênita, e o aumento do risco para a infecção pelo HIV. Dessa forma, este guideline tem o objetivo de contribuir para melhorar a qualidade de atenção às pessoas com infecções sexualmente transmissíveis mais frequentes no Brasil, trazendo de forma didática e concreta o estado atual dos conhecimentos para os dermatologistas e médicos em geral que atuam no atendimento dessas pessoas e as principais recomendações para o diagnóstico e tratamento das doenças sexualmente transmissíveis mais recorrentes.

Cancróide; Doenças sexualmente transmissíveis; Doenças sexualmente transmissíveis; Doenças sexualmente transmissíveis; Doenças sexualmente transmissíveis; Gonorréia; Granuloma inguinal; Linfogranuloma venéreo

REVIEW ARTICLE

Walter Belda Junior^I; Ricardo Shiratsu^II; Valdir Pinto^III

^IResponsible for the Department of Sexually Transmitted Diseases /AIDS, Brazilian Society of Dermatology. Post-doctorate Degree in Dermatology, Universidade Estadual de Campinas (UNICAMP). Assistant Professor, Ph.D., Department of Dermatology, Faculdade de Medicina da Universidade de Sao Paulo (FMUSP) – Sao Paulo (SP), Brazil.

IIVolunteer Assistant Professor, Department of Dermatology, Universidade Federal de São Paulo (UNIFESP) – Sao Paulo (SP), Brazil

IIIMinistry of Health. National Program of Sexually Transmitted Diseases

Mailing Address

ABSTRACT

Nowadays, sexually transmitted diseases are one of the most common public health issues. Among its consequences are the possibility of transmission from mother to baby – which may cause miscarriages and congenital disease, male and female infertility, and the increase of HIV infection risk. Therefore, the main goal of these guidelines is to contribute to the improvement of the treatment for sexually transmitted diseases patients by presenting to the medical community how today's science stands on the matter and also what the recommendation for diagnosing and treating a patient are.

Keywords: Chancroid; Gonorrhea; Granuloma inguinale; Lymphogranuloma venereum; Sexually transmitted disease; Sexually transmitted disease/diagnosis; Sexually transmitted disease/etiology; Sexually transmitted disease/therapy

INTRODUCTION

In 1999, the World Health Organization (WHO) estimated a total of 340 million new cases of curable sexually transmitted diseases (STD) per year all over the world among subjects aged 15 to 49 years amounting to 10 to 12 million cases in Brazil. Other some millions of incurable STD (viral), including genital herpes, human papilloma virus infections, hepatitis B and HIV infections occur annually ¹.

Among women with untreated infections by gonorrhea/ Chlamydia, 10 to 40% develop pelvic inflammatory disease (PID). Among them, more than 25% will become infertile – considering that the rate of infertility caused by non-infectious causes is estimated 3 to 7%. Studies conducted in developed countries indicate that women who have had PID are six to ten times more likely to have ectopic pregnancy, being that ectopic pregnancy contributes to more than 15% of maternal death ².

Spontaneous abortions, stillbirths, low birth weight, congenital and perinatal infections are associated with untreated STD in pregnancy ³. Among men, Chlamydia has become an important cause of fertility if not properly treated ^{4, 5, 6.}

Despite that, sexually transmitted diseases have only regained importance as a public health issue after the AIDS epidemics. Studies have shown that people with STD and non-ulcerative genital infections have 5 to 10 times higher risk to get infected by HIV, which is 18 times higher for those with ulcerative diseases ⁷.

Conversely, if HIV holder also has STD, HIV will be more easily transmitted to his partners. The mean concentration of HIV in seminal liquid is eight times greater in men with urethritis, without any difference in serum concentration. After treatment, seminal concentration is comparable again ⁸. HIV is also present in cervical-vaginal concentration in a frequency twice higher among women with gonorrhea, three times greater in the presence of Chlamydia and four times greater if there is ulceration of cervix or vagina ⁹. Bacterial vaginosis of endogenous origin doubles the risk of HIV infection, and it has significant implications in the gestational period, increasing the risk of prematurity and puerperal infection ^{10, 11, 12}.

Notifiable STD in Brazil are AIDS, HIV in pregnancy and exposed child, syphilis in pregnancy and congenital syphilis. To other STD, there is no system of required notification and the absence of population study hinders the visibility of the problem and the implementation of priority interventions and assessment of their effectiveness ¹³.

MAIN CLINICAL SYNDROMES

• ACQUIRED SYPHILIS

Chronic infectious disease, transmitted by sexual intercourse and sometimes by the placenta. It is characterized by long periods of clinical remission and the capacity to reach multiple organic systems, producing skin, mucosa, cardiovascular and nervous lesions.

Etiology

Epidemiology

^{14, 15}

Transmission

Transmission takes place by direct contact with open lesions, transfusion of blood contaminated with acquired syphilis and via transplacental transmission in congenital syphilis. Treponema is capable of penetrating through normal skin and mucosa, but its penetration is facilitated when there is continuity solution. It quickly multiplies on the infected epithelium, and by lymphatic route it attacks the regional ganglia, where it is also quickly multiplies. Its dissemination is also immediate by hematogenic route. Thus, it invades the whole organism, and even when symptoms are local, generalized infection takes few hours. There are reports of accidental inoculation by manipulation of contaminated lesions by physicians, dentists and laboratory technicians.

Clinical Manifestations

¹⁶

Laboratory Work Up

Darkfield microscopy

The possibility of negative results in the test may be related to:

- patient using local or systemic anti-treponema medication

- chancre older than 3 weeks of progression

- non-representative sample

- non-syphilitic process

Serologic Tests:

Non-Treponemic tests (cardiolipidic or reagins)

Given that they are non-treponemic reactions, they are not specific and in addition to being positive for other treponematosis such as bouba and pinta, they may be present in other diseases than syphilis; in such cases they are named biological false-positive serologic reactions, whose main causes are:

1. Error in execution of the technique

2. Acute causes

• Infectious mononucleosis

• Viral Pneumonia

• Infectious hepatitis

• Herpes simples and zoster

• Measles

• Lymphogranuloma Venereum

• Vaccination (yellow fever and typhoid fever)

• Pregnancy

3. Chronic causes

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Autoimmune hemolytic anemia

• Nodous periartheritis

• Thyroiditis

• Chronic hepatitis

• Hansen's disease

• Tuberculosis

• Leptospirosis

• Malaria

• Visceral leishmaniasis

Treponemic tests

^{16, 17}

The most widely used tests are:

2. Reiter Protein Complement Fixation (RPCF)

3. FTA-200

4. FTA-abs (Fluorescent Treponemal Antibody-absorbed Test)

5. Treponema pallidum Hemagglutination (TPHA)

6. IgM-TPHA

Management

Thus, the recommended dose for recent syphilis management (primary, secondary and latent with less than one year of progression) is Penicillin Benzathine 2.400.000 IU, intramuscular, single dose. For latent, late, cutaneous and cardiovascular syphilis, the recommendation is Penicillin Benzathine 7.200.000 IU, intramuscular, divided into three weekly doses of 2.400.000 IU. In cases of allergy to penicillin, the following therapeutic regimens are recommended: recent syphilis - Doxycycline 100 mg PO, BID for 15 days; Tetracycline 500 mg PO, TID for 15 days; Erythromycin 500 mg PO, TID for 15 days and, Ceftriaxone 250 mg IM/day for 10 days. In latent, late, cutaneous and cardiovascular syphilis: Doxycycline 100 mg PO, BID for 4 weeks; Tetracycline 500 mg PO, TID for four weeks and, erythromycin 500 mg PO, TID for 4 weeks. Some authors suggest the use of azythromycin to treat syphilis, but there are reports of therapeutic failures. ^{18, 19, 19}

Cure Control

¹⁶

• GONORRHEA

It is an infectious-contagious disease, pandemic, inter-human, caused by diplococcus (Neisseria gonorrhoeae) and sexual transmission, even though it may exceptionally be caused by indirect contamination, but it does not provide immunity. In general, it is a urethral or uterine cervix infection that may propagate to glands and neighboring organs by ascending route; in some few cases, primary local infection is extra-genital, causing conjunctivitis, ophthalmia, pharyngitis and anoretitis. Similarly to any infectious process, it is not always localized because depending on the immune status of the host, it may lead to sepsis and general and systemic manifestations.

Epidemiology

Etiological agent

Clinical Manifestations

In women, most cases are simpler, translated only as endocervicitis ²¹.

Complications in men:

• Balanoposthitis

• Stones that cross to the urethra

• Spontaneous perineal pain

• Prostatitis

• Epididymitis

• Cystitis

Complication in women:

• Bartholinitis

• Adnexitis

• EXTRA-GENITAL GONORRHEA

Ophthalmic: It is characterized by conjunctivitis, initially serous, which becomes progressively purulent, viscous, yellowish, followed by palpebral and conjuctival edema.

Rectal: The main symptoms are tenesmus, anal pruritus, painful evacuation and mucous-purulent rectal secretion. Rectoscopy may show purple and edematous mucosa, recovered with abundant suppuration with multiple erosions.

• GONOCOCCAL PHARYNGITIS

Disseminated

Differential diagnosis

Laboratory Work Up

²²

2) Culture: enriched and selective means are recommended, which ensures growth and development of neisseria. They require CO2 atmosphere of about 3-5% and humidity rate of 90% at temperature of 35.5º C to 36.5º C. ^23,24

Among the most used culture media there are modified Thayer-Martin, Martin Lewis and NYC (New York City). ²⁵

Management

^26,27,28,29

• Canchroid

Sexually transmitted disease, of acute progression, caused by gram-negative bacillus and clinically characterized by the presence of painful ulcerations of varied sizes, irregular margins and frequently involved by bright erythematous halo located in the genital, anal or anogenital regions, followed or not by satellite adenopathy.

Epidemiology

Etiology

Clinical Manifestations

^30,31,33

Differential diagnosis

Laboratory Work Up

2) Culture: it is difficult to grow the bacteria, even when using the best media available. The most recommended media are Nairobi, Johannesburg and enriched agar chocolate. The addition of vancomycin antibiotic in the enriched agar chocolate medium intends to inhibit the growth of gram positive bacteria, normally present in the collected clinical sample .^33,34,35

Management

^38,394040

• LYMPHOGRANULOMA VENEREUM

Lymphogranuloma venereum (LGV) is an infectious contagious disease of inflammatory and invasive nature of the urogenital tract that is caused by Chlamydia trachomatis. In many parts of the world, VLG has become an important cause of anogenital disease among men who have sex with other men ⁴¹.

LGV is caused by invasive serotypes L1, L2 and L3 of Chlamydia trachomatis in contrast with serotypes A-C of this agent, which cause ocular infection, such as trachoma, and the more common serotypes D-K that cause genital infections ⁴².

Epidemiology

LGV is a relatively rare disease in industrialized countries, but it is endemic in parts of Africa, Asia, South America and the Caribbean ⁴³.

The incidence of infection by Chlamydia trachomatis after sexual contact is unknown, but probably it is smaller than gonorrhea and canchroid. The peak of incidence of the infection is between the second and third decades of life, the most active period of the sexual life. The period of sexual transmissibility in infected men is about three weeks after the regression of the primary lesion. Among women, the period of transmission is unknown, but it may probably last for months, given that the cervix can remain indefinitely infected ⁴⁴.

Clinical Manifestations

⁴⁵

Two adenomegalias separated by Poupart ligament are characteristics of this disease. Male homosexuals and women after sexual anal intercourse may develop hemorrhagic proctitis or proctocolitis in acute stages of LGV. Primary symptoms are anal pruritus, mucoid rectal secretion and localized pain. The clinical landmark of anorectal LGV is revealed next: rectal muco-purulent secretion ⁴⁴. Proctitis may generate diarrhea or constipation, and in classical proctitis, tenesmus is detected. The tertiary stage refers to late complications that affect the rectum and the genitals, including elephantiasis. These late complications are more common among women and are named esthiomene ⁴⁶.

Differential diagnosis

Laboratory Work Up

Alternatively, Chlamydia trachomatis may be identified by direct microscopic fluorescence using a conjugate of monoclonal antibodies in the material collected from the blister or ulceration. This method requires fluorescence microscope as well and a highly trained technician to execute and interpret the test ⁴³.

Management

⁴⁵

Other drugs may be used, such as chloramphenicol, rifampicin and Thiamphenicol.

• DONOVANOSIS

Donovanosis is a chronic, progressive and indolent bacterial disease that affects preferably the skin and genital and perigenital mucosa. It is frequently associated with sexual transmission, but it has low infectivity.

Etiology

^47,48

Epidemiology

⁴⁹

It is a disease that affects almost exclusively adults in the age range 20-40 years. Cases in children are frequently associated with contact with affected adults, not necessarily by sexual abuse.

Clinical Manifestations

⁵⁰

Clinical manifestation starts with papules or subcutaneous nodules that may progress with superficial ulceration. They grow slowly, without causing pain, and become more definite, granulomatous, with centrifugal and serpiginous character, easily bleeding. They may be self-inoculated and multiple. Typically, there is no adenitis in donovanosis. In addition to anal and perianal region, the other areas of extragenital involvement are: lips, gums, jugal mucosa, mandible, palate, pharynx, larynx, neck, nose, ophthalmic region, scalp, chest (infra-mammary sulci), axilla, abdomen, arms, legs, bones (especially the tibia). Oral lesions are the most frequent ones, and teeth losses indicate bone impairment ^{50, 51}. Dissemination to abdominal cavity, intestines, spleen, liver, lungs, uterus and ovaries has already been reported and it is more frequently seen in endemic areas.

Laboratory Work Up

In addition to clinical pathology exam, transmission electron microscopy may be used to assess the ultrastructural characteristics of K. granulomatis of different species. The culture of the agent is difficult and it is not available as a routine. The combined culture with mono-layer cells has been described using human monocytes, Hep-2 cells and peritoneal macrophages of mice 52. The gene detection technique using polymerase chain reaction (PCR) that enables reclassification of donovanosis agent has its diagnostic application restricted to programs to eradicate the disease ^{53, 54}.

Management

The following therapeutic regimes are recommended: 1) Azythromycin 1 g PO in the first day, followed by 500 mg PO/day or Doxycycline 200 mg PO/day up to clinical cure. 2) Doxycycline 200 mg PO/day up to clinical cure. 3) Erythromycin 2 g PO/day up to clinical cure. 4) Tetracycline 2 g PO/day up to clinical cure. 5) Sulfamethoxazole/Trimethoprim (400/800) 2 pills PO twice a day for at least 14 days. Other antibiotics may also be used with satisfactory therapeutic responses, such as ceftriaxone, norfloxacin, trovofloxacin and Thiamphenicol ^{49,50,55,56,57}. To pregnant patients and positive HIV subjects, we should consider the addition of aminoglycoside since the beginning of treatment.

Essential complementary actions

1) To counsel and provide tests for anti-HIV, VDRL serology and hepatitis B and C;

2) To vaccinate against hepatitis B if the patient is younger than 30 years;

3) To suspend sexual intercourse until treatment is finished and symptoms have disappeared;

4) To emphasize constant use of condoms.

If it is not possible to define the correct etiological diagnosis of the process, it is recommended to use the syndromic approach advocated by the Ministry of Health, as shown below.

Syndromic approach in genital ulcers – Flow chart of genital ulcers (Figure 1).⁵⁶

For the first episode of genital herpes, start treatment as early as possible with Acyclovir 200 mg, 4/4 h, five times a day for 7 days or 400 mg PO, TID for seven days OR Valacyclovir 1 g PO BID for 7 days OR Famciclovir 250 mg PO, TID for seven days. In cases of recurrent genital herpes, start early management with Acyclovir 400 mg PO, TID for 5 days OR Valacyclovir 500 mg PO, BID for five days OR Famciclovir 125 mg PO, BID for 5 days.

In the absence of vesicle lesions, we recommended preventive treatment for the two most frequent causes of genital ulcers – primary syphilis and canchroid, with Penicillin G Benzathine 2.4 million IU, intramuscular, single dose + azythromycin 1 g PO single dose OR ciprofloxacin 500 mg PO, BID for 3 days OR erythromycin estearate 500 mg PO, QID for 7 days.

If lesions last more than 4 weeks, start suspecting of donovanosis, lymphogranuloma venereum or neoplasm. Refer to or perform a biopsy for investigation. Simultaneously, start treatment for donovanosis - Doxycycline 200 mg/day PO until clinical cure OR azythromycin 1 g PO single dose, followed by 500 mg PO/day for 3 weeks.

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*

Trabalho realizado no Departamento de Dermatologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP) – São Paulo (SP), Brasil.

Publication Dates

• Publication in this collection
  03 June 2009
• Date of issue
  Apr 2009

History

• Accepted
  20 Feb 2009
• Received
  20 Feb 2009