**Sexually Transmitted Infections in the Tropics**

John C. Meade and Denise C. Cornelius

*University of Mississippi Medical Center, Department of Microbiology, Jackson, MS USA* 

#### **1. Introduction**

456 Current Topics in Tropical Medicine

Mori Y. & Notomi T. (2009). Loop-mediated isothermal amplification (LAMP): a rapid.

Nagamine K., Hase T, Notomi T. (Jun 2002).Accelerated reaction by loop-mediated isothermal amplification using loop primers. Mol Cell Probes. Vol.16, No.3, pp. 223-9. Nakauchi M, Yoshikawa T, Nakai H, Sugata K, Yoshikawa A, Asano Y, Ihira M, Tashiro M,

Notomi T Okayama H., Masubuchi H., Yonekawa T., Watanabe K., Amino N. & Hase T.

Njiru ZK, Mikosza AS, Matovu E, Enyaru JC, Ouma JO, Kibona SN, Thompson RC,

Parida M, Sannarangaiah S, Dash PK, Rao PV, Morita K. (Nov-Dec 2008). Loop mediated

Polley SD, Mori Y, Watson J, Perkins MD, González IJ, Notomi T, Chiodini PL, Sutherland

Rodrigues Ribeiro Teles FS, Pires de Távora Tavira LA, Pina da Fonseca LJ. (May-Jun 2010)

Tao ZY, Zhou HY, Xia H, Xu S, Zhu HW, Culleton RL, Han ET, Lu F, Fang Q, Gu YP, Liu

Tomita N, Mori Y, Kanda H, Notomi T. (2008). Loop-mediated isothermal amplification

Walker D, Stevens W. (2003). The economics of TB control in developing countries. *Expert* 

Plasmodium vivax infection. *Parasit Vectors*. Vol.4, No.1, pp. 115.

A/H1N1 2009 virus. *J Med Virol*. Vol.83, No.1, pp. 10-5.

parasite DNA. *Int J Parasitol*. Vol.38, No.5, pp. 589-99.

*Rev Med Virol.* Vol.18, No.6, pp. 407-21.

*Chemother*., Vol.15, No.2, pp.62-69.

No. 12, e63.

No.8., pp. 2866-7.

Vol.47, No.3, pp. 139-69.

Vol.3, No.5, pp. 877-82.

*Opin Pharmacother*. Vol.4, No.3, pp. 359-68.

Accurate, and cost-effective diagnositic method for infectious diseases, *J.Infect* 

Kageyama T. (Jan 2011). Evaluation of reverse transcription loop-mediated isothermal amplification assays for rapid diagnosis of pandemic influenza

(2000). Loop-mediated isothermal amplification of DNA, Nucleic Acids Res. Vol.28,

Ndung'u JM. (Apr 2008). African trypanosomiasis: sensitive and rapid detection of the sub-genus Trypanozoon by loop-mediated isothermal amplification (LAMP) of

isothermal amplification (LAMP): a new generation of innovative gene amplification technique; perspectives in clinical diagnosis of infectious diseases.

CJ. (Aug 2010). Mitochondrial DNA targets increase sensitivity of malaria detection using loop-mediated isothermal amplification. *J Clin Microbiol*. Vol.48,

Biosensors as rapid diagnostic tests for tropical diseases. *Crit Rev Clin Lab Sci*.

YB, Zhu GD, Wang WM, Li JL, Cao J, Gao Q. (Jun 2011) Adaptation of a visualized loop-mediated isothermal amplification technique for field detection of

(LAMP) of gene sequences and simple visual detection of products. *Nat Protoc*.

The burden of sexually transmitted infections (STIs) on the health and well-being of the population in the developing world is considerable. The World Health Organization (WHO) estimates that there are 340 million new cases of curable STIs in the world each year; 174 million new cases of trichomoniasis, 92 million new cases of *Chlamydia* infection, 62 million cases of gonorrhea, and 12 million new cases of syphilis (Table 1). Approximately three quarters of these infections are in countries encompassing tropical regions of the world in Latin America, sub-Saharan Africa, and South and Southeast Asia. The prevalence of viral STIs is even higher; infection with Herpes simplex virus-2 (HSV-2) is the most common STI worldwide and as many as 50% of sexually active individuals will be infected with human papillomavirus (HPV) during their life. The prevalence of STIs is considerably greater than many classical tropical diseases and it is unfortunate that they do not receive more attention and resources from international programs and donor groups. The public health impact of these diseases extends well beyond the immediate effects and morbidities of infection. STIs have been implicated in facilitating acquisition and transmission of HIV, in pregnancy complications such as pre-term births, low birth weight infants, stillbirth, neonatal death and blindness, in the inducement of cervical and prostate cancers, and in increased risk of pelvic inflammatory disease and infertility. Failure to diagnose and treat STIs at an early stage thus increases the already substantial burden these conditions impose on the populations of developing countries. Although effective diagnostic tests and treatments are available for these STIs, they are often unavailable or inaccessible in resource-limited tropical settings. As a consequence, syndromic management of STIs remains the option of choice for individual case management. The inadequate public health response coupled to ongoing socioeconomic and demographic trends have led to an epidemic of STIs in many countries in the developing world. The development of antimicrobial resistance is an ongoing problem and new agents are often much more expensive, increasing the burden of control. The economic costs of these diseases and their infection sequelae place a considerable burden on national health budgets and household income. In developing countries, STIs are among the top five reasons for which adults seek medical care. Due to the prevalence and public health implications of STIs in the tropics a discussion of STIs should be included in any compilation of tropical medicine.

This chapter will cover sexually transmitted infections caused by *Trichomonas vaginalis* (trichomoniasis), *Chlamydia trachomatis* (chlamydia and lymphogranuloma venereum), *Neisseria gonorrhoeae* (gonorrhea), *Treponema pallidum* (syphilis), *Haemophilus ducreyi*

Sexually Transmitted Infections in the Tropics 459

STIs could significantly impact the incidence of HIV transmission and acquisition. The number of individuals co-infected with HIV and an STI are high. Studies show increases in treatment failure of treatable STIs in HIV-positive patients. Studies in several countries show high treatment failure of syphilis in HIV-positive patients and in a trichomoniasis study, 18% of HIV-positive women were *T. vaginalis* positive 1 month after treatment. It is therefore possible that more aggressive treatment of non-ulcerative STIs may be necessary to cure an infection in HIV-positive individuals. STI treatment has been shown to significantly reduce HIV-shedding in both men and women. Follow-up for test of cure is also necessary

The diagnosis and management of STIs in the tropics has a dual nature. Sophisticated testing equipment and facilities comparable to those available in developed nations can often be found in large urban centers and popular resort destinations in developing countries. However, in many parts of the developing world, the absence of etiologic diagnostic capacity due to constraints imposed by cost, lack of equipment or trained personnel, and time management has forced health care providers to rely on a syndromebased approach to STI management. This approach employs clinical algorithms based on an STI syndrome to determine antimicrobial therapy. The following sections discuss management of the most common clinical syndromes encountered in STIs. Sexual partners of the index patient should also be examined for STIs and promptly treated for the same condition as treatment failures are common when partners are not treated. Often, treatment regimens to cover multiple infectious agents are recommended due to the difficulty in distinguishing between the overlapping clinical presentations of different STIs, the high prevalence of mixed infections in many areas, and to ensure adequate therapy in the case of loss to follow-up. Syndromic management enables many STIs to be treated and resolved at local clinics which may lack all but the most rudimentary laboratory capabilities. However, patients that do not respond to therapy or those that show systemic signs indicative of other

disease conditions warrant referral to a clinic with more comprehensive facilities.

facility possessing the resources for a more extensive workup.

*Neisseria gonorrhoeae* and *Chlamydia trachomatis* are the major STI pathogens causing urethral discharge. In the syndromic management scheme, treatment of men with urethral discharge should cover both of these organisms. Treatment regimens may be found in the specific sections describing these STIs. Single-dose therapies are preferred. Whenever possible microscopic examination of the urethral smear should be performed; the appearance of more than 5 polymorphonuclear leukocytes per high power field (x1000) is indicative of urethritis. A Gram stain could also demonstrate the presence of gonococci and permit specific treatment. Patients should return in 7 days if symptoms persist. Treatment failure may be due to drug resistance necessitating use of one of the alternative drugs for these STI agents. Patients indicating poor compliance with therapy or the possibility of re-infection can be re-treated with the same drug regimen. *Trichomonas vaginalis* can also be a cause of urethritis in men. In areas of high local *T. vaginalis* prevalence, treatment for this organism should also be given at this time. If symptoms still persist, the patient should be referred to a

due to the higher risk of treatment failure due to co-infection.

**3. Syndromic management** 

**3.1 Urethral discharge in men** 

(chancroid), *Calymmatobacterium granulomatis* (granuloma inguinale or donovanosis), and the viral STIs, herpes simplex virus and human papilloma virus. Each of these STIs spreads via vaginal, anal, and oral sex, as well as by inoculation of material from infected sores in some cases. All share many common risk factors and higher rates of infection are seen in marginalized populations; persons of low socioeconomic status, commercial sex workers, alcohol abusers, illicit drug users, men who have sex with men, prison populations, uncircumcised men, and those with multiple sex partners or who have partners with multiple sex partners. This chapter will cover both syndromic management of STIs as practiced in most areas of the tropical world (WHO 2003, 2005, 2007b) as well as individual descriptions of these diseases, their clinical presentation, diagnosis, and treatment. The treatment regimens presented are those recommended by the Centers for Disease Control and Prevention (CDC, 2010) and the World Health Organization (WHO, 2005).


Table 1. World Health Organization estimates of new cases of curable sexually transmitted infections and HIV, in millions (WHO, 2001; UNAIDS, 2010).

### **2. STIs and HIV**

It is estimated that there are 34 million cases of HIV in the world with 68% or 22.5 million cases occurring in sub-Saharan Africa, where the prevalence is highest, and 4.1 million in South and Southeast Asia. The emergence of the HIV epidemic has complicated the control of STIs as HIV induced immunosuppression leads many patients to respond poorly to STI treatment regimens, requiring higher drug dosages and longer treatment schedules to affect cure. Sexually transmitted infections (STIs) also facilitate the transmission of other STIs, including human immunodeficiency virus (HIV). Several observational studies have been conducted that conclude there to be a strong association between STI and increased risk of HIV acquisition. An individual with a co-existing STI has a 2-5 fold greater risk of acquiring and transmitting HIV. Increased risk of HIV transmission has mostly been attributed to ulcerative STIs, mainly HSV-1 and 2, but also syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale. For instance the population attributable risk percent of HIV acquisition for HSV-1 and 2 varies from 15-30% in Africa. However, studies also show that non-ulcerative STIs, gonorrhea, *Chlamydia*, and trichomoniasis increase the risk of HIV transmission and acquisition as well. Studies that have examined non-ulcerative STIs and risk of HIV seroconversion have found an odds ratio of 1.8-4.8 for gonorrhea, 1.8-3.6 for chlamydia, and 1.9 for trichomoniasis. Therefore, early diagnosis and treatment of treatable

(chancroid), *Calymmatobacterium granulomatis* (granuloma inguinale or donovanosis), and the viral STIs, herpes simplex virus and human papilloma virus. Each of these STIs spreads via vaginal, anal, and oral sex, as well as by inoculation of material from infected sores in some cases. All share many common risk factors and higher rates of infection are seen in marginalized populations; persons of low socioeconomic status, commercial sex workers, alcohol abusers, illicit drug users, men who have sex with men, prison populations, uncircumcised men, and those with multiple sex partners or who have partners with multiple sex partners. This chapter will cover both syndromic management of STIs as practiced in most areas of the tropical world (WHO 2003, 2005, 2007b) as well as individual descriptions of these diseases, their clinical presentation, diagnosis, and treatment. The treatment regimens presented are those recommended by the Centers for Disease Control and Prevention (CDC, 2010) and the World Health Organization (WHO,

Table 1. World Health Organization estimates of new cases of curable sexually transmitted

It is estimated that there are 34 million cases of HIV in the world with 68% or 22.5 million cases occurring in sub-Saharan Africa, where the prevalence is highest, and 4.1 million in South and Southeast Asia. The emergence of the HIV epidemic has complicated the control of STIs as HIV induced immunosuppression leads many patients to respond poorly to STI treatment regimens, requiring higher drug dosages and longer treatment schedules to affect cure. Sexually transmitted infections (STIs) also facilitate the transmission of other STIs, including human immunodeficiency virus (HIV). Several observational studies have been conducted that conclude there to be a strong association between STI and increased risk of HIV acquisition. An individual with a co-existing STI has a 2-5 fold greater risk of acquiring and transmitting HIV. Increased risk of HIV transmission has mostly been attributed to ulcerative STIs, mainly HSV-1 and 2, but also syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale. For instance the population attributable risk percent of HIV acquisition for HSV-1 and 2 varies from 15-30% in Africa. However, studies also show that non-ulcerative STIs, gonorrhea, *Chlamydia*, and trichomoniasis increase the risk of HIV transmission and acquisition as well. Studies that have examined non-ulcerative STIs and risk of HIV seroconversion have found an odds ratio of 1.8-4.8 for gonorrhea, 1.8-3.6 for chlamydia, and 1.9 for trichomoniasis. Therefore, early diagnosis and treatment of treatable

infections and HIV, in millions (WHO, 2001; UNAIDS, 2010).

2005).

**2. STIs and HIV** 

STIs could significantly impact the incidence of HIV transmission and acquisition. The number of individuals co-infected with HIV and an STI are high. Studies show increases in treatment failure of treatable STIs in HIV-positive patients. Studies in several countries show high treatment failure of syphilis in HIV-positive patients and in a trichomoniasis study, 18% of HIV-positive women were *T. vaginalis* positive 1 month after treatment. It is therefore possible that more aggressive treatment of non-ulcerative STIs may be necessary to cure an infection in HIV-positive individuals. STI treatment has been shown to significantly reduce HIV-shedding in both men and women. Follow-up for test of cure is also necessary due to the higher risk of treatment failure due to co-infection.
