AIDS
AutoImmunoDeficiency Syndrome is a sexually transmitted disease caused by the organism, a retrovirus called Human Immunovirus I and II. This virus has a difference from other viruses which attack the human body. It has the power of replication which allows it to remain unharmed by treatment (Fauci, 2008). The first cases are called HIV
infection when the patients do not show any symptoms. The cases take around 10-15 years to become full blown cases.
There is another difference from other organisms in that it does not produce symptoms related to the HIV. The manifestations are symptoms of other illnesses or opportunistic infections which are exacerbated due to the immunosuppression of the CD4+ cells of the immune system by the HIV. In normal circumstances, the CD4+ cells help to fight disease by response to the invading organism. However HIV infection or AIDS causes an antibody response which is the early response (Zijenah, 2002, p. 34). A higher viral load and a lower CD4+ cells indicate a greater chance for onset of clinical disease (Zijenah, 2002, p.35). These CD4+ cells are damaged and effectively reduced so that they are unable to execute their defensive function. All endogenous and environmental pathogens flourish in the body of the infected person giving rise to many opportunistic infections (Fauci, 2002). Opportunistic infections are syphilis, tuberculosis, protozoal and fungal infections like pneumocystitis carinii pneumoniae, malignancies like Kaposi’s sarcoma and lymphoma, viral infections like Herpes simplex, cytomegalovirus and neurological conditions like AIDS Dementia complex (Carey, 2008, p. 464). Symptoms would be those of the opportunistic infections.
HIV virus is present in all the secretions of the infected person, regardless of whether symptoms are present or not (HIV, Medicine Net). It gets transmitted into the vagina, anal area, mouth, or eyes (the mucus membranes), or with a break in the skin, such as from a cut or puncture by a needle. Transmission of the HIV Virus is through heterosexual sexual activity with an infected partner and by the sharing of contaminated injection equipment (Carey, 2006, p. 464). HIV infection is believed to have originated from the sooty mangabey monkeys of Africa (Carey, 2006, p. 464). Blood transfusions were another mode of transmission long before screening of the blood was done. Accidental pricks by needles in the health care setting are immediately treated with post exposure prophylaxis. Countries which do not have screening measures have transmissions through blood contaminants and needle pricks. Tattooing and body piercing procedures also allow transmission. Vertical transmission from mother to child has been reduced to 8% due to the anti-retroviral therapy (Carey, 2006, p.464). Breast milk transmission is possible. Transmission through saliva, casual contact with feces, urine, sweat or tears of infected persons is scarcely reported. Oral sex also causes only a low transmission. Very little transmission is possible with oral sex and kissing (HIV, Medicinenet).
ART (Anti retroviral therapy) caused an 80% reduction in mortality (WHO, 2002). The HAART (highly active antiretroviral therapy) is followed in the countries with highest burden (Mukherjee, 2008, p. 71). Maximum support and adherence is being provided by health workers who aim at minimizing the resistance to the drugs. A minimum package of the ART is addressed to families for HIV prevention, treatment and care. ART covers the prophylaxis for those with occupational exposure, prevention of the mother to child transmission (PMTCT) and diagnosis and treatment of sexually transmitted diseases (Mukherjee, 2008, p.72).
The more developed countries have seen a dramatic decline in AIDS-related mortality following the HAART, a combination of three drugs (Middleberg, 2003, p. 206). The 46000 AIDS related deaths in 1995 came down to 14000 in 2000 (Middleberg, 2003, p. 207). The HAART costs $10000 per patient per year. The drugs hinder the replication of the HIV by blocking the enzymes reverse transcriptase and protease. The fifteen drugs available are divided into 3 groups by way of action: protease inhibitor (PI), nucleoside analogue reverse transcriptase inhibitors (NRTI) and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI). Using one drug or two drugs is ineffective and may be dangerous (Middleberg, 2003, p. 207). The effective combinations are 1 PI with 2 NRTI, 2NNRTI and 1NRTI and the 3rd possibility 3NRTI. The PI group has the drugs Indinavir, Ritonavir, Nelfinavir, Saquinavir, Amprenavir and Lopinavir. The NRTI group has Zidovudine, Didanosine, Zalcitabine, Tenofovir, Stavudine, Lamivudine and Abacavir. The NNRTI has Nevirapine, Delavirdine and Efavirenze. The therapy only suppresses the level of HIV to undetectable levels and does not cure. HIV/AIDS has no cure (Middleberg, 2003, p. 207).
Many treatment programs are being implemented in poorer countries. The Clinton Foundation Approach is working to reduce drug costs. The Global Fund covers many countries (Mukherjee, 2008, p.72). The President’s Emergency Plan for AIDS Relief (PEPFAR) works in 15 countries of which 12 are in Africa. They provide care and treatment delivery in close relationship with the State Departments. Brazil and Thailand have been leaders in providing care.
Human Pappilloma Virus (HPV)
The most commonly sexually transmitted disease in the United States is HPV and accounts for one third of new Sexually Transmitted Diseases every year. About 30 of the 120 viruses of the human variety in the HPV group infect the anogenital areas (Goldman, 2007, p. 21). The manifestations can range from no symptoms to genital warts to invasive squamous cell anogenital carcinoma. 70% of sexually active people get the infection at some time in their lives. Spontaneous clearance of the infection can occur in 3 years. HPV infects and remains in the moist surfaces of the genital skin, epithelium of the vagina, cervix, rectum and urethra. Non-genital infections also can occur. Initial, recurrent or persistent HPV can cause genital warts. All squamous cell cancer cervix results from persistent HPV or with high risk HPV types (Goldman, 2007, p.21).
The causative organism is the human pappilloma virus which is numbered variously by the gene sequence in the viral DNA and in the order of discovery. HPV have a common structure and genomic organization. The virus is a ‘small non developed virion
with double stranded circular DNA of 7800-7900 base pairs which are enclosed in an icosahedral protein capsid’ (Goldman, 2007, p.26). They have specificity for the locations of their invasion. The infected partner will be shedding the virus when small trauma occurs on the partner’s body parts during sexual activity. Repeated trauma will increase the infectivity. When cell division occurs in the healing process, viral replication simultaneously occurs. The basal cells in the inner labia minora of women, the prepuce and frenulum in men and anal epithelium are the sites of invasion. The virus has an affinity for the rapidly dividing cells of the transitional zone of the cervix also. The virus on entry sheds its protein capsule and remains in the host cell giving the picture of poikilocytosis after pushing the nucleus to one side.
It has an incubation period of 1-8 months when it has no lesions. The active growth phase then starts and causes the first lesion. The virus replicates without depending on the host cell division but induces it to proliferate irregularly leading to flat or papillary warts. Viral counts are maximum in the epithelial calls and this is the time that the infected person approaches for therapy (Goldman, 2007, p. 27). 3 months later, the host ‘s immune response starts. Interferons slow the HPV replication and then the cell mediated immune response begins. The HPV would be cleared by the immunocompetent cell mediated system and cytokine production (interferons α, β, and γ and interleukins).
However the virus is not always detected by the immune system as it remains intracellular as the epithelial cells in the perineum do not always allow the body to detect antigens so the HPV may not be recognized by the immune system (Irany, 1998). Thereby 10-20% of people will have persistent infection.
Transmission occurs during sexual activity mainly. The viruses get implanted in the traumatised microabrasions of skin and mucous membrane even if obvious lesions are not evident. Abrasions allow the vulnerable basal epithelial cells to be exposed for infection. 60-67% of partners get obvious lesions but where they escape detection (Munoz, 2003). 50-55% of men whose partners show cervical HPV illness have penile lesions which are due to HPV (Bleeker, 2003). HPV can be transmitted between women too (Marrazzo, 1998). Transmission can occur through oral-genital contact. 4% of women had both genital warts and buccal lesions. 25% of oral cancers have been associated with high risk HPV (Cox, 2001). Transmission is possible in partners who have anal receptive sex with men and women. However anal lesions are not indicative of anal receptive sex. 83% of women who had anal lesions had them in the vulva, vagina and cervix (Mao, 2003). The transmission can also occur from fomites, sauna and tanning beds. Sex toys, exam tables, doorknobs and contaminated examination lights have transmitted HPV (Perniciaro, 1988). Vertical transmission from mother to child is possible through an infected birth canal. The most critical lesion is respiratory /laryngeal pappillomatosis. Exposure during delivery can also produce genital warts and facial lesions in the infant (Goldman, 2007, p.26).
Lesions that are usually seen are the genital warts in the external genitalia on the vagina, vulva, cervix, anus, mouth and larynx. These warts are asymptomatic for men and women. Occasionally mild infection gives rise to itching, soreness, burning sensation and fissures (Mao, 2003). External genital warts may present as a lump. Infected or large ones may be tender and have spotting and a smell. Dyspareunia or post coital spotting may be the presenting feature of larger internal warts.
The classical picture of an external wart is the condyloma acuminata (Goldman, 2007, p.29). They are white or grey or fleshy colored warty, raised, acuminate, exophytic lesions. Low risk HPV on the mucosal surface has finger-like projections and merges into the color of the surrounding tissue. Pappillomas are another manifestation. They are raised pigmented, slow growing and pedunculated and could be missed for tags on keratinized skin (Goldman, 2007, p.29). Flat genital warts are seen in high risk HPV. The color may depend on how the HPV acts on melanocytes and may vary from hyperpigmented to white to red. Genital warts are the only STD in men to have associated penile infection. External warts in women are found on the vulva, perineum and perianal area while in men they are found in the squamous epidermis of the penis, foreskin, scrotum, perineum and perianal area. Internal warts are found in the urethra, anus, vagina and oral cavity. All areas of friction in sexual activity are prone to warts (Goldman, 2007, p.31).
Without treatment, 70% of people in a study cleared the infection in 12 months.
81% had no virus after 24 months. The median clearance time was 8 months (Ho, 1998). 42.7% women had cervical dysplasia after 3 years but there was total resolution. The higher risk HPV needed more time for clearance.
Treatment is done to remove the visible warts. Mechanical and chemical therapies can reduce the size of the warts and make them amenable to the host’s immune response (Goldman, 2007, p. 33). Podofilox solution, Imiquimod cream, Cryotherapy with liquid probe or surgical removal may be done. Imiquimod creams should be well massaged and kept applied for 6-10 hours every night and then washed off for three times a week. Sexual contact is to be abstained from. Imiquimod triggers the two immune response systems, local interferon and cytokine release (Dahl, 2000). Complete clearance is more seen in women. Recurrence is lesser when compared to other self-applied treatment. Podofilox is for application only on external warts. The application is made 3 times a day for 3 consecutive days followed by no therapy for 4 days. Similar cycles of application 4 times may be needed to clear the warts. The Podofilox obstructs the cell division by disrupting the mitotic spindle in metaphase. Interleukins could also be released inducing immune response and the Podofilox could damage the local blood vessels (Goldman, 2007, p. 37).
Trichloroacetic acid (TCA) and bichloracetic acid (BCA) are provider applied therapies and act as cauteries. They coagulate the proteins in the warts. TCA and BCA are used for external warts and warts on keratinized and mucosal epithelia. The wart will assume a frosted color and detach itself leaving an ulcer which must then be treated. Application must be carefully done as both are caustic agents and a new applicator used for each application (Goldman, 2007, p.38).
Podophylin resin is applied to external warts and urethral meatus warts. It is cytotoxic, antimitotic and causes tissue necrosis. Cryotherapy freezes the water in the mitochondria of the cells and leads to thermally induced cytolysis. Liquid nitrogen also has been used for external warts (Goldman, 2007, p.39).
Herpes
Herpes is a common sexually transmitted disease. 50 million Americans have it.
Herpes means to creep in Greek and refers to the contagious ulcerative illness that appears to crawl on the skin (Parks, 2007, p. 47). Two different types of viruses have been identified. Labial or pharyngeal infection is caused by the HSV-I and is transmitted through non-genital means. HSV 2 is a sexually transmitted virus and affects the genital area mainly. It is the main cause of genital ulcers in the United States. Having HSV 2 increases the risk of HIV and transmission. Its chronicity lasts lifelong and the patient sheds virus even when he is not ill. Vertical or intrapartum transmission causes neonatal deaths. Neurological damage to the child is also possible (Parks, 2007, p. 47).
Transmission occurs very speedily and widely. It is highly contagious. 75% of sexual partners contract the disease. 80% of genital herpes infections are caused by HSV 2.
HSV 2 causes more of recurrent episodes. HSV 1 is seen in homosexual men (16). Most of the transmission seen with HSV is due to shedding of the virus during the asymptomatic period (Wald, 2000). Intimate skin to skin contact with infected person, exposure to infected saliva, semen, vaginal secretions, or fluid from active herpetic lesions all cause transmission (Parks, 2007, p. 50). Transmission does not occur through exposure to fomites (Scoular, 2002).
Three types of infections are seen. The infection is primary when the person infected has it for the first time and he has no antibodies to it. It is termed an initial non primary infection when he has had another HSV infection earlier. As HSV 1 is so common, most genital lesions (HSV 2 usually) are considered initial non primary (Parks, 2007, p.51). Incubation period is 4 days for both types (Kimberlin, 2004). The lesions of primary genital infections are similar in intensity and duration in both types.
The clinical picture starts with widespread multiple and painful macules and papules which then turn into groups of clear fluid filled vesicles and pustules. These rupture to form ulcers. The skin lesions heal by crusting. The mucous lesions have no crusting (Kimberlin, 2004). Scarring does not occur. Secondary infection can complicate the healing process and cellulitis is the result (Parks, 2007, p.51). The women have ulcers at the introitus, perineum, labia and perianal area. Local pain, dysuria, dsypareunia, vaginal discharge and bleeding may present as symptoms. The shedding of the virus continues till the 21st day though the infection is only for 12 days (Patel, 2001). Infection spread by autoinoculation to neighboring and distant sites. 82% of patients with initial infection have urethritis. Cervical infection is seen in 80% women who then have post coital discharge or bleeding. Men have lesions on the penile shaft. Tender inguinal lymphadenopathy accompanies the lesions. Systemic manifestations like fever, malaise, backache, hepatitis and meningitis may occur because of viraemia (Kimberlin, 2004).
36 % women and 10% men have stiff neck, headache with or without fever. 4 % people have viral meningitis. 10-15 % women have urinary retention (Parks, 2007, p. 54).
Initial infections may be atypical in presentation and diagnosis may be missed. Recurrent infections are more common in HSV 2 causing at least one recurrence in the first year. This is accompanied half the time by prodromal symptoms of tingling, itching or pain 2 days earlier or even 5 days (Kimberlin, 2004). The features of the recurrences are less severe. HSV related ulcers are complicated by Candida infection in women. The frequency of recurrences will depend on the immunosuppressive status of the patient (Parks, 2007, p.55).
Treatment for initial and recurrent infections is slightly different by Center for Disease Control and Prevention (Parks, 2007, p. 58). The antiviral agent is used for 7-10 days. Local measures for the lesions to prevent secondary infection are as important. Spread through autoinoculation must be limited. The earlier the treatment is started, the greater will be the effectiveness. Acyclovir was the first drug used for genital herpes. It is a purine nucleoside analog which completely inhibits viral DNA polymerase and terminates the viral chain elongation. The disadvantage is that it has to be given thrice daily and develops resistance but it is cheaper and is used as small tablets or a liquid. Valacyclovir, a prodrug of acyclovir, has better bioavilability and has a twice daily dosage. It is costlier. Famciclovir is oral but more expensive than acyclovir (Diaz-Mitoma, 1998). All oral preparations are equally effective (Yeung Yue, 2002). If resistance to these oral preparations is seen, an intravenous preparation of Foscarnet 40mg/kg body weight every 8 hours is equally effective. Ointment is not advocated anymore due to the danger of autoinoculation. Treatment must be different for people with more than 10 recurrences. Sero-discordant couples have a daily dosage schedule. Higher dosage therapy is advised for immunocompromised patients like HIV patients. Counseling is necessary for this illness as all other sexually transmitted illnesses (Parks, 2007, p. 61)
References
- Arany I, Evans T, Tyring SK. Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals. Sex Transm Infect, 1998; 74:349–353.
- Bleeker MC, Hogewoning CJ, Voorhorst FJ, et al. (2003). “Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia. Int J Cancer 2003; 107:804–810
- Carey, J. W. et al. (2006). “HIV/AIDS Research and Prevention”, Encyclopaedia of Medical Anthropology, Vol 1 part 5 pg 462-479,
- Springer. Part of Springer Science+Business media.
- Cox T, Buck HW, Kinney W, Rubin MM. (2001). “HPV types: natural history and epidemiology. Human papillomavirus (HPV) and cervical cancer. Clinical proceedings.” Washington, DC: Association of Reproductive Health Professionals;
- Dahl MV. (2000). “Imiquimod: an immune response modifier”. J Am Acad Dermatol 2000; 43:S1–S5.
- Diaz-Mitoma F, Sibbald RG, Shafran SD, Boon R, Saltzman RL. (1998). “Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group. JAMA 1998; 280:887–892.
- Fauci AS. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science, 1988; 239:617–622.
- Fauci, A. S., Braunwald, E., Kasper, D. L., Hauser, S. L., Longo, D. L., Jameson, L. J. et al. (2008). “Chapter 182. Human Immunodeficiency Virus Disease: AIDS and Related Disorders”, Harrison’s Online, Harrison’s Principles of Internal Medicine, 17th Edition,
- Goldman, L. (2007). “Human Pappilloma and Genital warts”, Chapter 2 in Current Clinical Practice: Sexually Transmitted Diseases: A practical guide for primary care, (Eds.) A.L.Nelson and J.A.Woodward, Humana Press, Totowa, New Jersey
- HIV, Medicine.Net,Web.
- Medicine.Net.com
- Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. (1998). “Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338:423–428.
- Kimberlin DW, Rouse DJ. (2004). “Clinical practice. Genital herpes” N Engl J Med 2004; 350:1970–1977.
- Mao C, Hughes JP, Kiviat N, et al. (2003). “Clinical findings among young women with genital human papillomavirus infection”. Am J Obstet Gynecol 2003; 188:677–684.
- Marrazzo JM, Koutsky LA, Stine KL, et al. Genital human papillomavirus infection in women who have sex with women. J Infect Dis 1998; 178:1604–1609.23.
- Middleberg, M.I. (2003). “HIV/AIDS and Sexually Transmitted Diseases”. Chapter 8 in Promoting Reproductive Security in Developing Countries, Springer US
- Munoz N, Bosch FX, de Sanjose S, et al. (2003). “Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348:518–527.
- Parks, G. (2007). “Genital Herpes”. Chapter 3 in Current Clinical Practice: Sexually Transmitted Diseases: A practical guide for primary care, (Eds.) A.L.Nelson and J.A.Woodward, Humana Press, Totowa, New Jersey
- Patel R, Boselli F, Cairo I, Barnett G, Price M, Wulf HC. (2001). “Patients’ perspectives on the burden of recurrent genital herpes. Int J STD AIDS 2001; 12:640–645.
- Perniciaro C, Dicken CH. Tanning bed warts. J Am Acad Dermatol 1988; 18:586–587
- Scoular A. Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision. Sex Transm Infect 2002; 78:160–165.
- Wald A, Zeh J, Selke S, et al. (2000). “Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons” N Engl J Med 2000; 342:844–850.
- WHO, Department of HIV/AIDS (2002). Estimates of ARV Treatment Needs 2003–2005.
- Yeung-Yue KA, Brentjens MH, Lee PC, Tyring SK. (2002). “Herpes simplex viruses 1 and 2. Dermatol Clin 2002; 20:249–266.
- Zijenah, L.S. and Katzenstein, D. (2002). “Immunopathogenesis of AIDS” Chapter 3 in AIDS in Africa, Myron Essex et al, Springer 2002