Sexual Transmitted Diseases

Chapter 15

SEXUALLY TRANSMITTED DISEASES 

Acquired Immunodeficiency Syndrome 

• AIDS (acquired immunodeficiency syndrome) is a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV). By damaging immune system, HIV interferes with body’s ability to fight against the organisms that cause disease. Acquired immunodeficiency syndrome (AIDS) is defined in terms of either a CD4+ T cell count below 200 cells per µL (CD4 lymphocyte percentage below 14% are considered to have AIDS) or the occurrence of specific diseases in association with an HIV infection. AIDS is the most advanced stage of infection with HIV. HIV stands for human immunodeficiency virus: H – Human: This particular virus can only infect human beings. I – Immunodeficiency: HIV weaken immune system by destroying important cells that fight disease and infection. V – Virus: A virus can only reproduce itself by taking over a cell in the body of its host.

HIV Structure

• It is around 100 to 120 nm in diameter (around 60 times smaller than a red blood cell) and roughly spherical. It is 20-sided enveloped virus of the lentivirus subfamily of retroviruses. HIV is different in structure from other retroviruses. Two viral strands of RNA are found in core surrounded by protein outer coat. Outer envelope contains a lipid matrix within which specific viral glycoproteins are embedded and these knob-like structures are responsible for binding to target cell.

•  Group Specific Antigen (Gag): Gag proteins are encoded by the gag gene and provide structural elements of the virus. Envelope (Env) gene codes for envelope proteins gp160, gp120 and gp41. These polyproteins will eventually be cleaved by proteases to become HIV envelope glycoproteins gp120 and gp41. gp41 is a transmembrane glycoprotein antigen that spans the inner and outer membranes and attaches to gp120, and both involved with fusion and attachment of HIV to CD4 antigen on host cells. Polymerase (Pol) codes for p66 and p51 subunits of reverse transcriptase and p31 an endonuclease. They are located in the core, close to nucleic acids and responsible for conversion of viral RNA into DNA, integration of DNA into host cell DNA and cleavage of protein precursors.

Pathophysiology

•  After the virus enters the body there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood. This response is accompanied by a marked drop in the number of circulating CD4+ T cells. The acute viremia is almost invariably associated with activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts recover. A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.

• HIV seeks out and destroys CCR5 expressing CD4+ T cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly affected. Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.

Modes of Transmission 

Sexual transmission:

• The most frequent mode of transmission of HIV is through sexual contact with an infected person occurs through unprotected heterosexual contacts. Risk of transmission increases in the presence of many sexually transmitted infections like syphilis, gonorrhea and genital ulcers. 

Exposure to infected blood or blood products:

• The second most frequent mode of HIV transmission is via blood and blood products through needle-sharing during intravenous drug use, needle stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilized equipment. 

Mother to fetus:

• HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk. This is the third most common way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%. Perinatal transmission is variable and dependent on viral load and mother’s CD 4 count. 

Use of contaminated clotting factors by hemophiliacs:

• People living with hemophilia require regular transfusions of clotting factors in order to maintain a normal blood clotting system. Therefore, those hemophilia patients receiving untested and unscreened clotting factors are at an extreme risk for contracting HIV via the blood products.

• Transplantation of infected tissues or organs: The risks of transplant related HIV infection are low. All organ and tissue donors are screened for risk factors and tested for HIV and other infectious agents that potentially could be transmitted through transplantation. 

Primary HIV Syndrome:

• Most people who are infected with HIV experience a short, flu-like illness (also known as seroconversion illness) that occurs two to six weeks after infection. It is estimated that up to 80% of people who are.

• Signs and Symptoms of Common Opportunistic Infections include: • Dry cough or shortness of breath, Difficult or painful swallowing, 

• Diarrhea lasting for more than a week, 

• White spots or unusual blemishes in and around the mouth, 

• Pneumonia-like symptoms, 

• Shaking chills or fever higher than 100 F (38ºC) for several weeks, 

• Vision loss, 

• Nausea, abdominal cramps, and vomiting,

• CD4 count drops below 200 cells per µL, person is considered to have advanced HIV disease: 

•  During late-stage HIV infection, the risk of developing a life-threatening illness is much greater. Examples include: 

• If CD4 count drops below 50 cells per µL –

•  Persistent herpes-zoster infection (shingles),

• Oral candidiasis (thrush),

• Oral hairy leukoplakia, 

• Kaposi’s sarcoma (KS),

• Mycobacterium avium, 

• Cytomegalovirus infections, 

• Lymphoma, 

• Dementia. Most deaths occur with CD4 counts below 50 cells per µL. 

Diagnosis 

• There are several types of tests that screen blood (and sometimes saliva) for HIV infection. Newer tests can detect the presence of HIV antigen, a protein, upto 20 days earlier than standard tests. It is confirmed by demonstrating certain serological tests. Performance of medical tests is often described in terms of:

• Sensitivity: 

• The percentage of the results that will be positive when HIV is present. 

• Specificity: The percentage of the results that will be negative when HIV is not present. All diagnostic tests have limitations, and sometimes their use may produce erroneous or questionable results. 

• False positive: The test incorrectly indicates that HIV is present in a noninfected person

• False negative: The test incorrectly indicates that HIV is absent in an infected person. Tests used for the diagnosis of HIV infection in a particular person require a high degree of both sensitivity and specificity. 

• Antibody Tests: 

• The most common HIV tests look for HIV antibodies in body, rather than looking for HIV itself. ELISA: The enzyme-linked immunosorbent assay (ELISA) was the first screening test commonly employed for HIV. ELISA tests use blood, oral fluid, or urine to detect HIV antibodies. If result from either of these tests is positive, will need to take another test, called a Western blot test, to confirm that result. It can take up to two weeks to confirm a positive result.

• Therapeutic Approach to HIV Infection:

• There is currently no cure for AIDS or HIV infection. Although antiretroviral treatment can suppress HIV and can delay AIDS related illness for many years to live a long and healthy life, it cannot clear the virus completely.

• Non-nucleoside reverse transcriptase inhibitors (NNRTIs): 

• NNRTIs disable a protein needed by HIV to make copies of itself. Examples include Efavirenz, Etravirine and Nevirapine. 

• Nucleoside reverse transcriptase inhibitors (NRTIs): 

• NRTIs are faulty versions of building blocks that HIV needs to make copies of itself. Examples include Abacavir and the combination drugs Emtricitabine and Tenofovir and Lamivudine and Zidovudine. Protease inhibitors (PIs): 

• PIs disable protease, another protein that HIV needs to make copies of itself. Examples include Atazanavir, Darunavir, Fos amprenavir and Ritonavir. Entry or fusion inhibitors: 

• These drugs block HIV’s entry into CD4 cells. Examples include Enfuvirtide and Maraviroc. Integrase inhibitors:

• It is a disabled integrase, a protein that HIV uses to infect CD4+ T cells. The most common integrase inhibitor is Rotogravure. 

Prevention

• Certain educational and motivational programmers can effectively reduce the spread of HIV and AIDS. 

Safe sex practice:

• Such as using latex condoms, are effective in preventing HIV transmission. But there is a risk of getting the infection, even with the use of condoms. 

Abstain:

• (Abstain from sex) Not having vaginal, anal, or oral sex is the surest way to avoid HIV. Abstinence or delay of sexual onset can reduce transmission rate especially in young population who have not started sexual activity. Drug abuse and needle sharing: Intravenous drug use is an important factor in HIV transmission in developed countries. Sharing needles can expose users to HIV and other viruses. Strategies such as needle exchange programs are used to reduce the infections caused by drug abuse.

Body fluid exposure:

• Exposure to HIV can be controlled by employing precautions to reduce the risk of exposure to contaminated blood. At all times, health care workers should use barriers (gloves, masks, protective eyewear, shields and gowns). Frequent and thorough washing of the skin immediately after being contaminated with blood or other bodily fluids can reduce the chance of infection. 

Pregnancy:

• Anti-HIV medicines can harm the unborn child. But an effective treatment plan can prevent HIV transmission from mother to baby. Precautions have to be taken to protect the baby's health. Breast feeding may have to give way to bottle feeding if the mother is infected.

Syphilis

• Syphilis is sexually transmitted infection (STI) caused by the spirochete bacterium Treponema pallidum. This disease can be passed to another person through kissing or close physical contact. The infected person is often unaware of the disease and unknowingly passes it on to his or her sexual partner.

Stages of Disease 

• The symptoms of syphilis developed in three stages, are described below. 

• Stage 1 (Primary syphilis): 

• Symptoms of syphilis begin with a painless but highly infectious sore on the genitals or sometimes around the mouth. If somebody else comes into close contact with the sore, typically during sexual contact, they can also become infected. The sore lasts two to six weeks before disappearing. 

• Stage 2 (Secondary syphilis): 

• Secondary symptoms, such as a skin rash and sore throat develop. These symptoms may disappear within a few weeks, after which person may experience a latent (hidden) phase with no symptoms, which can last for years. After this, syphilis can progress to its third, most dangerous stage.

• Stage 3 (Tertiary syphilis): 

• Around a one third of people who are not treated for syphilis will develop tertiary syphilis. At this stage, it can cause serious damage to the body. The symptoms of syphilis are the same for men and women. Also symptoms are mild and thus can be difficult to recognize. The symptoms develop in three stages: 

• Primary syphilis 

• Secondary syphilis 

• Tertiary syphilis

• Primary Syphilis: 

• The initial symptoms of syphilis can appear any time from 10 days to three months after one have been exposed to the infection. The most common symptom is the appearance of a small, painless sore or ulcer (called chancre). The sore will appear on the part of body where the infection was transmitted, typically the penis, vagina, anus, rectum, tongue or lips. Most people only have one sore, but some people can have more.

• Secondary Syphilis: 

• The symptoms of secondary syphilis will begin a few weeks after the disappearance of the sore. Common symptoms include: 

• A non-itchy skin rash appearing anywhere on the body, but commonly on the palms of the hands or soles of the feet,

• Tiredness, 

• Headaches, 

• Swollen lymph glands, Less common symptoms include:

• Fever, 

• Weight loss,

• Latent Phase:

• Syphilis will then move into its latent (hidden) phase, where one will experience no symptoms, even though person remains infected. Latent syphilis can still be passed on during the first year of this stage of the condition, usually through sexual or close physical contact. However, after a couple of years, one cannot pass the infection to others, even though he/she remain infected. 

• Tertiary Syphilis: 

• The symptoms of tertiary syphilis can begin years or even decades after initial infection. Around a one third of people who are not treated for syphilis develop serious symptoms at this stage. 

Pathophysiology

• The understanding of T. pallidum pathophysiology is impeded by the inability to grow the organism in culture. Thus, knowledge of the growth characteristics and metabolism of this bacterium are quite limited.

• Early local infection: 

• Treponema pallidum initiates infection when it gains access to subcutaneous tissues via microscopic abrasions that occur during sexual intercourse. Despite a slow estimated dividing time of 30 hours, the spirochete evades early host immune responses and establishes the initial ulcerative lesion, the chancre (picture 1). During the period of early local replication, some organisms establish infection in regional draining lymph nodes, with subsequent dissemination.

• Immune response:

• Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood. The host immune response begins with lesion infiltration of polymorphonuclear leukocytes, which are soon replaced by T lymphocytes. In some respects, the immune response to T. pallidum is paradoxical. On one hand, the various immune responses during early infection appear to be efficacious, since they coincide with resolution of the primary chancre, even in the absence of therapy. Despite this apparent immune control, however, widespread dissemination of spirochetes occurs at the same time, leading to subsequent clinical manifestations of secondary or tertiary syphilis in untreated patients.

Causes

• Syphilis is caused by the bacteria Treponema pallidum. 

• The bacteria can enter one's body if he/she have close contact with an infected sore, normally during vaginal, anal or oral sex or by sharing sex toys.

Diagnosis 

• Physical examination: 

• Syphilis is diagnosed by examine the genitals. For men, it involves examining the penis, foreskin and urethra (the hole at the end of the penis where urine comes out). For women, it involves an internal examination of the vagina. Both men and women may also have their anus examined.

• Blood tests: 

• If one is infected with syphilis, then his/ her body produces antibodies (proteins released as part of immune response) against the syphilis bacteria. Therefore, one way to determine whether one have syphilis is to have a sample of blood tested for the presence of these antibodies. A positive result (antibodies present) indicates that one can either have the infection or used to have it (because the antibodies can remain in the body for years, even after a previous infection was successfully treated).

• Venereal Disease Research Laboratory test (VDRL): 

• The VDRL test is a screening test for syphilis. It measures substances, called antibodies that body may produce if a person comes in contact with the bacteria that causes syphilis. This bacterium is called Treponema pallidum. 

• Swab test: 

• If sores are present, a swab (like a cotton bud) will be used to take a small sample of fluid from the sore. This is then either looked at under a microscope in the clinic or sent to a laboratory for examination.

 Prevention 

• Protected physical contact through the use of condoms reduces the risk of infection. 

• Promoting sex-education among teenagers. 

• Providing awareness among the population about their sexual health especially in high risks population (high risks population involves sex workers and their partners, Intravenous drug users, truck drivers, labor migrants, refugees and prisoners). People with syphilis should refrain from any sexual contact fora least 1 week after completing treatment or until the lesions of early syphilis (if they were present) are fully healed. People with syphilis should also refrain from any sexual contact until sexual.

• Follow-up blood tests must be done to make sure that treatment has cleared the infection. 

• Pregnant women are screened for syphilis in early pregnancy and again in late pregnancy if they are at increased risk of acquiring syphilis. Testing to exclude other sexually transmitted infections advisable. 

Gonorrhea 

• Gonorrhea is a sexually transmissible infection (STI) caused by bacteria known as Neisseria gonorrhoeae (gonococcus). It usually affects the genital area, although the throat or anus may also be affected. Gonorrhea affects both men and women and is easily transmitted during vaginal intercourse. can also be transmitted during anal or oral sex. Gonorrhea is transmitted from any kind of sexual contact, including: - Vaginal intercourse - Anal intercourse - Oral intercourse (both giving and receiving)

Pathophysiology 

• Gonococci are readily seen in smears (urethral, endocervical, or conjunctival exudates) and cultures, and appear as bean shaped pairs, with the flat sides apposed. The organisms are cultured from tampons, urethral swabs, urine, specimens from endocervix, vagina, anus, and pharynx. Gonorrhoeic begins as a surface infection of the mucous membranes, that is, a catarrh. The bacteria attach to and spread along the cells of the surface mucous membranes, after which they invade superficially and provoke acute inflammation. The mucous membranes of the urethra, endocervix, and salpinx are characteristic sites.

• Women (and to a lesser extent men) may also develop bacteremia, producing disseminated gonococcal infection, which in turn leads to monoarthritic or polyarthritis. Neonatal infections from infected amniotic fluid or an infected birth canal result in symptoms within a few days after birth. These infections involve the conjunctiva and constitute a major cause of blindness. Other sites of neonatal infection are the pharynx, respiratory tract, vagina, anus, leptomeninges, joints and blood. Uncomplicated gonococcal infections of the urethra and endocervix are treated with penicillin and other antibiotics. Neisseria gonorrhea is displaying increasing resistance to penicillin. Penicillinase producing strains are especially common in Africa and Asia. 

Signs and Symptoms 

• Both men and women may have gonorrhea without having any symptoms and so can be infected, or spread infection, without knowing anything is wrong. Some men never develop symptoms, but most do. Symptoms that may occur include.

• Throat and anal infections can occur following receptive oral and anal intercourse and infections at these sites are often without symptoms. 

• Joint pain and infection (arthritis). 

• Conjunctivitis (inflammation of the lining of the eyelids and eye) in both adults and children. Babies born to infected mothers can become infected as they pass through the infected cervix and may develop gonococcal conjunctivitis soon after birth. 

• Having any sexually transmitted infection (STI) increases the risk of HIV infection if exposed to HIV virus while the other infection is present. 

Men

• In addition to the above, gonorrhea in men causes’ urethritis (infection of the urethra, the urinary canal leading from the bladder to exit at the tip of the penis) causing: 

• A burning sensation in the penis when urinating. 

• A white or yellow pus-like discharge from the penis (may be observed in underwear). 

• Swelling and pain in the testicles, which can occur if the gonorrhea infection goes untreated.

Women

• In addition to the above, gonorrhea in women usually affects the cervix (opening of the uterus at the top of the vagina) causing:

• An unusual vaginal discharge. 

• Discomfort on urination. 

• Bleeding between periods, often after having sex. 

• Pain while urinating or passing water. 

• The infection may spread from the cervix to the fallopian tubes, causing pelvic inflammatory disease (PID). Pelvic inflammatory disease due to gonorrhea is often without symptoms, but there may be:

•  Fever, 

•  Low abdominal pain, 

•  Pain on intercourse. If untreated, pelvic inflammatory disease may lead to scarring of the fallopian tubes and ectopic (tubal) pregnancy or infertility. 

Risk Factors 

• Risk factors for gonorrhea include the following:

• Sexual exposure to an infected partner without barrier protection (e.g., failure to use a condom or condom failure),

• Multiple sex partners, 

• Male homosexuality, 

• History of concurrent or past STDs,

• IV drug users, 

• Use of crack cocaine,

• Early age of onset of sexual activity, 

• Pelvic inflammatory disease (PID) - Use of an intrauterine device (IUD). 

Diagnosis 

• The determine whether the gonorrhea bacterium is present in body, analyze a sample of cells. Samples can be collected by:

• Urine test: This may help to identify bacteria in urethra.

• Swab of affected area: A swab of throat, urethra, vagina or rectum may collect bacteria that can be identified in a laboratory.

• Traditionally, gonorrhea was diagnosed with gram stain and culture; PCR-based testing methods are common. All people testing positive for gonorrhea should be tested for other sexually transmitted diseases such as chlamydia, syphilis, and human immunodeficiency virus. 

Treatment 

• Antibiotic resistance has developed to a number of agents, including macrolides, clindamycin and rifampin. Ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment.

• CDC recommendation for uncomplicated gonorrhea: 

• Ceftriaxone 125 mg single IM dose or Ciprofloxacin 500 mg single oral dose plus doxycycline 100 mg twice daily for 7 days or Erythromycin 1 g single oral dose.

Prevention 

• Practice safer sex.

• No sex until antibiotic treatment is completed, and usual sexual partner has completed treatment.

• A follow-up test must be done to make sure that treatment has cleared the infection.

• All sexual partners need to be contacted, tested and treated, if indicated. Even if partners have no symptoms, they may be able to transmit infection to other sexual partners. 

• Testing to exclude other sexually transmitted infections is advisable.