Open Journal of Obstetrics and Gynecology
Vol.05 No.07(2015), Article ID:58080,14 pages
10.4236/ojog.2015.57056

Women and Sexually Transmitted Infections in Africa

Gita Ramjee1,2*, Nathlee S. Abbai1, Sarita Naidoo1

1HIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa

2Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK

Email: *gita.ramjee@mrc.ac.za

Copyright © 2015 by authors and Scientific Research Publishing Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

Received 6 June 2015; accepted 14 July 2015; published 17 July 2015

ABSTRACT

Despite efforts to control the spread of sexually transmitted infections (STIs), these infections are still highly prevalent in the developing world, especially in Africa where the prevalence and incidence of Human immunodeficiency virus (HIV) is also very high. Unfortunately, women bear the disproportionate burden of both STIs and HIV in this region. Early diagnosis, treatment and prevention of STIs is therefore crucial in this population given the strong evidence that some STIs have been shown to facilitate the transmission of HIV. This review summarizes the epidemiology, and management of the common STIs affecting African women, and the health complications associated with these infections in the era of emerging antimicrobial resistance.

Keywords:

Women, Sexually Transmitted Infections, Epidemiology, Management, Antimicrobial Resistance, Human Immunodeficiency Virus

1. Introduction

Sexually transmitted infections (STIs) are among the most prevalent infectious diseases worldwide and are a cause of morbidity and mortality [1] . STIs are a significant public health burden in developing countries predominantly due to their adverse impact on reproductive and child health and their role in facilitating the sexual transmission of Human immunodeficiency virus (HIV) infection [2] . The high prevalence of STIs has contributed to the disproportionately high HIV incidence and prevalence in Africa. According to the World Health Organization Global Health Risks report, approximately 1 million women in Africa die yearly due to infection with HIV, human papillomavirus and other STIs [3] . World Bank estimates indicate that STIs, excluding HIV, are the second most common cause of healthy life years lost by women in the 15 - 44 age group in Africa and account for approximately 17% of the total burden of disease [3] . Controlling STIs is the principal aspect of the WHO’s Global Strategy on Reproductive Health [4] , and essential for achieving Millennium Development Goals 4 (child health), 5 (maternal health), and 6 (HIV prevention) [5] . Early diagnosis of STIs is important, and the treatment of STIs needs to be effective and administered as promptly as possible [6] . In many African countries, STIs are treated using the syndromic approach. Briefly, the syndromic approach is based on managing symptoms according to treatment flow charts, which can be easily followed by clinical staff at all primary health care facilities across the country. Laboratory testing of STI patients is therefore not essential for case management [7] . Several efficacious drugs are available to treat STIs [8] . However, drug resistance to current treatment regimens is a major threat to STI control worldwide. Here, we summarize the epidemiology of STIs in women residing in the African region and discuss diagnosis of these infections, treatment challenges due to the emergence of drug resistance and health complications associated with infections.

2. Epidemiology of Sexually Transmitted Infections

The WHO estimates that about 498.9 million new cases of the four main curable STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum [syphilis] and Trichomonas vaginalis) occur every year globally in adults aged 15 to 49 years. In the African region, the total incidence of curable STIs is 92.6 million, with 8.3 million cases of C. trachomatis, 21.1 million cases of N. gonorrhoeae, 3.4 million cases of syphilis and 59.7 million cases of T. vaginalis [9] . While T. vaginalis and bacterial STIs such as C. trachomatis, N. gonorrhoeae and T. pallidum are curable, viral STIs such as Herpes Simplex Virus (HSV) are deemed to be persistent and incurable [10] . The WHO estimates that 536 million people, aged 15 - 49 are infected with HSV-2 type 2, the causative agent of genital herpes. Annually approximately 23.6 million people in this age group become newly infected with HSV-2 [11] . The epidemiology of each STI is different and is influenced by various factors, including sexual mixing patterns (moderated by protective behaviours), the transmissibility of each pathogen, and the duration of infectiousness (moderated by access to effective treatment), demographics, and social circumstances [12] . The highest rates of incident STIs have been reported for adolescents and young adults [13] .

2.1. Chlamydia trachomatis

Urogenital infection is caused by Chlamydia trachomatis, the most common bacterial STI in the world [14] . In 2008, the WHO estimated that 9.1 million adults were infected with C. trachomatis in the African region [9] . The prevalence of C. trachomatis in women in the African region is 2.6% with a reported incidence of 22.3 per 1000 population [9] . Community-based studies conducted in Sub-Saharan Africa (SSA) have reported prevalence estimates from 1.6% - 3.2% in the general population [15] [16] . However, the prevalence rates in targeted populations have been shown to be higher. In Uganda, the prevalence of C. trachomatis in female adolescents has been shown to be 4.5% [17] . In sex worker populations, the prevalence estimates range from 9% in Kenya to 28.5% in Senegal [18] [19] . In another study of high-risk women from Kenya, the incidence rate of C. trachomatis infections was reported to be 5.0 per 100 person-years [20] . Studies conducted in high-risk women from South Africa have reported prevalence estimates from 5% - 11% [20] - [25] . The risk factors for C. trachomatis infection in African women includes; younger age and having a history of N. gonorrhoeae infection [20] [26] .

2.2. Neisseria gonorrhoeae

Neisseria gonorrhoeae, is the second-most-prevalent bacterial STI globally [27] . Rates of gonorrhoea vary greatly among countries in the developed and developing world. The prevalence of N. gonorrhoeae in women in the African region is 2.3% with a reported incidence of 49.7 per 1000 population [9] . In SSA, an estimated 17 million new cases of N. gonorrhoeae infections occur each year [28] . A study conducted in South Africa and Zimbabwe reported an overall prevalence of 0.7% for N. gonorrhoeae infections in women at risk for HIV [29] . The overall incidence rate for N. gonorrhoeae infections was shown to be 2.4 per 100 woman-years. A higher incidence rate was observed in South African women (3.7 per 100 women years) when compared with women from Zimbabwe (1.3 per 100 woman-years) [29] . Other South African studies have reported prevalence rates for N. gonorrhoeae ranging from 3% - 11% in women from this region [30] - [32] . N. gonorrhoeae has been shown to be more prevalent in high risk groups such as sex workers and women attending STI clinics (10% - 31%) [33] , [34] . The risk factors for N. gonorrhoeae infection in women includes; being <25 years old [35] , having a history of N. gonorrhoeae infection and other STIs, having new or multiple sex partners, inconsistent condom use, commercial sex work and drug addiction [36] [37] .

2.3. Trichomonas vaginalis

Trichomonas vaginalis is the most common, non-viral STI globally [37] . In 2008, the total number of new cases of T. vaginalis in adults between the ages of 15 and 49 was approximately 276.4 million [39] . The prevalence of T. vaginalis in women in the African region was 2.2% with a reported incidence of 146.0 per 1000 population [39] . Trichomoniasis prevalence rates ranging from approximately 6% to 42% have been reported in studies conducted in African countries [30] -[45] . A one year prospective study conducted amongst women in South Africa, Tanzania and Zambia reported the overall incidence of T. vaginalis to be 31.9/100 person-years at risk (PYAR) [46] . Risk factors associated with T. vaginalis infection in African women include; older age, multiple sex partners, being single and unmarried, low socioeconomic status and poor hygiene practises, [44] [47] - [49] .

2.4. Treponema pallidum (Syphilis)

Syphilis is caused by the spirochete Treponema pallidum [50] . The infection is transmitted by sexual contact or through vertical transmission from an infected mother to her baby. The WHO estimated that in 2008 there were 36.4 million adults infected with syphilis globally [39] . In females within the African region the prevalence of syphilis was 3.5% and the incidence was reported to be 8.5 per 1000 population [39] . Syphilis prevalence rates vary depending on the population type and the associated risk factors. In Africa it is estimated that the prevalence ranges from 2.5% to 17% in pregnant women [41] [51] . Prevalence of syphilis was reported to be 9.1% in a cohort of women from a rural area in Mwanza, Tanzania [52] . In a study amongst female sex workers in Kenya, syphilis prevalence was found to be 3.4% [53] . Lower levels of education, early sexual debut, having concurrent partners, and engaging in transactional sex [49] [52] [54] are amongst the risk factors associated with syphilis infection.

2.5. Herpes Simplex Virus

Herpes simplex virus 2 (HSV-2) is one of the most prevalent viral STIs globally, with rates as high as 78% in African women [55] [56] . Data on HSV-2 incidence in women from SSA have reported rates of 6 to 35 per 100 person years (PY) [57] - [60] . In South Africa, the prevalence estimates of HSV-2 infection is reported to be between 40% - 70% [56] [61] [62] . The prevalence of HSV-2 has been shown to be high in populations such as STI clinic attendees and sex workers (SWs) [63] , with some African studies reporting greater than 70% HSV seropositivity in SWs [18] [57] . There are several reports suggesting that HSV-2 is a biological co-factor for HIV acquisition [57] [64] [65] . A meta-analysis performed by Freeman [66] showed that the relative risk of HIV acquisition associated with HSV-2 was 3.1 (95% confidence interval (CI): 1.7, 5.6). It is suggested that HSV-2 infection may contribute to >50% new HIV infections among women in SSA [67] . The factors associated with prevalent HSV-2 infection in women in Africa includes; older age [61] [62] [67] early menarche [68] , low level of education [59] [62] and having a higher number of sex partners [59] [62] .

2.6. Human Papillomavirus

Genital human papillomavirus (HPV) infections, one of the common viral STIs diagnosed worldwide, has been linked to cervical cancer in women [69] . More than 40 known HPV types infect the female genital tract [70] . Genital HPV genotypes are classified into either “high-risk” (HR) or “low-risk” (LR) [71] . The WHO estimates that in 2005 there were approximately 500 000 cervical cancer cases globally [72] . The prevalence of HPV is higher in African women compared to women in any other parts of the world, with the most important types of HPV being 16 and 18 [70] . HPV-16 sero-prevalence has been shown to be the highest in women aged 25 - 40 years. However, HPV-18 sero-prevalence is lower than HPV-16 sero-prevalence and is present in older women [73] . Global data on prevalence of HPV is essential for the implementation of HPV prevention strategies, such as prophylactic vaccines [74] . A comprehensive meta-analysis of HPV genotype prevalence and distribution in Africa conducted by Ogembo and colleagues [75] showed that HPV prevalence rates varied by region. Southern Africa had the highest HPV prevalence of 57.3%, followed by Eastern Africa (42.2%), Western Africa (28.8%) and Northern Africa (12.8%). In a study amongst female sex workers in South Africa the HR- and LR-HPV prevalence was found to be very high at 70.5% (95% CI : 60.5 - 79.2) and 60.2% (95% CI: 49.9 - 70.0) respectively [71] . A prevalence of 33.2% was reported among women, aged 15 - 70 years, undergoing voluntary screening in Benin, West Africa [76] . Factors associated with increased risk of HPV infection include co-infection with HIV or other STIs such as C. trachomatis and HSV-2, micronutrient deficiencies, younger age, increased number of lifetime sexual partners and having had a recent new sexual partner [77] .

2.7. STIs and HIV

In SSA, women comprise 60% of adults living with HIV infection [78] . Sexual transmission is the main route of HIV infection, with an increased risk of infection in women in comparison to men [79] . There are several characteristics of the female reproductive tract (FRT) that increase susceptibility to infection, including local changes induced by infection by other microorganisms [79] . STIs increase susceptibility to HIV, by causing disruption of the genital epithelium, by increasing the number of HIV target cells and by immune activation in the genital mucosa [80] . STIs are major causes of inflammatory cytokine up-regulation and immune cell recruitment to the genital mucosa [81] [82] . Although inflammation can play an important role in STI clearance, it may also cause destruction of infected epithelial layers, allowing STI-associated microbes to access deeper tissues [83] . An association between genital infections and inflammatory cytokine concentrations has been reported in multiple studies. Of the cytokines measured, interleukin (IL)-6 appears to be commonly induced following infection with multiple STIs, while IL-8 production has been associated with trichomoniasis, cervicitis, and yeast infections [84] . Studies conducted in South Africa have shown that C. trachomatis, N. gonorrhoeae and Mycoplasma genitalium infections and elevated cervicovaginal lavage (CVL) concentrations of interleukin (IL)-1β, IL-6, IL-8 and soluble CD40L (sCD40L) were associated with increased risk of HIV acquisition [30] . Several studies have found that women from SSA have increased systemic and genital immune activation compared to women from Europe and North America [85] [86] .

A recent report by Wand and Ramjee highlighted that women who were at risk for STIs, including those with repeated STI diagnoses, were also at risk of acquiring HIV [87] . To date, 10 randomized controlled trials (RCTs) of STI treatment interventions with an HIV endpoint have been completed in SSA. The outcomes of five of these trials are described in the table below (Table 1). Of these trials, only the Mwanza trial [85] , reported a reduction in HIV incidence in the treatment arm. The other trials did not replicate the results of the Mwanza trial due to flaws in the study designs as described recently by Stillwaggon and Sawers [88] .

3. Adverse Impact of STIs on Women’s Health

STIs have been related to a number of adverse pregnancy outcomes such as spontaneous abortion, stillbirth, prematurity, low birth weight (LBW), postpartum endometritis, and various sequelae in surviving neonates [93] . Untreated STIs are linked to congenital and perinatal infections in neonates, especially in high prevalence and

Table 1. Summary of RCTs of curable STIs with an HIV endpoint in Sub-Saharan Africa.

incidence regions [94] . Untreated syphilis in pregnancy can result in stillbirth and neonatal death [94] . Approximately 25% of pregnant women who have untreated syphilis experience stillbirths. Additionally, a 14% neonatal mortality has been recorded [94] . Untreated gonoccocal infections in pregnant women is responsible for approximately 35% of spontaneous abortions and premature deliveries as well as 10% of perinatal deaths [94] . An estimated 30% - 50% of infants born to mothers with untreated gonorrhoea and chlamydial infection develop a serious eye infection (ophthalmia neonatorum), which can lead to infant blindness [94] . Infection with T. vaginalis is also associated with adverse health outcomes for women. In women, T. vaginalis infections results in mild to severe vaginitis [95] and has been associated with an increased risk for HIV infection and cervical cancer [96] . Additionally, T. vaginalis infections may increase the risk of adverse pregnancy outcomes and these include preterm delivery and delivery of a low-birth-weight infant [95] . According to the WHO, cervical cancer caused by HPV is responsible for 11% of deaths globally, and is the primary cause of cancer-related deaths in African countries [3] . It is anticipated that the number of HPV-related cervical cancer cases will double by 2050 as a result of the significant increase of HPV infections in developing countries and the increase in population and life expectancy [90] .

4. Management of STIs

Since the 1990s, the WHO has recommended a syndromic approach for the diagnosis and management of STIs in patients presenting with signs and symptoms of STIs. This approach was developed for particular implementation in countries that have no or limited access to STI diagnostic services. The syndromic management approach allows for immediate treatment based on the presentation of signs and symptoms of infection. Syndromic case management remains the foundation for treatment of STIs in many countries around the world. The WHO supports syndromic case management as a part of its core STI management strategy [97] . The overall objective of syndromic management guidelines is to prevent the transmission of STIs. The management of vaginal discharge syndrome (VDS) and genital ulcer syndrome (GUS) in women presenting with symptoms is described in the table below (Table 2). Male discharge and GUS is more accurately identified when compared to VDS. VDS

Table 2. STI treatment guidelines for women based on syndromic management approach [100] .

can be divided as discharge from the vagina and/or cervix, dysuria, vulvo-vaginal itch and lower abdominal pain. Women with a discharge can present with one or a combination of these symptoms [98] . Despite this, vaginal discharge is often difficult to treat and is not an appropriate lead symptom for the diagnosis of cervical infections because these are mostly asymptomatic [99] . In a cohort of high risk women in South Africa tested for STIs, only 12% of women who tested positive for a STI had visible clinical symptoms. These women would have gone untreated in a syndromic management setting. Symptom driven management of STIs may therefore not be feasible in high risk populations [30] as untreated STIs may facilitate continued transmission of STIs, resulting in genitourinary and maternal complications and an increased risk of HIV acquisition.

5. Treatment Challenges in the Era of Emerging Drug Resistance

Clinical treatment failures for chlamydia are beginning to be reported in the literature. In one report, three chlamydial isolates were shown to be resistant to doxycycline, azithromycin, and ofloxacin [99] . One of the primary reasons for transmission of chlamydia is the frequency of repeat infections [36] . Untreated infections can result in complications such as pelvic inflammatory disease, ectopic pregnancy and infertility [101] . Additionally, infection in pregnant women increases the risk of preterm delivery. C. trachomatis infections also increases the risk of HIV acquisition [102] . Improving partner treatment strategies to reduce repeat infections and validation of new chlamydia rapid tests are essential for infection control. However, based on the difficulties associated with the reduction of chlamydia prevalence there is a need for continued work toward an effective chlamydia vaccine [103] .

Antimicrobial resistance (AMR) is making the clinical management of N. gonorrhoeae increasingly challenging and this challenge has been experienced on a global scale [104] . One of the reasons contributing to AMR, is the remarkable ability of N. gonorrhoeae to develop and acquire antibiotic resistance mechanisms [105] . The emergence of AMR of N. gonnorhoeae to various classes of antibiotics including penicillins, sulfonamides, tetracyclines, quinolones and macrolides has limited the currently available treatment options. In South Africa, in 2003, resistance to ciprofloxacin was reported as a clinical problem based on the sudden appearance of quinolone resistant N. gonorrhoeae (QRNG) at a prevalence of 22% [106] . Third generation cephalosporins are the only remaining class being used however there has already been evidence of resistance to cefixime with verified treatment failures in Japan [107] , Norway [108] and the United Kingdom [109] . Of concern is that the first case of resistance to ceftriaxone has also been detected in Japan [27] .

Presently, in South Africa, antimicrobial resistant N. gonorrhoeae infections is a huge public health issue since there are concerns that N. gonorrhoeae infections may be become untreatable in the coming years [7] . Untreated infections can result in numerous complications such as pelvic inflammatory disease, ectopic pregnancy, tubal infertility, neonatal eye infections, and consequences such as facilitation of HIV co-transmission [104] especially in regions where the prevalence of both these diseases is high [7] [110] . In the absence of a vaccine, antibiotics is the most effective way for curing N. gonorrhoeae infections as well as stopping the local spread of infection [111] . The rapid development and evaluation of new antibiotics for the treatment of N. gonorrhoeae infections is urgently needed. Currently, there are two clinical trials of new regimens being tested [13] .

For more than 20 years Acyclovir (ACV) has been used as the first-line treatment for the management of herpes simplex virus 1 (HSV-1) and 2 (HSV-2) diseases. However, viral resistance towards ACV is increasingly observed [112] [113] . The prevalence of ACV resistant HSV isolates differs for immunocompetent and immunocompromised patients [114] . Previously a low prevalence of resistance to ACV was reported for immunocompetent patients in [115] . However, there was a later report on a prevalence rate of 6.4% for ACV resistance in immunocompetent patients [114] . In the immunocompromised patients, the reported prevalence of ACV resistance has been shown to be higher (3.5% - 6%) [116] .

A vaccine against HSV-2 infection could have tremendous impact on HIV spread [13] , since HSV-2 is a biological co-factor for HIV acquisition [57] [64] [65] . During the development of the vaccine against HSV-2, the following should be taken into account; the viral latency, the herpes immune escape, and the high seroprevalence [117] . The availability of a vaccine will aid in preventing neonatal herpes and alleviating the pain associated with genital herpes symptoms [13] .

Resistance of T. vaginalis strains to metronidazole has been emerging and there is evidence that resistance may be on the increase [118] . In South Africa, a 6% prevalence of metronidazole resistance was reported for women attending an antiretroviral clinic [119] . Other drugs that may have efficacy against T. vaginalis infections include nitazoxanide and miltefosine [96] . However, the appropriate route of administration and safety of these drugs are yet to be published, since nitazoxanide may only be available as an intravaginal gel due to poor absorption in the gut and the safety of miltefosine for pregnant women is yet to be investigated [96] . To this end, continued efforts toward developing trichomoniasis vaccines should be pursued [13] .

6. Interventions for Prevention and Management of STIs in Women

6.1. Condom Use

Both male and female condoms are extensively promoted as an important component of STI control programmes [120] . Consistent and correct condom use should protect an uninfected individual from acquiring an infection (primary prevention) and an infected individual from transmitting infections (secondary prevention) if the site of infection is protected by the condom. In prospective studies, consistent condom use has been shown to reduce, though not eliminate, the acquisition of chlamydia, gonorrhoea, syphilis and genital herpes in men and women, as well as trichomonal and HPV infections in women [121] [122] . The reasons for condom failure are mostly behavioural rather than mechanical (breakage, slippage). Reports from several national surveys conducted in South Africa, Burkina Faso, Ghana, Malawi and Uganda, indicated that women used condoms less consistently than men [123] . This was mainly due to religious beliefs and the inability of women to negotiate condom use with their male partners.

6.2. Vaccines

A milestone in the prevention of cervical cancer in women has been the development of the HPV vaccine. There are currently two commercially available HPV vaccines, CervarixTM (GlaxoSmithKline Biologicals) and GardasilTM (Merck & Co), which are protective against HR-HPV types, 16 and 18 [124] . HPV vaccination programmes will impact significantly in African countries where there are limited screening and treatment facilities to manage HPV-associated cancer [125] . Rwanda was the first country in SSA to introduce school-based HPV vaccination in 2011. Since then other African countries including Uganda, Tanzania, Lesotho and South Africa have implemented the roll out of the HPV vaccine [75] .

6.3. Partnership Interventions

An important component of STI management includes partner notification for STIs which aids in interrupting transmission of infections, averting possible re-infection, and preventing STI-related health complications [126] . Partner management (notification and treatment) is a key component of the syndromic management system. The process of partner notification involves notifying the sexual partners of infected individuals of their exposure, administering presumptive treatment, and providing counseling and education on future STI prevention [127] . Partner notification and treatment may be inadequate due to gender and cultural issues which prevent effective communication between partners and thus impact on their ability to convey information acquired from clinics [128] .

7. Future Research Directions

Although, the syndromic case management remains the foundation for STI treatment in numerous countries around the world including South Africa [97] , there are, however, several limitations of syndromic management including failing to treat asymptomatic infections, over-treatment, as well as poor sensitivity and specificity of algorithms in accurately diagnosing the infections, specifically for women [129] . To address these gaps, inexpensive point of care (POC) tests are now commercially available for screening of STIs [130] . The use of these diagnostic tests could result in the treatment of a larger number of infected individuals as compared to provision of treatment at the return visit [130] . These POC tests may have a significant impact at the population level. This impact can be measured by calculating future prevalence and incidence rates of STIs in the general population. To the best of our knowledge, there have been a limited number of studies that have explored the diagnostic performance as well as the feasibility of introducing STI POC tests in clinical settings in Africa. Such studies are urgently needed, since the data generated from these studies may be used to modify the current STI management algorithm provided the tests are shown to be cost effective with a high sensitivity and specificity.

8. Conclusion

Although STIs may be treated and most are curable, they still remain a major public health problem in developing countries where the HIV epidemic is also severe. Comprehensive STI screening and surveillance progra- mmes should be implemented to assess the true burden of these infections in the African region. Given that many STIs are asymptomatic, integration of STI screening services within HIV testing facilities may allow for more early diagnosis, treatment and prevention of both HIV and STIs in at-risk populations. There still remains an urgent need for female-controlled STI and HIV prevention methods, and the development of more cost-effec- tive rapid POC tests that may be used for efficient diagnosis of STIs in resource-limited settings.

Cite this paper

GitaRamjee,Nathlee S.Abbai,SaritaNaidoo,11, (2015) Women and Sexually Transmitted Infections in Africa. Open Journal of Obstetrics and Gynecology,05,385-399. doi: 10.4236/ojog.2015.57056

References

  1. 1. Tang, V.A. and Rosenthal, K.L. (2010) Intravaginal Infection with Herpes Simplex Virus Type-2 (HSV-2) Generates a Functional Effector Memory T Cell Population That Persists in the Murine Genital Tract. Journal of Reproductive Immunology, 87, 39-44.
    http://dx.doi.org/10.1016/j.jri.2010.06.155

  2. 2. Mayaud, P. and McCormick, D. (2001) Interventions against Sexually Transmitted Infections (STI) to Prevent HIV Infection. British Medical Bulletin, 58, 129-153.
    http://dx.doi.org/10.1093/bmb/58.1.129

  3. 3. World Health Organization (2009) Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks.

  4. 4. World Health Organization (2004) Reproductive Health Strategy to Accelerate Progress towards the Attainment of International Development Goals and Targets.

  5. 5. Sachs, U. and Director, J. (2005) UN Millennium Project. Inventing in Development: A Practical Plan to Achieve the Millennium Development Goals. New York.

  6. 6. Control, C.F.D. and Prevention (2011) Sexually Transmitted Diseases Treatment Guidelines, 2010. Annals of Emergency Medicine, 58, 67-68.
    http://dx.doi.org/10.1016/j.annemergmed.2011.04.006

  7. 7. Crowther-Gibson, P., Govender, N., Lewis, D., Bamford, C., Brink, A., Von Gottberg, A., Klugman, K., Du Plessis, M., Fali, A. and Harris, B. (2011) Part IV. Human Infections and Antibiotic Resistance. South African Medical Journal, 101, 567-578.

  8. 8. Workowski, K.A. and Berman, S.M. (2011) Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines. Clinical Infectious Diseases, 53, S59-S63.
    http://dx.doi.org/10.1093/cid/cir694

  9. 9. World Health Organization (2008) Global Incidence and Prevalence of Selected Curable Sexually Transmitted Infections: Overview and Estimates. Geneva.

  10. 10. Kaushic, C., Roth, K.L., Anipindi, V. and Xiu, F. (2011) Increased Prevalence of Sexually Transmitted Viral Infections in Women: The Role of Female Sex Hormones in Regulating Susceptibility and Immune Responses. Journal of Reproductive Immunology, 88, 204-209.
    http://dx.doi.org/10.1016/j.jri.2010.12.004

  11. 11. Looker, K.J., Garnett, G.P. and Schmid, G.P. (2008) An Estimate of the Global Prevalence and Incidence of Herpes Simplex Virus Type 2 Infection. Bulletin of the World Health Organization, 86, 805A-812A.
    http://dx.doi.org/10.2471/BLT.07.046128

  12. 12. Aral, S. (2002) Understanding Racial-Ethnic and Societal Differentials in STI. Sexually Transmitted Infections, 78, 2-4.
    http://dx.doi.org/10.1136/sti.78.1.2

  13. 13. Gottlieb, S.L., Low, N., Newman, L.M., Bolan, G., Kamb, M. and Broutet, N. (2014) Toward Global Prevention of Sexually Transmitted Infections (STIs): The Need for STI Vaccines. Vaccine, 32, 1527-1535.
    http://dx.doi.org/10.1016/j.vaccine.2013.07.087

  14. 14. Mylonas, I. (2012) Female Genital Chlamydia trachomatis Infection: Where Are We Heading? Archives of Gynecology and Obstetrics, 285, 1271-1285.
    http://dx.doi.org/10.1007/s00404-012-2240-7

  15. 15. Orroth, K., Korenromp, E., White, R., Changalucha, J., de Vlas, S., Gray, R., Hughes, P., Kamali, A., Ojwiya, A. and Serwadda, D. (2003) Comparison of STD Prevalences in the Mwanza, Rakai, and Masaka Trial Populations: The Role of Selection Bias and Diagnostic Errors. Sexually Transmitted Infections, 79, 98-105.
    http://dx.doi.org/10.1136/sti.79.2.98

  16. 16. Pepin, J., Deslandes, S., Khonde, N., Kintin, D., Diakité, S., Sylla, M., Méda, H., Sobela, F., Asamoah-Adu, C. and Agyarko-Poku, T. (2004) Low Prevalence of Cervical Infections in Women with Vaginal Discharge in West Africa: Implications for Syndromic Management. Sexually Transmitted Infections, 80, 230-235.
    http://dx.doi.org/10.1136/sti.2003.007534

  17. 17. Rassjo, E.-B., Kambugu, F., Tumwesigye, M.N., Tenywa, T. and Darj, E. (2006) Prevalence of Sexually Transmitted Infections among Adolescents in Kampala, Uganda, and Theoretical Models for Improving Syndromic Management. Journal of Adolescent Health, 38, 213-221.
    http://dx.doi.org/10.1016/j.jadohealth.2004.10.011

  18. 18. Kaul, R., Kimani, J., Nagelkerke, N.J., Fonck, K., Ngugi, E.N., Keli, F., MacDonald, K.S., Maclean, I.W., Bwayo, J.J. and Temmerman, M. (2004) Monthly Antibiotic Chemoprophylaxis and Incidence of Sexually Transmitted Infections and HIV-1 Infection in Kenyan Sex Workers: A Randomized Controlled Trial. The Journal of the American Medical Association, 291, 2555-2562.
    http://dx.doi.org/10.1001/jama.291.21.2555

  19. 19. Sturm-Ramirez, K., Brumblay, H., Diop, K., Guèye-Ndiaye, A., Sankalé, J.-L., Thior, I., N’Doye, I., Hsieh, C.-C., Mboup, S. and Kanki, P.J. (2000) Molecular Epidemiology of Genital Chlamydia trachomatis Infection in High-Risk Women in Senegal, West Africa. Journal of Clinical Microbiology, 38, 138-145.

  20. 20. Masese, L., Baeten, J.M., Richardson, B.A., Deya, R., Kabare, E., Bukusi, E., John-Stewart, G., Jaoko, W. and McClelland, R.S. (2013) Incidence and Correlates of Chlamydia trachomatis Infection in a High-Risk Cohort of Kenyan Women. Sexually Transmitted Diseases, 40, 221-225.
    http://dx.doi.org/10.1097/OLQ.0b013e318272fe45

  21. 21. Padian, N.S., van der Straten, A., Ramjee, G., Chipato, T., de Bruyn, G., Blanchard, K., Shiboski, S., Montgomery, E.T., Fancher, H. and Cheng, H. (2007) Diaphragm and Lubricant Gel for Prevention of HIV Acquisition in Southern African women: A Randomised Controlled Trial. The Lancet, 370, 251-261.
    http://dx.doi.org/10.1016/S0140-6736(07)60950-7

  22. 22. Ramjee, G., Kapiga, S., Weiss, S., Peterson, L., Leburg, C., Kelly, C. and Masse, B. (2008) The Value of Site Preparedness Studies for Future Implementation of Phase 2/IIb/III HIV Prevention Trials: Experience from the HPTN 055 Study. Journal of Acquired Immune Deficiency Syndromes, 47, 93-100.
    http://dx.doi.org/10.1097/QAI.0b013e31815c71f7

  23. 23. Skoler-Karpoff, S., Ramjee, G., Ahmed, K., Altini, L., Plagianos, M.G., Friedland, B., Govender, S., De Kock, A., Cassim, N. and Palanee, T. (2008) Efficacy of Carraguard for Prevention of HIV Infection in Women in South Africa: A Randomised, Double-Blind, Placebo-Controlled trial. The Lancet, 372, 1977-1987.
    http://dx.doi.org/10.1016/S0140-6736(08)61842-5

  24. 24. McCormack, S., Ramjee, G., Kamali, A., Rees, H., Crook, A.M., Gafos, M., Jentsch, U., Pool, R., Chisembele, M. and Kapiga, S. (2010) PRO2000 Vaginal Gel for Prevention of HIV-1 Infection (Microbicides Development PROGRAMME 301): A Phase 3, Randomised, Double-Blind, Parallel-Group Trial. The Lancet, 376, 1329-1337.
    http://dx.doi.org/10.1016/S0140-6736(10)61086-0

  25. 25. Abdool Karim, S.S., Richardson, B.A., Ramjee, G., Hoffman, I.F., Chirenje, Z.M., Taha, T., Kapina, M., Maslan-kowski, L., Coletti, A. and Profy, A. (2011) Safety and Effectiveness of BufferGel and 0.5% PRO2000 Gel for the Prevention of HIV Infection in Women. AIDS, 25, 957-966.
    http://dx.doi.org/10.1097/QAD.0b013e32834541d9

  26. 26. Radebe, F., Ricketts, C., Kekana, V., Vezi, A., Basson, I., Magooa, P., Bhojraj-Sewpershad, N., de Gita, G., Maseko, V. and Lewis, D. (2013) P3.291 Associations of Chlamydia trachomatis Infection in Men and Women with Genital Discharge Syndromes in Johannesburg, South Africa. Sexually Transmitted Infections, 89, A239-A240.
    http://dx.doi.org/10.1136/sextrans-2013-051184.0746

  27. 27. Ohnishi, M., Golparian, D., Shimuta, K., Saika, T., Hoshina, S., Iwasaku, K., Nakayama, S.-I., Kitawaki, J. and Unemo, M. (2011) Is Neisseria gonorrhoeae Initiating a Future Era of Untreatable Gonorrhea? Detailed Characterization of the First Strain with High-Level Resistance to Ceftriaxone. Antimicrobial Agents and Chemotherapy, 55, 3538-3545.
    http://dx.doi.org/10.1128/AAC.00325-11

  28. 28. World Health Organization (2001) Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections: Overview and Estimates.

  29. 29. Venkatesh, K.K., van der Straten, A., Mayer, K.H., Blanchard, K., Ramjee, G., Lurie, M.N., Chipato, T., Padian, N.S. and de Bruyn, G. (2011) African Women Recently Infected With HIV-1 and HSV-2 Have Increased Risk of Acquiring Neisseria gonorrhoeae and Chlamydia trachomatis in the Methods for Improving Reproductive Health in Africa Trial. Sexually Transmitted Diseases, 38, 562-570.
    http://dx.doi.org/10.1097/OLQ.0b013e31820a8c2c

  30. 30. Mlisana, K., Naicker, N., Werner, L., Roberts, L., van Loggerenberg, F., Baxter, C., Passmore, J.-A.S., Grobler, A.C., Sturm, A.W. and Williamson, C. (2012) Symptomatic Vaginal Discharge Is a Poor Predictor of Sexually Transmitted Infections and Genital Tract Inflammation in High-Risk Women in South Africa. Journal of Infectious Diseases, 206, 6-14.
    http://dx.doi.org/10.1093/infdis/jis298

  31. 31. Abbai, N.S., Wand, H. and Ramjee, G. (2013) Sexually Transmitted Infections in Women Participating in a Biomedical Intervention Trial in Durban: Prevalence, Coinfections, and Risk Factors. Journal of Sexually Transmitted Diseases, 2013, Article ID: 358402.
    http://dx.doi.org/10.1155/2013/358402

  32. 32. Abbai, N.S., Moodley, P., Reddy, T., Zondi, T., Rambaran, S., Naidoo, K. and Ramjee, G. (2015) Clinical Evaluation of the OneStep Gonorrhea RapiCardTM InstaTest for Detection of Neisseria gonorrhoeae in Symptomatic Patients from KwaZulu-Natal, South Africa. Journal of Clinical Microbiology, 53, 1348-1350.
    http://dx.doi.org/10.1128/JCM.03603-14

  33. 33. Van Damme, L., Ramjee, G., Alary, M., Vuylsteke, B., Chandeying, V., Rees, H., Sirivongrangson, P., Tshibaka, L.M., Etticgne-Traoré, V. and Uaheowitchai, C. (2002) Effectiveness of COL-1492, a Nonoxynol-9 Vaginal Gel, on HIV-1 Transmission in Female Sex Workers: A Randomised Controlled Trial. The Lancet, 360, 971-977.
    http://dx.doi.org/10.1016/S0140-6736(02)11079-8

  34. 34. Johnson, L., Coetzee, D. and Dorrington, R. (2005) Sentinel Surveillance of Sexually Transmitted Infections in South Africa: A Review. Sexually Transmitted Infections, 81, 287-293.
    http://dx.doi.org/10.1136/sti.2004.013904

  35. 35. Pettifor, A.E., Kleinschmidt, I., Levin, J., Rees, H.V., MacPhail, C., Madikizela-Hlongwa, L., Vermaak, K., Napier, G., Stevens, W. and Padian, N.S. (2005) A Community-Based Study to Examine the Effect of a Youth HIV Prevention Intervention on Young People Aged 15 - 24 in South Africa: Results of the Baseline Survey. Tropical Medicine & International Health, 10, 971-980.
    http://dx.doi.org/10.1111/j.1365-3156.2005.01483.x

  36. 36. Das, A., Pathni, A.K., Narayanan, P., George, B., Morineau, G., Saidel, T., Prabhakar, P., Deshpande, G.R., Gangakhedkar, R. and Mehendale, S. (2013) High Rates of Reinfection and Incidence of Bacterial Sexually Transmitted Infections in a Cohort of Female Sex Workers from Two Indian Cities: Need for Different STI Control Strategies? Sexually Transmitted Infections, 89, 5-10.
    http://dx.doi.org/10.1136/sextrans-2012-050472

  37. 37. Da Ros, C.T. and da Silva Schmitt, C. (2008) Global Epidemiology of Sexually Transmitted Diseases. Asian Journal of Andrology, 10, 110-114.
    http://dx.doi.org/10.1111/j.1745-7262.2008.00367.x

  38. 38. Muzny, C.A. and Schwebke, J.R. (2013) The Clinical Spectrum of Trichomonas vaginalis Infection and Challenges to Management. Sexually Transmitted Infections, 89, 423-425.
    http://dx.doi.org/10.1136/sextrans-2012-050893

  39. 39. World Health Organization (2012) Global Incidence and Prevalence of Selected Curable Sexually Transmitted Infections—2008. WHO, Geneva.

  40. 40. Sturm, A.W., Wilkinson, D., Ndovela, N., Bowen, S. and Connolly, C. (1998) Pregnant Women as a Reservoir of Undetected Sexually Transmitted Diseases in Rural South Africa: Implications for Disease Control. American Journal of Public Health, 88, 1243-1245.
    http://dx.doi.org/10.2105/AJPH.88.8.1243

  41. 41. Watson-Jones, D., Changalucha, J., Gumodoka, B., Weiss, H., Rusizoka, M., Ndeki, L., Whitehouse, A., Balira, R., Todd, J. and Ngeleja, D. (2002) Syphilis in Pregnancy in Tanzania. I. Impact of Maternal Syphilis on Outcome of Pregnancy. Journal of Infectious Diseases, 186, 940-947.
    http://dx.doi.org/10.1086/342952

  42. 42. Buve, A., Weiss, H., Laga, M., Van Dyck, E., Musonda, R., Zekeng, L., Kahindo, M., Anagonou, S., Morison, L. and Robinson, N. (2001) The Epidemiology of Gonorrhoea, Chlamydial Infection and Syphilis in Four African Cities. AIDS, 15, S79-S88.
    http://dx.doi.org/10.1097/00002030-200108004-00009

  43. 43. Tenna, M., Aberra, G., Wondatir, N., Antoine, N. and Pierre, R.J. (2011) Prevalence of Trichomonas vaginalis Infections among Patients at Kiziba Refugee Camp and Centre Hospitalier Universitaire de Kigali (CHUK). KIST Journal of Science and Technology, 1, 31-38.

  44. 44. Naidoo, S. and Wand, H. (2013) Prevalence and Incidence of Trichomonas vaginalis Infections in Women Participating in a Clinical Trial in Durban, South Africa. Sexually Transmitted Infections, 89, 519-522.
    http://dx.doi.org/10.1136/sextrans-2012-050984

  45. 45. Apalata, T., Carr, W.H., Sturm, W.A., Longo-Mbenza, B. and Moodley, P. (2014) Determinants of Symptomatic Vulvovaginal Candidiasis among Human Immunodeficiency Virus Type 1 Infected Women in Rural Kwazulu-Natal, South Africa. Infectious Diseases in Obstetrics and Gynecology, 2014, Article ID: 387070.
    http://dx.doi.org/10.1155/2014/387070

  46. 46. Kapiga, S., Kelly, C., Weiss, S., Daley, T., Peterson, L., Leburg, C. and Ramjee, G. (2009) Risk Factors for Incidence of Sexually Transmitted Infections among Women in South Africa, Tanzania, and Zambia: Results from HPTN 055 Study. Sexually Transmitted Diseases, 36, 199-206.
    http://dx.doi.org/10.1097/OLQ.0b013e318191ba01

  47. 47. Etuketu, I.M., Mogaji, H., Alabi, O.M., Adeniran, A.A., Oluwole, A.S. and Ekpo, U.F. (2015) Prevalence and Risk Factors of Trichomonas vaginalis Infection among Pregnant Women Receiving Antenatal Care in Abeokuta, Nigeria. African Journal of Infectious Diseases, 9, 51-56.
    http://dx.doi.org/10.4314/ajid.v9i2.7

  48. 48. Crucitti, T., Jespers, V., Mulenga, C., Khondowe, S., Vandepitte, J. and Buvé, A. (2011) Non-Sexual Transmission of Trichomonas vaginalis in Adolescent Girls Attending School in Ndola, Zambia. PLoS ONE, 6, e16310.
    http://dx.doi.org/10.1371/journal.pone.0016310

  49. 49. Francis, S.C., Ao, T.T., Vanobberghen, F.M., Chilongani, J., Hashim, R., Andreasen, A., Watson-Jones, D., Changalucha, J., Kapiga, S. and Hayes, R.J. (2014) Epidemiology of Curable Sexually Transmitted Infections among Women at Increased Risk for HIV in Northwestern Tanzania: Inadequacy of Syndromic Management. PLoS ONE, 9, e101221.
    http://dx.doi.org/10.1371/journal.pone.0101221

  50. 50. Kuznik, A., Lamorde, M., Nyabigambo, A. and Manabe, Y.C. (2013) Antenatal Syphilis Screening Using Point-of-Care Testing in Sub-Saharan African Countries: A Cost-Effectiveness Analysis. PLoS Medicine, 10, e1001545.
    http://dx.doi.org/10.1371/journal.pmed.1001545

  51. 51. Newman, L., Kamb, M., Hawkes, S., Gomez, G., Say, L., Seuc, A. and Broutet, N. (2013) Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data. PLoS Medicine, 10, e1001396.
    http://dx.doi.org/10.1371/journal.pmed.1001396

  52. 52. Todd, J., Munguti, K., Grosskurth, H., Mngara, J., Changalucha, J., Mayaud, P., Mosha, F., Gavyole, A., Mabey, D. and Hayes, R. (2001) Risk Factors for Active Syphilis and TPHA Seroconversion in a Rural African Population. Sexually Transmitted Infections, 77, 37-45.
    http://dx.doi.org/10.1136/sti.77.1.37

  53. 53. Vandenhoudt, H.M., Langat, L., Menten, J., Odongo, F., Oswago, S., Luttah, G., Zeh, C., Crucitti, T., Laserson, K. and Vulule, J. (2013) Prevalence of HIV and Other Sexually Transmitted Infections among Female Sex Workers in Kisumu, Western Kenya, 1997 and 2008. PLoS ONE, 8, e54953.
    http://dx.doi.org/10.1371/journal.pone.0054953

  54. 54. Urassa, W.K., Kapiga, S.H., Msamanga, G.I., Antelman, G., Coley, J. and Fawzi, W.W. (2001) Risk Factors for Syphilis among HIV-1 Infected Pregnant Women in Dar es Salaam, Tanzania. African Journal of Reproductive Health, 54-62.
    http://dx.doi.org/10.2307/3583323

  55. 55. Nakku-Joloba, E., Kambugu, F., Wasubire, J., Kimeze, J., Salata, R., Albert, J.M., Rimm, A. and Whalen, C. (2015) Sero-Prevalence of Herpes Simplex Type 2 Virus (HSV-2) and HIV Infection in Kampala, Uganda. African Health Sciences, 14, 782-789.

  56. 56. De Baetselier, I., Menten, J., Cuylaerts, V., Ahmed, K., Deese, J., Van Damme, L. and Crucitti, T. (2015) Prevalence and Incidence Estimation of HSV-2 by Two IgG ELISA Methods among South African Women at High Risk of HIV. PLoS ONE, 10, e0120207.
    http://dx.doi.org/10.1371/journal.pone.0120207

  57. 57. Ramjee, G., Williams, B., Gouws, E., Van Dyck, E., Deken, B.D. and Karim, S.A. (2005) The Impact of Incident and Prevalent Herpes Simplex Virus-2 Infection on the Incidence of HIV-1 Infection among Commercial Sex Workers in South Africa. Journal of Acquired Immune Deficiency Syndromes, 39, 333-339.
    http://dx.doi.org/10.1097/01.qai.0000144445.44518.ea

  58. 58. Chohan, V., Baeten, J.M., Benki, S., Graham, S.M., Lavreys, L., Mandaliya, K., Ndinya-Achola, J.O., Jaoko, W., Overbaugh, J. and McClelland, R.S. (2009) A Prospective Study of Risk Factors for Herpes Simplex Virus Type 2 Acquisition among High-Risk HIV-1 Seronegative Women in Kenya. Sexually Transmitted Infections, 85, 489-492.
    Http://Dx.Doi.Org/10.1136/Sti.2009.036103

  59. 59. Kapiga, S.H., Ewings, F.M., Ao, T., Chilongani, J., Mongi, A., Baisley, K., Francis, S., Andreasen, A., Hashim, R. and Watson-Jones, D. (2013) The Epidemiology of HIV and HSV-2 Infections among Women Participating in Microbicide and Vaccine Feasibility Studies in Northern Tanzania. PLoS ONE, 8, e68825.
    http://dx.doi.org/10.1371/journal.pone.0068825

  60. 60. Masese, L., Baeten, J.M., Richardson, B.A., Bukusi, E., John-Stewart, G., Jaoko, W., Shafi, J., Kiarie, J. and McClelland, R.S. (2014) Incident Herpes Simplex Virus Type 2 Infection Increases the Risk of Subsequent Episodes of Bacterial Vaginosis. The Journal of Infectious Diseases, 209, 1023-1027.

  61. 61. Kenyon, C., Colebunders, R., Buve, A. and Hens, N. (2013) P3.065 Partner-Concurrency Associated with HSV-2 Infection in Young South Africans. Sexually Transmitted Infections, 89, A168-A168.
    http://dx.doi.org/10.1136/sextrans-2013-051184.0525

  62. 62. Abbai, N.S., Wand, H. and Ramjee, G. (2015) Socio-Demographic and Behavioural Characteristics Associated with HSV-2 Sero-Prevalence in High Risk Women in KwaZulu-Natal. BMC Research Notes, 8, 185.
    http://dx.doi.org/10.1186/s13104-015-1093-0

  63. 63. Weiss, H., Buve, A., Robinson, N., Van Dyck, E., Kahindo, M., Anagonou, S., Musonda, R., Zekeng, L., Morison, L. and Carael, M. (2001) The Epidemiology of HSV-2 Infection and Its Association with HIV Infection in Four Urban African Populations. AIDS, 15, S97-S108.
    http://dx.doi.org/10.1097/00002030-200108004-00011

  64. 64. Celum, C., Wald, A., Lingappa, J.R., Magaret, A.S., Wang, R.S., Mugo, N., Mujugira, A., Baeten, J.M., Mullins, J.I. and Hughes, J.P. (2010) Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2. New England Journal of Medicine, 362, 427-439.
    http://dx.doi.org/10.1056/NEJMoa0904849

  65. 65. Mugo, N., Dadabhai, S.S., Bunnell, R., Williamson, J., Bennett, E., Baya, I., Akinyi, N., Mohamed, I. and Kaiser, R. (2011) Prevalence of Herpes Simplex Virus Type 2 Infection, Human Immunodeficiency Virus/Herpes Simplex Virus Type 2 Coinfection, and Associated Risk Factors in a National, Population-Based Survey in Kenya. Sexually Transmitted Diseases, 38, 1059-1066.
    http://dx.doi.org/10.1097/olq.0b013e31822e60b6

  66. 66. Freeman, E.E., Weiss, H.A., Glynn, J.R., Cross, P.L., Whitworth, J.A. and Hayes, R.J. (2006) Herpes Simplex Virus 2 Infection Increases HIV Acquisition in Men and Women: Systematic Review and Meta-Analysis of Longitudinal Studies. AIDS, 20, 73-83.
    http://dx.doi.org/10.1097/01.aids.0000198081.09337.a7

  67. 67. Kirakoya-Samadoulougou, F., Nagot, N., Defer, M.-C., Yaro, S., Fao, P., Ilboudo, F., Langani, Y., Meda, N. and Robert, A. (2011) Epidemiology of Herpes Simplex Virus Type 2 Infection in Rural and Urban Burkina Faso. Sexually Transmitted Diseases, 38, 117-123.
    http://dx.doi.org/10.1097/OLQ.0b013e3181f0bef7

  68. 68. Glynn, J.R., Kayuni, N., Gondwe, L., Price, A.J. and Crampin, A.C. (2014) Earlier Menarche Is Associated with a Higher Prevalence of Herpes Simplex Type-2 (HSV-2) in Young Women in Rural Malawi. eLife, 3, e01604.
    http://dx.doi.org/10.7554/eLife.01604

  69. 69. Burd, E.M. (2003) Human Papillomavirus and Cervical Cancer. Clinical Microbiology Reviews, 16, 1-17.
    http://dx.doi.org/10.1128/CMR.16.1.1-17.2003

  70. 70. Allan, B., Marais, D.J., Hoffman, M., Shapiro, S. and Williamson, A.-L. (2008) Cervical Human Papillomavirus (HPV) Infection in South African Women: Implications for HPV Screening and Vaccine Strategies. Journal of Clinical Microbiology, 46, 740-742.
    http://dx.doi.org/10.1128/JCM.01981-07

  71. 71. Auvert, B., Marais, D., Lissouba, P., Zarca, K., Ramjee, G. and Williamson, A.-L. (2011) High-Risk Human Papillomavirus Is Associated with HIV Acquisition among South African Female Sex Workers. Infectious Diseases in Obstetrics and Gynecology, 2011.
    http://dx.doi.org/10.1155/2011/692012

  72. 72. World Health Organization (2009) Human Papillomavirus Vaccines. Weekly Epidemiological Record, 84, 117-132.
    http://www.who.int/wer/2009/wer8415.pdf

  73. 73. Tiggelaar, S.M., Lin, M.J., Viscidi, R.P., Ji, J. and Smith, J.S. (2012) Age-Specific Human Papillomavirus Antibody and Deoxyribonucleic Acid Prevalence: A Global Review. Journal of Adolescent Health, 50, 110-131.
    http://dx.doi.org/10.1016/j.jadohealth.2011.10.010

  74. 74. Smith, J.S., Melendy, A., Rana, R.K. and Pimenta, J.M. (2008) Age-Specific Prevalence of Infection with Human Papillomavirus in Females: A Global Review. Journal of Adolescent Health, 43, S5.e1-S5.e62.
    http://dx.doi.org/10.1016/j.jadohealth.2008.07.009

  75. 75. Ogembo, J.G., Manga, S., Nulah, K., Foglabenchi, L.H., Perlman, S., Wamai, R.G., Welty, T., Welty, E. and Tih, P. (2014) Achieving High Uptake of Human Papillomavirus Vaccine in Cameroon: Lessons Learned in Overcoming Challenges. Vaccine, 32, 4399-4403.
    http://dx.doi.org/10.1016/j.vaccine.2014.06.064

  76. 76. Piras, F., Piga, M., De Montis, A., Zannou, A., Minerba, L., Perra, M.T., Murtas, D., Atzori, M., Pittau, M. and Maxia, C. (2011) Prevalence of Human Papillomavirus Infection in Women in Benin, West Africa. Virology Journal, 8, 514.
    http://dx.doi.org/10.1186/1743-422X-8-514

  77. 77. Dempsey, A.F. (2008) Human Papillomavirus: The Usefulness of Risk Factors in Determining Who Should get Vaccinated. Reviews in Obstetrics and Gynecology, 1, 122-128.

  78. 78. Abaasa, A., Crook, A., Gafos, M., Anywaine, Z., Levin, J., Wandiembe, S., Nanoo, A., Nunn, A., McCormack, S., Hayes, R., et al. (2013) LONG-Term Consistent Use of a Vaginal Microbicide Gel among HIV-1 Sero-Discordant Couples in a Phase III Clinical Trial (MDP 301) in Rural South-West Uganda. Trials, 14, 33.
    http://dx.doi.org/10.1186/1745-6215-14-33

  79. 79. Reis Machado, J., da Silva, M.V., Cavellani, C.L., Reis, M., Monteiro, M.L.G., et al. (2014) Mucosal Immunity in the Female Genital Tract, HIV/AIDS. BioMed Research International, 2014, Article ID: 350195.
    http://dx.doi.org/10.1155/2014/350195

  80. 80. Kleppa, E., Ramsuran, V., Zulu, S., Karlsen, G.H., Bere, A., Passmore, J.-A.S., Ndhlovu, P., Lillebo, K., Holmen, S.D. and Onsrud, M. (2014) Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract. PLoS ONE, 9, e98593.
    http://dx.doi.org/10.1371/journal.pone.0098593

  81. 81. Reddy, B., Rastogi, S., Das, B., Salhan, S., Verma, S. and Mittal, A. (2004) Cytokine Expression Pattern in the Genital Tract of Chlamydia trachomatis Positive Infertile Women—Implication for T-Cell Responses. Clinical & Experimental Immunology, 137, 552-558.
    http://dx.doi.org/10.1111/j.1365-2249.2004.02564.x

  82. 82. Sperling, R., Kraus, T.A., Ding, J., Veretennikova, A., Lorde-Rollins, E., Singh, T., Lo, Y., Quayle, A.J. and Chang, T.L. (2013) Differential Profiles of Immune Mediators and in Vitro HIV Infectivity between Endocervical and Vaginal Secretions from Women with Chlamydia trachomatis Infection: A Pilot Study. Journal of Reproductive Immunology, 99, 80-87.
    http://dx.doi.org/10.1016/j.jri.2013.07.003

  83. 83. Masson, L., Mlisana, K., Little, F., Werner, L., Mkhize, N.N., Ronacher, K., Gamieldien, H., Williamson, C., Mckinnon, L.R. and Walzl, G. (2014) Defining Genital Tract Cytokine Signatures of Sexually Transmitted Infections and Bacterial Vaginosis in Women at High Risk of HIV infection: A Cross-Sectional Study. Sexually Transmitted Infections, 90, 580-587.
    http://dx.doi.org/10.1136/sextrans-2014-051601

  84. 84. Mitchell, C., Balkus, J.E., McKernan-Mullin, J., Cohn, S.E., Luque, A.E., Mwachari, C., Cohen, C.R., Coombs, R., Frenkel, L.M. and Hitti, J. (2013) Associations between Genital Tract Infections, Genital Tract Inflammation and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women. Journal of Acquired Immune Deficiency Syndromes, 62, 143-148.
    http://dx.doi.org/10.1097/QAI.0b013e318274577d

  85. 85. Cohen, C.R., Moscicki, A.-B. and Scott, M.E. (2010) Increased Levels of Immune Activation in the Genital Tract of Healthy Young Women from Sub-Saharan Africa. AIDS, 24, 2069-2074.
    http://dx.doi.org/10.1097/QAD.0b013e32833c323b

  86. 86. Kaul, R., Cohen, C.R., Chege, D., Yi, T.J., Tharao, W., McKinnon, L.R., Remis, R., Anzala, O. and Kimani, J. (2011) Biological Factors that May Contribute to Regional and Racial Disparities in HIV Prevalence. American Journal of Reproductive Immunology, 65, 317-324.
    http://dx.doi.org/10.1111/j.1600-0897.2010.00962.x

  87. 87. Wand, H. and Ramjee, G. (2015) Biological Impact of Recurrent Sexually Transmitted Infections on HIV Seroconversion among Women in South Africa: Results from Frailty Models. Journal of the International AIDS Society, 18, 19866.
    http://dx.doi.org/10.7448/IAS.18.1.19866

  88. 88. Stillwaggon, E. and Sawers, L. (2015) Rush to Judgment: The STI-Treatment Trials and HIV in Sub-Saharan Africa. Journal of the International AIDS Society, 18, 19844.
    http://dx.doi.org/10.7448/IAS.18.1.19844

  89. 89. Grosskurth, H., Todd, J., Mwijarubi, E., Mayaud, P., Nicoll, A., Newell, J., Mabey, D., Hayes, R., Mosha, F. and Senkoro, K. (1995) Impact of Improved Treatment of Sexually Transmitted Diseases on HIV Infection in Rural Tanzania: Randomised Controlled Trial. The Lancet, 346, 530-536.
    http://dx.doi.org/10.1016/S0140-6736(95)91380-7

  90. 90. Wawer, M.J., Sewankambo, N.K., Serwadda, D., Quinn, T.C., Kiwanuka, N., Li, C., Lutalo, T., Nalugoda, F., Gaydos, C.A. and Moulton, L.H. (1999) Control of Sexually Transmitted Diseases for AIDS Prevention in Uganda: A Randomised Community Trial. The Lancet, 353, 525-535.
    http://dx.doi.org/10.1016/S0140-6736(98)06439-3

  91. 91. Kamali, A., Quigley, M., Nakiyingi, J., Kinsman, J., Kengeya-Kayondo, J., Gopal, R., Ojwiya, A., Hughes, P., Carpenter, L. and Whitworth, J. (2003) Syndromic Management of Sexually-Transmitted Infections and Behaviour Change Interventions on Transmission of HIV-1 in Rural Uganda: A Community Randomised Trial. The Lancet, 361, 645-652.
    http://dx.doi.org/10.1016/S0140-6736(03)12598-6

  92. 92. Gregson, S., Adamson, S., Papaya, S., Mundondo, J., Nyamukapa, C.A., Mason, P.R., Garnett, G.P., Chandiwana, S.K., Foster, G. and Anderson, R.M. (2007) Impact and Process Evaluation of Integrated Community and Clinic-Based HIV-1 Control: A Cluster-Randomised Trial in Eastern Zimbabwe. PLoS Medicine, 4, e102.
    http://dx.doi.org/10.1371/journal.pmed.0040102

  93. 93. Mullick, S., Watson-Jones, D., Beksinska, M. and Mabey, D. (2005) Sexually Transmitted Infections in Pregnancy: Prevalence, Impact on Pregnancy Outcomes, and Approach to Treatment in Developing Countries. Sexually Transmitted Infections, 81, 294-302.
    http://dx.doi.org/10.1136/sti.2002.004077

  94. 94. Malla, N. and Goyal, K. (2012) Sexually Transmitted Infections: An Overview. In: Malla, N., Ed., Sexually Transmitted Infections, Chap. 1, InTech.
    http://dx.doi.org/10.5772/39380

  95. 95. Hoots, B.E., Peterman, T.A., Torrone, E.A., Weinstock, H., Meites, E. and Bolan, G.A. (2013) A Trich-y Question: Should Trichomonas vaginalis Infection be Reportable? Sex Transmitted Diseases, 40, 113-116.
    http://dx.doi.org/10.1097/OLQ.0b013e31827c08c3

  96. 96. Secor, W.E. (2012) Trichomonas vaginalis: Treatment Questions and Challenges. Expert Review of Anti-Infective Therapy, 10, 107.
    http://dx.doi.org/10.1586/eri.11.159

  97. 97. Becker, M., Stephen, J., Moses, S., Washington, R., Maclean, I., Cheang, M., Isac, S., Ramesh, B.M., Alary, M. and Blanchard, J. (2010) Etiology and Determinants of Sexually Transmitted Infections in Karnataka State, South India. Sexually Transmitted Diseases, 37, 159-164.
    http://dx.doi.org/10.1097/OLQ.0b013e3181bd1007

  98. 98. Moodley, P. and Sturm, A. (2004) Management of Vaginal Discharge Syndrome: How Effective Is Our Strategy? International Journal of Antimicrobial Agents, 24, 4-7.
    http://dx.doi.org/10.1016/j.ijantimicag.2004.02.003

  99. 99. Grosskurth, H., Gray, R., Hayes, R., Mabey, D. and Wawer, M. (2000) Control of Sexually Transmitted Diseases for HIV-1 Prevention: Understanding the Implications of the Mwanza and Rakai Trials. The Lancet, 355, 1981-1987.
    http://dx.doi.org/10.1016/S0140-6736(00)02336-9

  100. 100. Lewis, D.A. and Marumo, E. (2009) Revision of the National Guideline for First-Line Comprehensive Management and Control of Sexually Transmitted Infections: What’s New and Why? Southern African Journal of Epidemiology and Infection, 24, 6-9.

  101. 101. Somani, J., Bhullar, V.B., Workowski, K.A., Farshy, C.E. and Black, C.M. (2000) Multiple Drug-Resistant Chlamydia trachomatis Associated with Clinical Treatment failure. Journal of Infectious Diseases, 181, 1421-1427.
    http://dx.doi.org/10.1086/315372

  102. 102. Centers for Disease Control and Prevention (2008) Sexually Transmitted Diseases: Chlamydia—CDC Fact Sheet, Inc.

  103. 103. Hocking, J.S., Vodstrcil, L., Huston, W.M., Timms, P., Chen, M., Worthington, K., McIver, R. and Tabrizi, S.N. (2013) A Cohort Study of Chlamydia trachomatis Treatment Failure in Women: A Study Protocol. BMC Infectious Diseases, 13, 379.
    http://dx.doi.org/10.1186/1471-2334-13-379

  104. 104. Hafner, L.M., Wilson, D.P. and Timms, P. (2014) Development Status and Future Prospects for a Vaccine against Chlamydia trachomatis Infection. Vaccine, 32, 1563-1571.
    http://dx.doi.org/10.1016/j.vaccine.2013.08.020

  105. 105. Low, N., Unemo, M., Jensen, J.S., Breuer, J. and Stephenson, J.M. (2014) Molecular Diagnostics for Gonorrhoea: Implications for Antimicrobial Resistance and the Threat of Untreatable Gonorrhoea. PLoS Medicine, 11, e1001598.
    Http://Dx.Doi.Org/10.1371/Journal.Pmed.1001598

  106. 106. Lewis, D.A. and Lukehart, S.A. (2011) Antimicrobial Resistance in Neisseria gonorrhoeae and Treponema pallidum: Evolution, Therapeutic Challenges and the Need to Strengthen Global Surveillance. Sexually Transmitted Infections, 87, ii39-ii43.
    http://dx.doi.org/10.1136/sti.2010.047712

  107. 107. Moodley, P., Moodley, D. and Sturm, A.W. (2004) Ciprofloxacin Resistant Neisseria gonorrhoeae in South Africa. International Journal of Antimicrobial Agents, 24, 192-193.
    http://dx.doi.org/10.1016/j.ijantimicag.2004.04.003

  108. 108. Yokoi, S., Deguchi, T., Ozawa, T., Yasuda, M., Ito, S.-I., Kubota, Y., Tamaki, M. and Maeda, S.-I. (2007) Threat to Cefixime Treatment for Gonorrhea. Emerging Infectious Diseases, 13, 1275-1277.

  109. 109. Unemo, M., Golparian, D., Syversen, G., Vestrheim, D. and Moi, H. (2010) Two Cases of Verified Clinical Failures Using Internationally Recommended First-Line Cefixime for Gonorrhoea Treatment, Norway, 2010. Microscopy, 120, A121N.

  110. 110. Ison, C., Hussey, J., Sankar, K., Evans, J. and Alexander, S. (2011) Gonorrhoea Treatment Failures to Cefixime and Azithromycin in England, 2010. Eurosurveillance, 16, pii=19833.

  111. 111. Kirkcaldy, R.D., Bolan, G.A. and Wasserheit, J.N. (2013) CEphalosporin-Resistant Gonorrhea in North America. The Journal of the American Medical Association, 309, 185-187.
    http://dx.doi.org/10.1001/jama.2012.205107

  112. 112. Jerse, A.E., Bash, M.C. and Russell, M.W. (2014) Vaccines against Gonorrhea: Current Status and Future Challenges. Vaccine, 32, 1579-1587.
    http://dx.doi.org/10.1016/j.vaccine.2013.08.067

  113. 113. Andrei, G., Lisco, A., Vanpouille, C., Introini, A., Balestra, E., van den Oord, J., Cihlar, T., Perno, C.F., Snoeck, R. and Margolis, L. (2011) Topical Tenofovir, a Microbicide Effective against HIV, Inhibits Herpes Simplex Virus-2 Replication. Cell Host & Microbe, 10, 379-389.
    http://dx.doi.org/10.1016/j.chom.2011.08.015

  114. 114. Krawczyk, A., Arndt, M.A., Grosse-Hovest, L., Weichert, W., Giebel, B., Dittmer, U., Hengel, H., Jager, D., Schneweis, K.E. and Eis-Hubinger, A.M. (2013) Overcoming Drug-Resistant Herpes Simplex Virus (HSV) Infection by a Humanized Antibody. Proceedings of the National Academy of Sciences, 110, 6760-6765.
    http://dx.doi.org/10.1073/pnas.1220019110

  115. 115. Piret, J. and Boivin, G. (2011) Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management. Antimicrobial Agents and Chemotherapy, 55, 459-472.
    http://dx.doi.org/10.1128/AAC.00615-10

  116. 116. Bacon, T.H., Boon, R.J., Schultz, M. and Hodges-Savola, C. (2002) Surveillance for Antiviral-Agent-Resistant Herpes Simplex Virus in the General Population with Recurrent Herpes Labialis. Antimicrobial Agents and Chemotherapy, 46, 3042-3044.
    http://dx.doi.org/10.1128/AAC.46.9.3042-3044.2002

  117. 117. Bacon, T.H., Levin, M.J., Leary, J.J., Sarisky, R.T. and Sutton, D. (2003) Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral Therapy. Clinical Microbiology Reviews, 16, 114-128.
    http://dx.doi.org/10.1128/CMR.16.1.114-128.2003

  118. 118. Schwebke, J. R. and Barrientes, F.J. (2006) Prevalence of Trichomonas vaginalis Isolates with Resistance to Metronidazole and Tinidazole. Antimicrobial Agents and Chemotherapy, 50, 4209-4210.
    http://dx.doi.org/10.1128/AAC.00814-06

  119. 119. Rukasha, I., Ehlers, M. and Kock, M. (2013) P5.099 Metronidazole Antimicrobial Drug Resistance Testing of Trichomonas vaginalis Collected from Women Attending an Anti-Retroviral Clinic, Pretoria, South Africa. Sex Transmitted Infections, 89, A366-A366.
    http://dx.doi.org/10.1136/sextrans-2013-051184.1143

  120. 120. Straface, G., Selmin, A., Zanardo, V., De Santis, M., Ercoli, A. and Scambia, G. (2012) Herpes Simplex Virus Infection in Pregnancy. Infectious Diseases in Obstetrics and Gynecology, 2012, Article ID: 385697.
    http://dx.doi.org/10.1155/2012/385697

  121. 121. World Health Organization (2003) Guidelines for the Management of Sexually Transmitted Infections.

  122. 122. Holmes, K.K., Levine, R. and Weaver, M. (2004) Effectiveness of Condoms in Preventing Sexually Transmitted Infections. Bulletin of the World Health Organization, 82, 454-461.

  123. 123. Winer, R.L., Hughes, J.P., Feng, Q., O'Reilly, S., Kiviat, N.B., Holmes, K.K. and Koutsky, L.A. (2006) Condom Use and the Risk of Genital Human Papillomavirus Infection in Young Women. New England Journal of Medicine, 354, 2645-2654.
    http://dx.doi.org/10.1056/NEJMoa053284

  124. 124. Mash, R., Mash, B. and De Villiers, P. (2010) “Why Don’t You Just Use a Condom?”: Understanding the Motivational Tensions in the Minds of South African Women: Review Article. African Primary Health Care and Family Medicine, 2, 1-4.
    http://dx.doi.org/10.4102/phcfm.v2i1.79

  125. 125. Dochez, C., Bogers, J.J., Verhelst, R. and Rees, H. (2014) HPV Vaccines to Prevent Cervical Cancer and Genital Warts: An Update. Vaccine, 32, 1595-1601.
    http://dx.doi.org/10.1016/j.vaccine.2013.10.081

  126. 126. Adewole, I.F., Abauleth, Y.R., Adoubi, I., Amorissani, F., Anorlu, R.I., Awolude, O.A., Botha, H., Byamugisha, J.K., Cisse, L. and Diop, M. (2013) Consensus Recommendations for the Prevention of Cervical Cancer in Sub-Saharan Africa. Southern African Journal of Gynaecological Oncology, 5, 47-57.

  127. 127. Alam, N., Chamot, E., Vermund, S.H., Streatfield, K. and Kristensen, S. (2010) Partner Notification for Sexually Transmitted Infections in Developing Countries: A Systematic review. BMC Public Health, 10, 19.
    http://dx.doi.org/10.1186/1471-2458-10-19

  128. 128. Low, N., Broutet, N., Adu-Sarkodie, Y., Barton, P., Hossain, M. and Hawkes, S. (2006) Global Control of Sexually Transmitted Infections. The Lancet, 368, 2001-2016.
    http://dx.doi.org/10.1016/S0140-6736(06)69482-8

  129. 129. Mahmood, M. A. and Saniotis, A. (2011) Use of Syndromic Management Algorithm for Sexually Transmitted Infections and Reproductive Tract Infections Management in Community Settings in Karachi. Journal of the Pakistan Medical Association, 61, 453-457.

  130. 130. Alary, M., Gbenafa-Agossa, C., Aina, G., Ndour, M., Labbé, A., Fortin, D., et al. (2006) Evaluation of a Rapid Point-of-Care Test for the Detection of Gonococcal Infection among Female Sex Workers in Benin. Sexually Transmitted Infections, 82, v29-v32.
    http://dx.doi.org/10.1136/sti.2006.021865

NOTES

*Corresponding author.