42797
Sexually Transmitted Infections
In Developing Countries
Current concepts and strategies on improving STI
prevention, treatment, and control
ii
Table of Contents
Table of Contents...............................................................................................................iii
Acronyms and Abbreviations ............................................................................................ iv
Acknowledgements............................................................................................................. v
Executive Summary............................................................................................................ 1
I. The Global Burden of Sexually Transmitted Infections (STIs) and their
Consequences...................................................................................................................... 3
A. Overview: The Effects of STIs on Health and Development ................................. 3
B. STI Infections, Syndromes and Sequelae ............................................................... 4
C. Human and financial costs...................................................................................... 5
D. Prevention and Control of STIs .............................................................................. 6
E. Curative Treatment and Control of Transmission .................................................. 6
F. Primary Prevention of Chronic Infections and Sequelae of Viral STI ................... 7
II. STI Transmission Dynamics....................................................................................... 8
A. Determinants of STI Transmission......................................................................... 8
B. Biologic Factors Affecting STI Transmission........................................................ 9
C. Behavioral Factors Affecting STI Transmission .................................................. 10
D. Social and Environmental Factors Affecting STI Transmission .......................... 11
E. Special Case: The Interaction between HIV and Other STIs ............................... 11
III. STI Prevention & Control Strategies.................................................................... 12
A. The Basis for Effective STI control -- "Treatment is Prevention" ....................... 12
B. Supportive Elements for STI Prevention and Control.......................................... 21
C. Beyond Clinic-Based Care: Expanding STI Control Efforts............................... 26
D. Prioritizing Program Delivery Based on Resource Availability........................... 27
IV. Integration of Services.......................................................................................... 28
V. Future STI Prevention Initiatives and Opportunities................................................ 29
Annex A. Tables ............................................................................................................... 34
Annex B. Boxes ............................................................................................................... 41
Annex C. Website links .................................................................................................... 46
Annex D. References ....................................................................................................... 47
iii
Acronyms and Abbreviations
AIDS Acquired Immune Deficiency Syndrome
CDC U.S. Centers for Disease Control and Prevention
DALY Disability-adjusted life year
HBV Hepatitis B Vaccine
HIV Human Immunodeficiency Virus
HPV Human Papillomavirus
HSV-2 Herpes Simplex Virus-2
STD Sexually transmitted disease
STI Sexually transmitted infection
USD United States dollars
WHO World Health Organization
iv
Acknowledgements
This paper was prepared by a team from the U.S. Centers for Disease Control and
Prevention (CDC) and the World Bank. The team was led by Mary L. Kamb, Division of
STD Prevention, CDC and Eve Lackritz, Division of Reproductive Health, CDC. The
team consisted of professionals from CDC, including Jennifer Mark, Danielle B. Jackson,
Harriet L. Andrews, Cathleen M. Walsh, Thomas L. Gift, and Lesley C. Brooks; as well
as from the World Bank, including Rama Lakshminarayanan, Coordinator; Peter A.
Gaius-Obaseki, Junior Professional Officer; and Sadia Chowdhury, Senior Health
Specialist.
The team would like to express their gratitude to the reviewers at the World Bank for
their extensive comments and suggestions: F. Ayodeji Akala, Senior Public Health
Specialist; Pia Axemo, Senior Health Specialist; Shiyan Chao, Senior Health Economist;
Son Nam Nguyen, Senior Health Specialist; Kelechi Ohiri, Health Specialist; and Bert
Voetberg, Lead Health Specialist. The team is also grateful to Jessica St. John for
providing copyediting, formatting, and printing assistance.
The findings and conclusions in this report have not been formally disseminated by the
U.S. Centers for Disease Control and Prevention and should not be construed to represent
any agency determination or policy.
v
Executive Summary
The Global Burden of STIs on Health and Development
The global burden of sexually-transmitted infections (STIs) to health and development is often
overlooked as a public health priority. The majority of STIs worldwide are caused by eight infections:
syphilis, gonorrhea, chlamydia, trichomoniasis, genital herpes, hepatitis B virus (HBV), and human
papillomavirus (HPV). These infections, often silent and without symptoms, can result in serious or
fatal health consequences. Cervical cancer, caused by HPV, is the largest single cause of years of life
lost to cancer in the developing world and, because it affects women in their most productive years,
has a devastating effect on the well-being of families. Syphilis among pregnant women still results in
up to 1.5 million perinatal deaths each year. Damage to the fallopian tubes from gonorrhea and
chlamydia can lead to infertility, as well as tubal pregnancy, an important cause of maternal death in
developing countries. Hepatitis B, most frequently transmitted from mother-to-child in endemic areas,
can result in chronic infection, liver cancer and liver failure. Genital herpes and other genital ulcer
diseases increase risk of HIV transmission.
STIs are among the world's most common diseases, with an annual incidence exceeded only by
diarrheal diseases, malaria, and lower repiratory infections. The burden on the health care system and
healthcare expenditure is great. STIs, even without including HIV, are consistently among the most
common conditions leading to health care visits regardless of national resources. Due to their high
prevalence, particularly in developing country settings, STIs result in substantial productivity losses for
individuals and communities, particularly where the majority of the population is under 40 years of
age. In developing country settings, STIs are among the leading causes of disability adjusted life years
(DALYs) lost for women of reproductive age, exceeded only by maternal causes and HIV.
Effective, Affordable Solutions
The tragedy of the health and economic burden of STIs is that they are preventable and often treatable,
frequently with simple, inexpensive interventions. For example, stillbirths due to syphilis can be
prevented with routine screening of pregnant women and treatment with a single injection of penicillin.
A number of evidence-based and effective strategies have emerged and become widely accepted over
the past two decades:
Prevention through Treatment: Prompt identification and treatment of bacterial STIs remains a
cornerstone of STI control. Treating STIs reduces prevalence and breaks the chain of transmission in
the community, and is therefore the most effective form of prevention in the absence of a vaccine.
However, facility-based case management alone is not enough to control STIs. Core components of
STI control involves a series of interventions working together:
ˇ Clinic-based management of symptomatic STIs. Syndromic management has been
demonstrated to be effective in the absence of laboratory capacity.
ˇ Identification and treatment of sex partners
ˇ Screening asymptomatic persons (particularly women) at risk for adverse outcomes, such as
universal screening of pregnant women and routine cervical cancer screening
ˇ Targeted control measures among "core" high risk groups (e.g. sex workers) and populations
that "bridge" to the general population (e.g. clients of sex workers, truckers, and other mobile
populations).
1
Primary Prevention through Vaccines
Safe and effective vaccines against HBV and HPV hold the promise of eliminating a substantial
proportion of the world's STI-related cancers and chronic liver disease and have been added as a core
program element. Although inexpensive HBV vaccines are now widely available, they are still not
included in infant immunization schedules in some of the most affected countries.
Other Supporting Elements for Prevention and Control
In addition to the core components of STI prevention and control, six additional supporting elements
have proven important in ensuring the core programs can be effectively provided:
ˇ Leadership and advocacy to ensure an environment supporting STI control and prevention
ˇ STI surveillance to track burden of disease and track program impact
ˇ STI laboratory capacity that is sufficient to monitor critical diseases and support programs
ˇ Training around STI clinical management and prevention
ˇ Monitoring and evaluation of STI programs to assess progress and make needed changes
ˇ Community education around STI risks and prevention, especially important for youth
World Bank STI Technical Note
Although an increasingly large array of effective STI interventions exists, limited implementation and
quality of STI management occurs in some of the world's poorest nations. Prevention and control of
STIs can mitigate health costs, morbidity and mortality and help support poverty reduction efforts in
developing world settings, particularly among women, infants, and adolescents. STI control programs
are increasingly under-funded in many developing world settings. Some of the nations most affected
by STIs still lack the basic surveillance needed to establish burden of disease, monitor implementation
of programs and evaluate their impact. Many cost-effective strategies to prevent and control STIs are
inadequately implemented where they could provide the greatest good. In addition, newer strategies
that can prevent non-HIV morbidity and mortality need attention now to ensure systems are in place
for their adoption in the future. Better use of existing, effective STI prevention and control strategies,
including integration of systems when possible, could greatly assist many nations in reaching UN
Millennium Development Goals, particularly targets focusing on women, infants and children, and
youth of reproductive age.
This technical note was developed to provide World Bank technical staff a background in STI burden,
economic costs, evidenced-based STI programmatic interventions. New research findings and future
directions are also discussed, such as new point-of-care diagnostics, HSV treatment to prevent HIV
and male circumcision. Globally, the populations most vulnerable to STIs are those who are
disproportionately affected by other health and social issues: adolescents, pregnant women and their
unborn children, migrant populations and other economically or socially marginalized groups.
Accordingly, the technical note has emphasized STIs in these vulnerable populations, describing the
health and social consequences of STIs in women, adolescents and infants; how stigmatization and
gender inequities can affect health seeking and care and increase burden of disease; and the role that
STIs play on poverty and economic burden. Descriptions are provided about key STI prevention and
control strategies, available empiric data on their expected costs, and potential new strategies on the
horizon.
2
I. The Global Burden of Sexually Transmitted Infections (STIs) and their
Consequences
STIs are among the world's most common diseases, with an annual incidence exceeded only by
diarrheal diseases, malaria, and lower respiratory diseases. Due to their high prevalence, particularly in
developing settings, STIs result in substantial productivity losses for individuals and communities,
particularly where the majority of the population is under 40 years of age. In developing countries,
STIs are among the leading causes of disability-adjusted life years (DALYs) lost for women of
reproductive age.
A. Overview: The Effects of STIs on Health and Development1
Among the most common infectious diseases. Sexually transmitted infections are among the most
common of all infectious diseases. Every day nearly 1 million people acquire a new STI, and more
than 340 million new cases of curable STIs occur throughout the world each year. Adolescents and
young adults have the highest rates of curable STIs -- up to 1 in 20 adolescents develop a new STI each
year.
Infertility, tubal pregnancy, and maternal mortality. Untreated bacterial STIs in women result in
pelvic inflammatory disease in up to 40% of infections; and 1 in every 3 of these will result in
infertility. Tubal damage from STIs can lead to ectopic (tubal) pregnancy, the cause of up to 10% of
maternal mortality in settings with high STI prevalence. Chronic pelvic pain from untreated bacterial
STIs is an important cause of health care visits among women.
Infant blindness. Up to 4000 newborn babies become blind every year because of eye infections that
are attributable to untreated maternal STIs, and that could be easily prevented with topical infant eye
medications.
Perinatal deaths. Syphilis is one of the most important causes of adverse pregnancy outcomes
globally, estimated to account for up to 1,500,000 perinatal deaths each year equal or exceeding the
perinatal mortality associated with either HIV or malaria. In Africa and Latin America, 2 to 15% of all
pregnancies are in women with untreated syphilis. Infected women will experience an overall
perinatal mortality of 40% -- including stillborn infants and early neonatal deaths.
Inexpensive, cost-effective solutions. Syphilis screening and treatment (a penicillin injection) can cost
as little as 1 USD, and is among the most cost-effective all public health interventions -- but is still not
effectively applied in many nations. Universal syphilis screening and treatment in pregnant women
would prevent up to half a million perinatal deaths each year in Africa alone.
Chronic liver disease and death. Chronic infection with hepatitis B virus (HBV) is the most
important cause of disability and death from liver disease in developing world settings causing 1 in
40 deaths among adults globally each year. Most HBV is transmitted from mother to child at birth.
Existing HBV vaccine series cost 3 USD or less and, if provided to neonates, could prevent 30 to 70%
of all deaths related to liver cancers and cirrhosis among adults living in developing settings.
1Adopted from World Health Organization (WHO). 2006. Global Strategy for the Prevention and Control of Sexually
Transmitted Infections, 2006-2015. WHO: Geneva.
3
Cervical cancer and death. Cervical cancer is the most common cause of cancer mortality among
African women, and its frequency and progression are increased with HIV infection. New vaccines
against human papillomavirus (HPV) infection could stop the early death of approximately 240,000
women from cervical cancer every year in resource poor settings.
Effective strategies for prevention and treatment. Many viral STIs can be prevented with vaccines,
and most STIs (including some caused by viruses) can be prevented with male latex condoms. Many
common STIs can be cured with widely and affordable available antibiotic drugs, and symptoms and
infectiousness of certain viral STIs (e.g., HIV and genital herpes) can be ameliorated with antiviral
drugs.
B. STI Infections, Syndromes and Sequelae
Sexually transmitted infections (STIs) are among the world's most common diseases, with annual
incidence exceeded only by diarrheal diseases, malaria, and lower respiratory infections More than
thirty different bacterial, viral or parasitic agents are recognized as being transmitted sexually;
however, the majority of new STIs worldwide are caused by eight infections (syphilis, gonorrhea,
chlamydia, trichomoniasis, genital herpes, HIV, hepatitis B virus [HBV] and human papillomavirus
[HPV]). The World Health Organization (WHO) estimates that each year more than 340 million new
curable STIs occur in reproductive-aged men and women; this excludes the estimated 33 million new
cases of HIV as well as estimated 100 million plus infections caused by other viral STIs each year
(WHO, 2001). Excluding HIV, STIs and other reproductive tract infections (RTIs) account for a
substantial proportion of outpatient health care visits among adults of reproductive age, and in most
nations are ranked among the top five leading causes that individuals seek health care (Dallabetta et al.,
2006). In the United States, five of the 15 most commonly reported notifiable diseases are STIs
(gonorrhea, chlamydia, HIV, syphilis and hepatitis B) including the first and second most commonly
reported diseases, gonorrhea and chlamydia, respectively (Centers for Disease Control and Prevention,
2007).
In fact, reported STIs represent only the "tip of the iceberg" because most infections--typically more
than half of any specific diagnosis regardless of bacterial or viral etiology--are entirely asymptomatic
or (if symptoms exist) unrecognized (Adler, 1996; Kamb et al., 2000; Peterman et al., 2006). This is
especially true for women (Bolan et al., 1991; WHO, 2000; WHO, 2006a). Furthermore, adequate data
are not available in developing countries to even analyze reporting rates in those settings. Even when
symptoms exist, the social stigma associated with STIs in virtually every society contributes to their
under-detection. Shame, stigmatization or both lead many affected individuals to seek treatment
outside established health care systems, whether with traditional healers, self-treatment using
alternative or over-the-counter remedies, or through other avenues -- or to not seek treatment at all. In
almost all nations, more STIs are treated in the private than public health sector. Private (formal and
informal) providers have been found to have wider access and provide more confidential and less
judgmental services, but are also more likely to use unnecessary diagnostic tests, recommend outdated
or ineffective treatment regimens, and not treat sex partners thus leading to re-infection in the index
patient (Dallabetta et al., 2006). In most nations, a variety of challenges apply to both private and
public sector STI management (see Box 1) (Wilkinson, 1999; Connolly et al., 1999; Schneider et al.,
2001; Jacobs et al., 2004; Dallabetta et al., 2006; Nuwaha, 2006).
4
C. Human and financial costs
STIs impose costs on individuals and economies in several ways. Direct medical costs associated with
acute STI diagnosis and treatment can be substantial. A recent review of direct STI treatment costs in
low and middle income nations estimated the median cost for drugs alone for a single acute, bacterial
STI episode to be USD $2.62 (range, $0.05 to $35.23) -- more than three times the average daily
income for low income nations (Terris-Prestholt et al., 2006). Aside from acute care, the costs
associated with medical treatment for adverse outcomes related to STIs (e.g., treatment for infertility)
is substantial in industrialized nations, but has not been well documented in developing world settings.
STIs can also impose costs related to lost productivity due to STI morbidity and mortality (Table 1).
The STI-associated morbidity and mortality related to adverse pregnancy outcomes (stillbirth and early
neonatal deaths), reproductive morbidity and mortality (e.g., maternal deaths related to ectopic
pregnancy), anogenital cancers and chronic liver disease or cancer have been documented in
industrialized nations, but less so in low and middle-income settings. Similarly, the lost productivity
related to STIs themselves or unintended negative aspects of STI management (e.g., partner violence
associated with poorly implemented partner notification, divorce or family breakdown related to
infertility, depression related to stillbirth or neonatal death) are generally undocumented in developing
world settings. Another way that STIs could impose costs is through the impact of STI prevalence and
associated adverse outcomes on economic growth, whether locally or regionally. With the exception
of HIV, this STI cost has also not been well documented in either developed or developing world
settings.
Figure 1. Estimated Prevalence and Incidence of Curable STIs among Men and Women Age 15
44 Years, Globally and by Region (2001).
Each year, an estimated 340 million STI cases due to gonorrhea, chlamydia, syphilis,
and trichomonas occur; each case could be cured by commonly used antibiotic drugs.
Eastern Europe & Central Asia
18 million infections
Western Europe 11 per 100 adults
North America 16 million
14 million infections infections East Asia & Pacific
9 per 100 adults 8 per 100 adults 23 million infections
3 per 100 adults
Northern Africa & Middle East
10 million infections South & Southeast
6 per 100 adults Asia
150 million infections
16 per 100 adults
Latin America & the
Caribbean Sub-Saharan Africa
36 million infections 65 million infections Australasia
15 per 100 adults 25 per 100 adults 1 million infections
9 per 100 adults
Source: World Health Organization (WHO). 1995. An Overview of Selected Curable Sexually Transmitted Diseases,
Geneva: WHO, Global Programme on AIDS.
5
D. Prevention and Control of STIs
Strategies for prevention and control vary according to whether STIs can be cured with antibiotic drugs
or are caused by a virus and may result in long-term or even life-long infection (i.e., are non-curable).
The WHO estimation that 340 million new STIs occur globally each year among men and women aged
15 49 years refers specifically to curable STIs caused by common bacteria (i.e., gonorrhea,
chlamydia, syphilis, trichomoniasis) (Gerbase et al., 1998; WHO, 2001). If identified, each of these
infections can be effectively treated and cured using antibiotics that exist on the Essential Drug
formularies of most nations. However, if not appropriately treated or treated too late, these STIs can
cause a number of serious health consequences (Table 1). The most important consequences fall under
the general categories of reproductive morbidity and mortality (e.g., infertility), adverse pregnancy
outcomes (e.g., perinatal death, stillbirth), or enhanced acquisition or transmission of HIV infection
(e.g., from a genital ulcer or inflamed urethra or cervix) (Meheus, 1992; Gutman L.T., 1999; Watson-
Jones et al., 2002; Goyaux et al., 2003; WHO, 2006a). For a number of biologic and behavioral
reasons, curable STIs are most common in younger populations in their reproductive years, particularly
adolescents and young adults under age 24 (see Box 1).
Of all curable STIs, syphilis may cause the most substantial mortality and be the most easily
preventable disease. WHO estimates syphilis accounts for 750,000 to 1,500,000 perinatal deaths each
year (personal communication, Dr. George Schmid, WHO), and that prevalence rates among pregnant
women attending antenatal care clinics range from 2 to 10% in Latin America and 4 to 15% in Africa
(WHO, 2006a). Research studies indicate that 22 to 51% of all pregnancies among women with
untreated early syphilis will result in stillbirth, a further 14% of pregnancies result in neonatal death,
and that the least common (but most recognized) result of untreated maternal syphilis is congenital
syphilis in a live born infant (Ratnam et al., 1982; Aiken, 1992; McDermott et al., 1993; Watson-Jones
et al., 2002; WHO, 2006a).
E. Curative Treatment and Control of Transmission
Adverse health outcomes related to curable STIs are especially regrettable because they are
unnecessary; these infections can be effectively treated using affordable antibiotic drugs that are
already available in most nations (often as a single dose, thus able to be provided on-the-spot and
directly observed). Furthermore, most nations with intact health care infrastructure have already
demonstrated declines if not community control of syphilis and gonorrhea through use of straight-
forward public health control programs (e.g., effective STI management; asymptomatic screening of
vulnerable populations) (Berman and Kamb, 2007) (See Section IV). Curable STIs remain
problematic in settings lacking established health care systems, drug distribution systems, or adequate
surveillance (WHO, 2007) , and high prevalence of STIs such as syphilis as gonorrhea (particularly
among pregnant women) could be considered a marker of poor health care infrastructure. WHO
estimates that currently 80 to 90% of the global burden of curable STIs occurs in developing countries
(WHO, 2006b), with incidence and prevalence rates of these infections up to 20 times higher in
developing settings compared with Western Europe or North America (Adler, 1996), and with this gap
increasing over time (WHO, 2006b). As of 2006, the highest prevalence rates (i.e., population-based
burden) of curable STIs occurred in the sub-Saharan Africa nations, followed by Latin America and
the Caribbean, and South and Southeast Asia (Figure 1). However, because of large populations with
distributions skewed under 40 years, the largest numbers of curable STIs occurred in Asian nations
(Figures 1 and 2).
6
Figure 2. Global Estimates: Numbers and Incidence of Curable STIs per 100 Adults, by Region
Global Estimates of Curable STDs by Region
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F. Primary Prevention of Chronic Infections and Sequelae of Viral STI
The common viral STIs -- HIV, hepatitis B virus (HBV]) human papillomavirus (HPV), and herpes
simplex virus type-2 (HSV-2) -- are not included in the WHO global STI estimates, but are estimated
to account for the overwhelming majority of new (as well as prevalent) STIs (Agacfidan and Kohl,
1999). Viruses are not cured by antibiotics, and if not cleared by the body's immune system can lead
to latent infections, chronic infectiousness and/or serious sequelae, most notably primary cancers.
While not curable, two of the most important viral STIs -- HBV and HPV -- can now be prevented
through vaccination, and both HIV and HSV-2 can be treated with antiviral drugs that diminish their
infectiousness and long term complications.
HPV and Cervical Cancer: Common and Preventable
HPV is the most common STI. A recent U.S. study, using sensitive detection techniques, estimated
that 27% of sexually active women aged 14 to 59 years were infected with at least one HPV subtype
and other countries likely have similar prevalence. Most HPV infections are asymptomatic or cause
minimal morbidity (e.g., genital warts); however, certain HPV subtypes are established as the causal
agents of anogenital cancers including cervical, penile and anal carcinomas (zur Hausen, 1996). Two
carcinogenic HPV subtypes (16 and 18) are believed responsible for 70% of all cervical cancers and
80% to 90% of anal and penile cancers worldwide (Munoz et al., 2003; Daling et al., 2004; Daling et
al., 2005). For women, cervical cancer is the second most frequent cancer worldwide and the leading
cause of cancer deaths in the developing world, leading to up to 240,000 deaths per year (WHO,
2006a). In industrialized nations, cervical cancer has been associated with substantial morbidity but
decreasing mortality as cervical cancer screening increases. The enormous disparity in cervical cancer
7
deaths between industrialized and developing nations is largely attributed to availability of cervical
screening, standard-of-care in high-income (using Pap smears) and many moderate income (using
direct cervical visualization) nations. But in Africa it has been estimated that less than 5% of eligible
women have had cervical screening during the past 5 years (WHO, 2002a). HPV-related anogenital
cancers occur more frequently and progress more rapidly in HIV-infected individuals, and with the
advent of effective antiretroviral therapies against HIV have been an increasingly important cause of
HIV-related death. One of the most exciting new developments in STI research has been the
development of new HPV vaccines (discussed in Section V), which have the potential to essentially
eliminate cervical cancer and other anogenital cancers caused by HPV.
Prevention of Hepatitis B Virus and Resultant Chronic Liver Disease
HBV is another virus for which an effective vaccine exists (Section V). Common in developing world
settings, particularly in Asia, chronic HBV infection often results in serious, long-term complications
including primary liver cancer, cirrhosis, end stage liver disease and death (O'Farrell, 1999; Perz et al.,
2006). Primary liver cancer, called hepatocellular carcinoma, is the fifth leading cause of cancer death
in adults worldwide and third most common cancer in developing world settings (Pisani et al., 1999;
Parkin et al., 2001). Globally, at least half of all primary liver cancers are attributable to HBV,
although regional estimates vary (North America, 16%; Africa, 47%; Southeast Asia, 47%; Eastern
Mediterranean, 59%; East Asia, 65%) (Perz et al., 2006). Most HBV in developing settings is
transmitted from mother to child at birth, followed by parenteral transmission through tainted blood
products, organs, or medical or illicit drug injecting equipment; however, HBV is a sturdy virus that is
easily transmitted through unprotected sex (sex without a condom). Men who have sex with men are a
group at particularly high risk for sexual HBV transmission. Vaccination, preferably shortly after birth,
is the most cost-effective and practical approach to eliminating the adverse consequences of HBV.
Since the development of the first effective vaccine against HPV in the 1980s, several very low-cost
options have become available (See Section V). Serological tests can detect early cirrhosis and liver
cancers, but are not useful for disease prevention and are seldom available in developing world
settings.
Prevention of Genital Herpes Infections
Another common viral STI is HSV-2, the cause of genital herpes infection, which is often
asymptomatic but when associated with symptoms causes a genital ulcer syndrome. Genital herpes
has become the most common cause of the genital ulcer syndrome, in part due to program successes in
eliminating bacterial causes of genital ulcers (syphilis and chancroid) but also because of increasing
HIV prevalence in many countries. HSV and HIV are synergistic viruses: genital ulcers can enhance
HIV acquisition and transmission, and HIV results in increased shedding of HSV, thus more HSV
infections (WHO, 2006a). Treatment of genital herpes with specific antiviral agents can effectively
reduce the duration and frequency of ulcer episodes related to genital herpes, and thus reduce the
medical costs related to health care visits, the psychological costs of a chronic disease associated with
frequent outbreaks, as well as new infections in partners (Centers for Disease Control and Prevention,
2006).
II. STI Transmission Dynamics
A. Determinants of STI Transmission
As with other communicable diseases, the distribution of STIs in a given population is not static;
epidemics evolve through different phases characterized by changing patterns in the transmission (and
8
distribution) of STIs between and within various subpopulations (WHO, 2006a). Three factors are
believed to govern STI rates: (1) an agent's infectiousness (i.e., transmission efficiency per sexual
contact), (2) its duration of infectiousness, and (3) the rate of sex partner change among infected
persons. In early or well-controlled epidemics STIs are generally transmitted among high risk persons
with high STI prevalence and multiple and frequent changes in sex partners ("core groups"). As
epidemics evolve, STIs are spread from higher to lower risk individuals through individuals who have
sexual contact with both ("bridging groups") (WHO, 2006a) (Figure 3). Bridging groups vary from
society to society, but are often clients of sex workers or mobile men (e.g., truckers, miners, migrant
workers) who may transmit infections from higher risk partners to their wives or girlfriends. Thus,
targeted prevention programs aimed at core and bridging groups have been identified as important
priorities for interruption of transmission and disease control (see Table 2 in Annex A).
Figure 3: STI Transmission Dynamics in a Population (adapted from WHO 2006)
B. Biologic Factors Affecting STI Transmission
Individual biologic, behavioral, social and environmental factors can all determine a person's risk for
acquiring STIs (Dallabetta et al., 2006). Biologically, the "host's" anatomy, microbiology (e.g.,
vaginal flora), and hormonal and immunologic status may enhance likelihood of acquiring an STI.
Many STIs initially infect mucosal surfaces, such as the lining of the penile urethra in men, vaginal
walls and cervix in women, and oral pharynx and rectum. The relatively large surface area of the
female vagina confers particular risk for women for those STIs (e.g., syphilis, chancroid, trichomonas,
most viral STIs) that infect mucosal surfaces. Some STIs are attracted to specific target cells. For
example, the bacteria causing gonorrhea and chlamydia prefer the specialized columnar epithelial cells
lining of the female cervix. These cells are more exposed in young women, helping explain why
adolescent girls are at particular risk for these STIs. Viral STIs may have other targets; HIV
selectively attaches to specialized receptors common in the vaginal wall, rectal mucosa, and foreskin of
uncircumcised men. Other biologic factors can affect STI acquisition. Many STIs are inactivated by
acidic environments, and thus substances that increase vaginal pH (e.g., sperm, menstrual blood, or
chemical douching agents [liquids used to flush out the vaginal after sex or menstruation]) may
9
increase a woman's STI risk. The skin itself is an important protective barrier, and even small breaks
in the skin may enhance the likelihood of infection. Traumatic sex, caustic douching agents, or herbal
preparations used to dry out the vagina (practiced in some cultures to enhance sexual pleasure for
males) can all increase a woman's chance of acquiring STIs including HIV. Hormonal and
immunologic factors (e.g., pregnancy, use of oral contraceptives) can also enhance a woman's risk for
certain STIs.
C. Behavioral Factors Affecting STI Transmission
Not every encounter with an infected partner will automatically result in an STI. Some pathogens
appear to be highly infectious: For example, exposure to the bacteria causing gonorrhea results in
transmission to a sex partner in up to 50% of sexual exposures (i.e., 1 in 2 exposures). Other
pathogens, such as HIV, are much less infectious. In prospectively observed discordant couples (one
partner HIV infected and the other uninfected), only 0.002 to 0.0001% of sexual exposures led to a
new HIV infection (i.e., between 1 in 500 to 1 in 10,000 exposures) (Varghese et al., 2002). This
observation has supported the notion that HIV transmission or acquisition may require additional
"help" through means of an underlying co-infection (e.g., with an STI causing an ulcer or
inflammation), a break in the skin, a partner with a particularly high HIV viral load or some other
factor. In fact, laboratory and clinical research supports that new HIV infections are strongly
associated with STIs causing genital ulcers, and to a lesser extent those causing inflammatory urethral
and cervical responses.
Behavioral factors affecting STIs can be divided into personal risk behaviors and broader community
norms. Regarding personal risk behaviors, although abstinence is the only certain way to avoid STIs,
certain sexual practices (e.g., unprotected sex [without a condom], penetrative vaginal or anal sex) with
an infected partner are more likely to result in an STI or HIV than others (Varghese et al., 2002).
Furthermore, STIs are communicable diseases that, regardless of the riskiness of a particular sexual
practice, require an infected partner who is infectious enough to transmit the agent. Not surprisingly,
there is a direct relationship between higher number of sex partners and likelihood of acquiring an STI;
larger numbers of partners mean greater likelihood of contacting someone who is infected with an STI.
However, in communities with low STI prevalence, partner number may not be as strongly associated
with new STI as partner risk factors (i.e., a partner who has sex with other high risk people). Sex with
several low risk partners who themselves have sex with only a few low risk partners may be less risky
than sex with a single high risk partner (e.g., a sex worker, a client of a sex worker). As STI
prevalence decreases in a community, other partner characteristics such as prior STI, younger age and
lower education (perhaps resulting in fewer prior protective behaviors) appear to predict STI risk more
accurately than partner number (Peterman et al., 2000).
Mutually monogamy (both members of a partnership faithful to each other) is universally promoted as
an effective means of reducing risk for STIs including HIV, but obviously requires both partners to be
uninfected. However, STI status is not always known and may be difficult to ascertain in settings
where specific STI laboratory testing is not attainable or affordable. The effectiveness of mutual
monogamy also depends on both partners being faithful. This can be challenging in cultures that
expect women to be faithful to their husbands while allowing men to have overt or tacit access to other
partners (e.g., commercial sex workers). In such situations, relying on faithfulness alone may be very
risky for women, especially women who perceive themselves to have low STI and HIV risk and thus
not needing to employ protective measures such as negotiating condom use(Padian et al., 2007) (see
Box 3).
10
D. Social and Environmental Factors Affecting STI Transmission
While individual biologic and personal protective behaviors are important, the socio-cultural "macro-
environment" may affect STI patterns even more dramatically. Socio-demographic factors such as
younger age structures, sex ratio imbalances in either direction, urbanization and rural to urban
migration have all been observed to have large effects on STI prevalence (Dallabetta et al., 2006).
Younger age structures, by definition, means that a larger proportion of the population is susceptible to
STIs. Economic reforms, political unrest, natural disasters, or societal stigma around personal partner
choice have been observed to affect STIs as individuals (often young people) move from more rural
communities to cities in search of employment, safe shelter, or mates (Dallabetta et al., 2006). If
economic conditions require, some individuals generally young women -- may choose or be forced to
provide transactional sex (i.e., exchanging sex for goods in order to sustain themselves or their families
at home), and young men from rural areas may move to cities for further schooling, to obtain jobs or to
serve in the army. Urban environments providing mobile young adults access to larger numbers of
available sex partners (including higher risk partners), and thus to STIs. The movement away from
traditional communities and family structures can also be associated with a loosening of societal norms
around sex and increased STIs (Dallabetta et al., 2006). Although rural-to-urban migration may seem
to pose most STI risk for city-dwellers, rural communities can also be infected if young people
(typically young men) return home and transmit STIs to friends, fiancés and spouses. Paradoxically,
some countries have found higher HIV prevalence among rural than urban antenatal clinic attendees,
perhaps reflecting that rural women perceive themselves to be at lower STI risk or are less
knowledgeable about STIs and how to prevent them than their urban counterparts (O'neil et al., 2004;
Blanchard et al., 2005).
Literacy, educational levels and community health beliefs related to STIs (e.g., a community's
willingness to support dissemination of information about STI/HIV risk and preventive strategies) also
affect STI acquisition, particularly for women. Results from Demographic and Health Surveys (DHS)
conducted from 2000 through 2005 indicated that among 15-49 year olds, 22 to 61% of women in
Africa, 58 to 72% of women in Central Asia, and 34 to 73% of women in South and Southeast Asia did
not know that "people can protect themselves from contracting HIV by using condoms".
(Demographic Health Surveys (DHS), 2007) (Website: www.measuredhs.com). As recently as the late
1990s, surveys of female sex workers in India found that in 12 states fewer than half of participants
had ever heard of HIV/AIDS (Over, 1999). Aside from basic information, factors such as societal
stigma around STIs or certain other cultural practices (e.g., practice of male infant circumcision) can
affect prevalence of STI in a community (although in the case of circumcision, probably in opposite
directions.) (Male circumcision is discussed further in Section V). The HIV epidemic itself has had
an impact on the epidemiologic patterns of other STIs. In nations with high HIV prevalence, HIV may
enhance expression and transmission of certain STIs (most notably genital herpes) which enhance HIV
transmission and acquisition creating a vicious cycle (Paz-Bailey et al., 2006). Additionally, stigma
or fear around HIV may lead people with STI symptoms to avoid or delay health seeking, increasing
the chance that STI infections are missed and resulting in more long term consequences and further
spread of STIs in the community.
E. Special Case: The Interaction between HIV and Other STIs
Individuals infected with STIs causing genital ulcers (e.g., syphilis, chancroid, genital herpes) or
urethral or cervical inflammation (e.g., gonorrhea, chlamydia, trichomonas) are more susceptible to
11
acquiring HIV infection, probably because of disruption of mucosal integrity, increased prevalence of
HIV receptor cells or both (Wasserheit, 1992). Additionally, people co-infected with HIV and STIs
have been found to shed HIV virus more efficiently, and thus more likely to transmit HIV to an
uninfected partner. (Wasserheit, 1992; Fleming and Wasserheit, 1999). Furthermore, effective STI
treatment has been shown to reduce HIV viral shedding. Among high risk individuals such as female
sex workers, routine STI clinical services and condom promotion has been documented to reduce HIV
incidence or prevent HIV prevalence from increasing (Plummer et al., 1991; Wasserheit, 1992; Laga et
al., 1994; Levine et al., 1998). In the 1990s, one well-done community randomized trial in Mwanza,
Tanzania documented that communities receiving improved management of symptomatic STIs had
about 40% fewer new HIV infections compared with communities with typical STI management
supporting the benefit of high quality STD management for HIV prevention at the community level.
However, at least two subsequent, well-conducted community-level trials did not find the same HIV
prevention benefit. The lack of a similar effect in the later community level intervention trials has
caused experts to question whether a community-level HIV benefit to STD control could be expected
in all circumstances or all populations. A 2006 WHO Technical Consultation of experts concluded
that (1) the benefits of STD control for HIV prevention at the community level likely depends on
several factors including prevalence of curable STIs (i.e., syphilis, chancroid, gonorrhea), the coverage
of effective STI management, the phase of the HIV epidemic (with low level epidemics more
amenable to beneficial effect of STD control) and possibly other factors; (2) compelling evidence
supports that prompt identification and treatment of curable STIs among HIV-infected and HIV
susceptible individuals should be prioritized; and (3) effective STI management should include, in
addition to use of validated syndromic algorithms and availability of effective drugs in developing
settings, other prevention elements such as partner management, condom promotion, risk reduction
counseling or education, and HIV testing and counseling.
The association of the genital ulcer disease syndrome with HIV transmission has led many experts to
wonder whether HSV-2 viral therapy might reduce the likelihood of transmitting or acquiring HIV
infection (Weiss, 2004; Paz-Bailey et al., 2006). Multiple randomized trails of herpes therapy are
rigorously evaluating this theory. Several antiviral agents effective against genital herpes are widely
marketed, and some (e.g., acyclovir) are affordably priced for most nations. However, many nations
have not yet incorporated acyclovir into their national Essential Drug formularies (Paz-Bailey et al.,
2006; WHO, 2006a) and, given the well-documented benefit of this drug for genital herpes prevention,
and probably benefit for HIV prevention, this situation should be addressed particularly in nations
with high HIV prevalence. Similarly, the HPV vaccine may have implications for HIV transmission,
but research on this interaction is ongoing and is, to date, inconclusive.
III. STI Prevention & Control Strategies
A. The Basis for Effective STI control -- "Treatment is Prevention"
For communicable diseases such as STIs, case identification and treatment is the most effective form
of prevention in the absence of a vaccine. Treating STIs in individuals breaks the chain of
transmission, and thus reduces STI prevalence in the greater community (Parran, 1937). Many
industrialized nations have already effectively greatly reduced syphilis and gonorrhea prevalence
through a combination of basic ("core") program components, including:
(1) Clinic-based symptomatic STI case management. Effective case management assumes
etiologic or syndromic diagnosis of STIs, choice and availability of effective drug therapies,
12
education about compliance, counseling about STI risk reduction and provision of condoms
with instructions on their correct use (WHO, 2006a).
(2) Partner management. Because STIs are communicable diseases, sex partners must be treated
to eliminate chance for re-infection of the index patient. Partner management also helps break
the chain of STI transmission in the community (Centers for Disease Control and Prevention,
2006).
(3) Asymptomatic screening. Screening asymptomatic individuals (typically women) who are at
high risk for certain STIs reduces the most serious STI-related consequences (e.g., syphilis
screening among pregnant women to reduce adverse pregnancy outcomes, routine Pap smear
screening to reduce cervical cancer) (Berman and Kamb, 2007).
(4) Targeted STI control interventions. Interventions focused on core groups (e.g., sex workers)
or bridge populations (e.g., clients of sex workers, mobile men) prevent STI spread into the
general population and reduce subsequent morbidity (WHO, 2006a). Earlier STI control efforts
have been primarily aimed at curable STIs, but the development of vaccines against two
common viral STIs can substantially reduce the incidence and subsequent mortality of these
infections.
(5) Vaccines. Safe and effective vaccines against HBV and HPV, although not yet well
implemented into basic public health programs, hold the promise of eliminating a substantial
proportion of the world's STI-related cancers and chronic diseases.
Besides the five core components to STD prevention and control, six supportive elements have proven
important in ensuring the core program can be effectively provided (WHO, 2006a):
(1) Leadership and advocacy. When leaders are aware of the magnitude and importance of STIs
and associated morbidity, they can effectively advocate for high quality, sustainable programs.
(2) STI surveillance. Adequate surveillance is important to clarify burden of STIs and serious
STI-associated consequences to allow policy makers to make informed choices and to help
ensure sufficient quality of implementation of STI program elements. Surveillance can also
help monitor program successes and challenges.
(3) STI laboratory capacity. Sufficient although not necessarily excessive -- laboratory
capacity is needed to support local programs, including disease surveillance.
(4) Training. Appropriate training of health care providers (formal and informal) ensures core
STI prevention and control programs are provided efficiently and effectively.
(5) Monitoring and evaluation. Routine, periodic monitoring of program quality and evaluation
of program effectiveness through on-site visits, data review and operational research ensures
program quality, but requires effective program management.
(6) Community education. In addition to focus on facility-based STI management and treatment
and targeted interventions aimed at highly vulnerable populations, broad-based community
education around STIs including HIV, and how to prevent them, is important for primary
13
prevention. Education is particularly for adolescents and young adults as they have highest
STI rates, regardless of nation or community setting.
Figure 3. STI Prevention and Control:
Five core components and supportive elements
Leadership
and
Advocacy
STI Community
Surveillance Education
Asymptomatic Partner
Screening Management
Facility-based
STI Management
Targeted STI
Interventions Vaccines
STI Laboratory
Capacity Training
Monitoring
and
Evaluation
An in-depth description of the core program elements for STI prevention and control follows:
Core component #1: Effective STI Management
STI management is aimed at symptomatic individuals who seek health care, and thus is generally
facility-based whether provided in the public or private sector, or by formal or informal (e.g.,
traditional healers) providers. Case management based on etiologic diagnosis employs laboratory
diagnostic tests in combination with clinical presentation; management based on syndromic diagnosis
relies on patient symptoms, clinical presentation and examination. Regardless of diagnostic approach,
high quality STI management requires effective drug treatment, and is most successful if coupled with
prevention services including education on drug compliance, counseling on personal behavior change,
and provision of condoms and skills around correct and consistent condom use and, if appropriate,
contraception (WHO, 1991; Ryan, 1999; WHO, 2006a). Because HIV is behaviorally and biologically
linked to other STIs, any clinical encounter involving STI management is recommended to always
include offering of HIV testing and counseling (WHO, 2006b).
In many settings, reliable diagnostic tests are unaffordable or unavailable. Additionally, providers who
are not familiar with prevalent STI trends in the community may miss co-infections for which testing
was not done. Furthermore, the drug options preferred by health practitioners may be ineffective
against the organisms being treated, or may be unaffordable to patients. To address these problems, in
the early 1990s WHO began advocating that resource-limited settings encourage health providers to
use syndromic approaches for clinic-based STI/RTI management of symptomatic patients (Ryan, 1999;
Schmid et al., 2005; WHO, 2006a).
14
Syndromic Management Approaches. Syndromic approaches base treatment on patient-reported
symptoms and reported or observed clinical signs, using a series of flow charts (clinical algorithms)
that allow provision of standardized therapeutic regimens for specific syndromes. WHO recommends
that national STI control programs in developing countries incorporate syndromic flowcharts into their
STI/RTI management guidelines after validating and adapting them based on local epidemiology (Over
and Piot, 1993; Dallabetta et al., 2006; WHO, 2006a) . In most settings, there are benefits and
limitations to syndromic approaches (see Box 4).
Evaluation studies from low income settings support that syndromic approaches have been most
effective for management of certain syndromes, particularly genital ulcer syndrome in men and
women, urethritis and epididymitis in men and neonatatal conjunctivitis in infants (WHO, 2006).
Repeated cross-sectional studies in several nations with high STI prevalence indicate that bacterial
causes of genital ulcer syndrome (particularly chancroid, but also syphilis) have markedly declined in
parts of Africa over the past decade (WHO, 2006a). Although possibly related to other factors, these
observations suggest that adoption of syndromic management approaches can substantially reduce
prevalence of important bacterial STIs (especially those most highly associated with HIV transmission
and acquisition) in certain settings. With declining bacterial causes of genital ulcer syndrome, and
increasing prevalence of HSV-2, it will be important that national STI/HIV programs include acyclovir
or other HSV antiviral drug therapies routinely in their syndromic algorithms (WHO 2006 Report on
Technical Consultation on STI and HIV interaction).
Considerable debate has focused on the fact that syndromic approaches are less effective in managing
vaginitis, a common reason women seek health care, than other syndromes. Considered as an STI
control strategy, success of syndromic management is highly dependent on prevalence of inflammatory
STIs among women attending the primary care or family planning clinics and, not surprisingly, is least
effective in settings with lower prevalence of these STIs (as other factors can cause vaginitis). This
situation is particularly common in family planning and reproductive health clinics in many moderate
income settings, especially those with low HIV prevalence and in parts of Asia. On the other hand,
even when STI prevalence is low, syndromic approaches can be cost-effective and beneficial for
women if the primary objective is to treat all-cause vaginitis (caused by other reproductive tract
infections such as bacterial vaginosis or candidiasis) as well as STIs (Vuylsteke, 2004; WHO, 2006a).
Drug Availability and Antimicrobial Resistance. Effective STI management requires availability of
appropriate drugs, preferably those with acceptably low toxicity, for which microbial resistance is
unlikely to develop (or will be delayed), that can be administered orally preferably as a single dose
and that are not contraindicated in pregnant or lactating women (WHO, 2006b). An ongoing problem
for many nations is that the most desirable drugs are not included on the national essential drug lists.
While availability of STI drugs depends on a number of factors, the most immediately pressing is often
affordability, which often depends on national, regional and international considerations such as
patents, limited volume or limited competition, import duties and tariffs, and local taxes and mark-ups
for wholesaling. Local availability also depends on the efficient distribution of STI drugs and other
commodities to all levels of the health care system before product expiration dates. Drug distribution
is important for all diseases, but particularly important for STIs because of antibiotic resistance.
Worldwide, the effective treatment of gonorrhea, chancroid and to some extent syphilis has been
complicated by the spread of antimicrobial resistant strains. Currently, almost all gonorrhea strains
worldwide are resistant to first-line therapies including tetracycline, still often recommended by STI
providers. Furthermore, most gonorrhea strains in Asia and increasingly more in other developing
settings (including East Africa) are no longer susceptible to fluoroquinolone antibiotics. The loss of
this class of drugs has essentially eliminated the possibility of using oral antibiotics against gonorrhea
15
in many settings; communities must resort to injectable drugs such as ceftriaxone. When effective STI
drugs are not included on essential drug formularies, a "two tiered" system of drug availability often
results, with provision of less effective drugs at the peripheral health care levels and the most effective
(and generally more expensive drugs) only at the referral levels (Dallabetta et al., 2006; WHO, 2006a).
This, in turn, leads to an unacceptable rate of treatment failures, unnecessary referrals for patients,
further drug resistance and eroded confidence in the STI management program (WHO, 2006a).
Service Delivery. Effective STI management also requires symptomatic individuals have access to
sufficient quality services. Access to STI services is complex in most societies, as health seeking is a
function of attitudes around disease and sex as well as the availability, affordability and acceptability
of the services (Dallabetta et al., 2006). STIs are associated with substantial stigmatization and
prejudice, and tend to be viewed as "social diseases" that are dirty, shameful and somehow deserved.
This is a particularly difficult situation for many women (and infants) whose STI exposure is related to
partner rather than personal risk. STI service availability involves easy-to-reach locations, convenient
hours of operation, and providers trained in effective STI management approaches. Services must also
be affordable, and a number of personal and societal factors affect this. In some nations, public clinics
provide services free of charge, but individuals are required to pay for drugs. Prescribed drugs are
often expensive, exceeding many patients' daily income (Terris-Prestholt et al., 2006). Services must
also be acceptable to clients, but this can be affected by the shame and stigmatization that surrounds
STIs as well as judgmental or unsympathetic attitudes of some providers. Perceived empathy and
acceptance by service providers can have a profound impact on patients' opinions of services;
"(p)roviders should not scold" (Dallabetta et al., 2006). Factors such as privacy of setting and
confidentiality of services are also important to service acceptability. Adolescents and poorer or
marginalized groups (e.g., sex workers, men who have sex with men) most vulnerable to STIs who
may contribute most importantly to STI transmission dynamics in a community (Figure 3) may be least
likely to seek services in official settings. Effective STI control programs will ensure that acceptable
STI clinical services are available to these groups, often through specialized, targeted interventions
(See Core Component #4).
Core Component #2: Partner Management
Notifying partners that they have been exposed to an STI, and providing them (or encouraging they
seek) treatment is important to ensure that index patients are not re-infected with the STI. Partner
management also reduces further spread of the STI in the community. Although well recognized as a
core STI control strategy, effective partner management is not always implemented even in nations
with good resources. Effective strategies in developing settings with limited resources have not been
well studied.
Partner Management Can Be Difficult. Effective partner management can be difficult for several
reasons. Partner notification can be labor-intensive, costly and difficult (e.g., if public health outreach
is used). The social stigma surrounding STI diagnosis may lead patients to be reluctant to notify
partners or providers to recommend treatment. This may be particularly true for women who are in a
situation where partner violence may occur. Although research from the United States and Europe
suggests partner management does not lead to an overall increase in partner conflict or violence, this
may not be applicable to other societies or settings where cultural norms and gender power balances
differ. Many providers are reluctant to promote partner management without a clearly defined
etiologic diagnosis, as is the case for most syndromic STI management approaches. In certain settings
serving high risk patients who have anonymous or casual sexual encounters (e.g., sex workers, men
who have sex with men, itinerant workers), notifying partners can be impractical. Another reason that
16
partner management is poorly implemented is that established systematic approaches are often not
employed.
Effective Partner Management Approaches. At least three general partner management approaches
have been applied with apparent effectiveness in different parts of the world, provider notification
(e.g., through outreach), patient notification (e.g., giving partner(s) a card notifying about STI
exposure), and expedited partner treatment (i.e., patients provide partners effective STI drugs, or a
pharmacy card that allows partners to get drugs) (WHO, 2006b). Regardless of the approach
promoted, experts warn about the critical importance of avoiding coercion and observing
confidentiality, and about the potential importance of gender power imbalances (WHO, 2006a).
Strong evidence supporting one approach over the others in developing world settings does not yet
exist (WHO, 2006a), and this is an area where further research on best practices and cost-effectiveness
is warranted.
Core Component #3: Asymptomatic Screening
The objective of STI screening is to identify individuals who have asymptomatic or unrecognized STIs
that are associated with serious sequelae, and treat them before complications arise. Syphilis,
gonorrhea, chlamydia and HPV-related anogenital cancers are examples of STIs associated with
serious long term complications. European and North American nations have adopted asymptomatic
screening for most of these STIs, and in many cases have experienced notable reductions in the STIs
and their long term complications. Examples include maternal syphilis screening to reduce adverse
pregnancy outcomes, and Pap smear screening to reduce cervical cancers related to HPV. North
America and some European nations are also conducting chlamydia screening for young women in
order to reduce STI-related infertility; however, the success of this program is yet to be determined.
Asymptomatic screening appears to be most successful when attached to existing, facility-based
programs (e.g., as part of routine antenatal care, or part of routine family planning services).
For developing world settings, at least two situations exist in which asymptomatic screening may avert
substantial STI-related morbidity and mortality among women or infants, syphilis screening in
pregnant women and cervical cancer screening.
Syphilis screening in pregnant women. As noted earlier, maternal syphilis often leads to fetal loss,
stillbirth, neonatal death or debility, or congenital syphilis. Screening for pregnant women is a highly
cost-effective intervention (Table 2) supported by numerous research studies (Hira et al., 1990;
Jenniskens et al., 1995; Fonck et al., 2001; Walker et al., 2002; Terris-Prestholt et al., 2003; Peeling et
al., 2004; Vickerman et al., 2006a). Some experts have pointed out the irony of the widespread
adoption of other, more costly child-survival programs in settings where maternal syphilis still leads to
substantial morbidity and mortality (Dallabetta et al., 2006); Peeling et al; 2004). Although integration
of child survival programs to allow economies of scale seems to be an obvious solution, integrating
programs is not always simple. Most nations already recommend universal syphilis screening in
pregnant women; however, such screening is not always implemented or is done too late in pregnancy
to prevent adverse outcomes. Among the chief problems in the past has been the lack of affordable
and sufficiently accurate point-of-care diagnostic tests to allow infected women to be identified and
treated at the time of their clinic visit (and not lost to follow up). This situation has changed. Several
affordable, single antigen rapid syphilis test already exist, but are not yet widely used in settings where
they could make the greatest difference (Peeling et al., 2004). The WHO STD Diagnostic Initiative
(SDI) provides opportunities for nations to purchase rapid diagnostics such as these in bulk at very low
17
cost (www.who.int/std_diagnostics). At least two new dual antigen diagnostic tests are currently being
field-tested, and preliminary data suggests these will be reliable and affordable.
Cervical Cancer Screening. Cervical cancer continues to account for an estimated 250,000 deaths
annually of which most (80%) are in developing world settings. Cervical screening allows early
detection of cervical cancer precursors, and thus treatment of these lesions before they progress into
invasive cancers. Pap smear screening programs have resulted in precipitous drops in cervical cancer
in nations, most notably in Europe and North America. However, Pap smear screening programs are
costly, requiring trained cytopathologists to reliably read smears, intact transport services, high levels
of follow-up and health referral networks to ensure effective treatment of suspicious lesions before
they develop into cancers. In many developing world settings, none of these systems are in place.
While an estimated 50 million Pap smears are done each year in the United States alone, in poor
nations the majority of women do not have a single Pap smear during their lifetimes (Schmiedeskamp
and Kockler, 2006). In light of this problem, cancer experts are discussing the feasibility and potential
impact of more affordable screening options such as direct cervical visualization on cervical cancer in
developing world settings. Such options may have an important impact on disease, but they will still
require infrastructure that allows women to be referred for curative treatment. The recent development
of safe and effective vaccines against carcinogenic HPV subtypes has enormous potential for reducing
the incidence of cervical and other anogenital cancers but its impact in developing settings is still
unknown (See Core Component #5, Vaccines).
Core Component #4: Targeted STI Interventions for High Risk Populations
Targeted interventions refer to special STI prevention and treatment approaches directed toward
vulnerable populations, core groups, bridging groups or other sub-populations with high STI
prevalence, high rates of partner change or both and who do not access available STI management
services. Some of the groups most vulnerable to STIs are also those who may be highly stigmatized or
discriminated against (e.g., sex workers, men who have sex with men, sexually active adolescents).
These sub-populations may also avoid STI management provided at official health care systems,
because of real or perceived stigmatization, lack of trust in official systems, prior negative experiences
or other reasons (Dallabetta et al., 2006). Other vulnerable groups (e.g., prisoners, detained
populations, undocumented workers from other nations) do not have access to official health-care
systems. Some groups, such as men and women engaged in transactional sex, adolescents, itinerant
workers (miners, agricultural workers, truckers), refugees and other displaced populations may not
seek health care services because they do not recognize they are infected with STIs, or because they
lack the financial or other resources. The goal of targeted interventions is to expand the numbers of
STI-infected individuals who receive high quality STI management services (Dallabetta et al., 2006).
In most settings, and especially in low level epidemics where STI prevalence is concentrated among
certain core groups rather than the general population, targeting prevention, diagnosis and treatment
can have a strong impact on spread of STIs. The recent WHO Global Strategy for STI Control and
Prevention notes that targeted interventions should be a priority in settings where HIV and other STIs
are concentrated in high risk populations, although not to the exclusion of education and other
prevention and care services for the general population (WHO, 2006a).
Targeting Core Groups. It has been noted that "the labeling groups as `core' can produce stigma,
[however] the concept is intended to be epidemiological rather than moral or social" (Mayaud et al.,
1998b). In settings where core groups are not easily identifiable or approachable certain types of
targeting could further stigmatize them (e.g., street-based outreach for sex workers). One approach to
address this concern has been the use of peer-educators to conduct the outreach programs, either
18
providing services themselves, or referring their contacts to specialized services. Another approach
has been to develop specialized services (e.g., dedicated sex worker clinics; adolescent clinics). The
distinctive aspects of such targeted interventions may include dedicated, user-friendly clinical services,
with specially trained providers who provide professional and confidential services that are
conveniently located (perhaps even using mobile units).
Efficacy of Targeted Interventions. Evaluations studies have suggested mixed results about the
efficacy targeted STI intervention approaches; however, true evaluation can be difficult because of the
complexity of various approaches and the difficulties of ensuring the integrity and quality of the
interventions (Manhart and Holmes, 2005). An early example of an effective, targeted intervention for
sex workers was Thailand's 100% condom use program for brothel-based sex workers, which resulted
in significant reductions in STDs as well as HIV in the 1990s. The success of this intervention on
reduction of STIs and HIV may have been the result of the structural changes in laws and policies of
brothel-owners, as these were rigorously enforced by police, as opposed to individual behavior
changes among the sex workers. A number of other interventions aimed at sex workers, often using
rights-based approaches, have shown reductions in STDs and in some cases declines or maintenance of
low HIV prevalence (Vuylsteke et al., 2003).
Special Case of Adolescents. Adolescent women are at particularly high risk for STIs and are often
unable or unwilling to access official health care for a variety of reasons (see Box 2). The 2006 WHO
Strategy makes particular mention of the importance of developing and evaluating acceptability and
effectiveness of specialized clinical and prevention services for adolescents, perhaps incorporated into
other programs of interest (WHO, 2006a). Some recent examples of innovative services that seem
acceptable to many adolescents have utilized skills building interventions around condom use or
negotiating condom use with partners, sometimes using condom videos (Warner et al., 2006) or
internet interventions (Rietmeijer et al., 2003).
High Risk Men. Men whose work requires them to be on the move (e.g., truckers) or work away from
home (e.g., miners, migrant workers), or who are clients of sex workers are at high risk for contracting
STIs including HIV and also at risk for transmitting disease to regular sex partners. Many men do not
utilize public sector primary care systems for STI care, although they may seek treatment of symptoms
with private sector or with alternative providers (e.g., traditional healers, pharmacists) (see Box 5).
The recent WHO Global Strategy promotes "male involvement, male motivation and services for
men" as one of five new technologies for a strengthened response (WHO, 2006a). Some examples of
targeted interventions effective in providing STI prevention and treatment for high risk men include
programs that train pharmacists in quality STI management strategies and use of pre-packaged STD
kits. Facilities serving high risk men could also provide opportunities to support other prevention
strategies, including STI treatment for symptomatic men and STI screening (e.g., if men are provided
STI screening and treatment prior to surgery) as well as male circumcision. Additional prevention
services that could be included at these health facilities aimed at accessing high risk men include on-
site HIV testing and counseling, condom provision and education, specific behavior change
interventions aimed at risky sexual practices each of which would promote prevention and control of
STIs in addition to HIV prevention.
Men Who Have Sex with Men (MSM). MSM are at behavioral and biologic risk for other STIs as well
as HIV, but are often difficult to access for STI and HIV prevention or control. Depending on the
national or local context, cultural or societal norms or laws may affect men's ability to be open about
homosexual behavior, to access services or to socialize. MSM living in rural areas may be especially
isolated. Some men may have female as well as male partners, and may not self-identify as
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homosexual or bisexual. A number of targeted approaches have been effective in reaching MSM in
various settings, including models that use popular opinion leaders, peer educators or role models,
entertainment venues and (more recently) the internet (Mimiaga, 2006; Bowen et al., 2007).
HIV-Infected Persons. HIV-infected individuals have behavioral as well as biologic risk for other
STIs and, if co-infected with other STIs, are at high risk of transmitting HIV to others. Individuals
who are referred into HIV clinical care are an unusually accessible group because they are already
participating in the established health care delivery system; it is important not to miss any opportunity
to appropriately intervene. Several experts recommend all patients in HIV clinical care have initial
(and possibly periodic) screening for those STIs most associated with HIV transmission (e.g., syphilis,
gonorrhea, and in some settings chlamydia, trichomonas and HSV), and that women have cervical
cancer screening (Centers for Disease Control and Prevention, 2003).
Core Component #5: Preventive Vaccines
Vaccines provide primary prevention against the specific agents targeted, preventing any of its long
term sequelae and if widely enough practiced allowing the potential for reduction (or even
elimination) of the agent in the community. In the last 2 decades, successful vaccines have been
developed for HBV and HPV, and may be on the horizon for HSV-2.
HBV Vaccine. A HBV vaccine has been available since 1984, safety and efficacy rigorously
documented, and since that time inexpensive recombinant hepatitis B vaccines are increasingly
available in most of the world. Among those getting the full 3-dose series, about 95% of children and
90% of adults develop protective antibodies (Szmuness et al., 1980). The substantial morbidity and
mortality associated with chronic HBV, described earlier, provides a compelling economic rationale
for its widespread use particularly given that the full series costs as little as USD 3 (Table 2). WHO
has recommended since 1992 that all nations include HBV vaccine in their routine infant immunization
schedules; however, in 2003 global coverage of eligible infants was estimated at 42% or less (WHO,
2004). The long latent period between infection (during birth) and adverse health outcomes is
probably the critical factor leading to the underutilization of this important vaccine, and inclusion of
the vaccine as part of routine infant immunization schedules has been recommended of high priority
for any setting with substantially high HBV prevalence. HPV Vaccines. Two separate vaccine against
the HPV subtypes most commonly associated with cervical cancer (3-dose bivalent vaccine against 2
subtypes) or cervical cancer and genital warts (3-dose quadrivalent vaccine against 4 subtypes) have
recently been developed, and both rigorously studied and found to be safe and effective in preventing
persistent infections and cervical dysplasia. (Szmuness et al., 1980; Koutsky et al., 2002; Villa et al.,
2005). In 2006 the U.S. Advisory Committee on Immunization Practices recommended routine HPV
vaccination for females 11-12 years of age and catch up vaccination for females 13-26 years of age
who had not been vaccinated previously or who had not completed the full vaccine series, with other
industrialized nations expected to follow. A full 3-dose vaccine series is still expensive (~ $350), and
the utility of the vaccine among women with HIV-infection is still unclear. However, even expensive
interventions have the potential to be cost-effective or even cost-savings in nations with very high rates
of cervical cancer and where infrastructure for cervical cancer screening (also expensive) is not in
place because of substantial prevention to premature mortality among women (Table 2). As vaccine
prices fall, cost-effectiveness will improve in a number of settings and this intervention will need to be
seriously considered in STI control program.
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B. Supportive Elements for STI Prevention and Control
While not strictly core components, several additional elements should be in place to strengthen STI
prevention and control programs, such as adaptation of normative guidelines, training and information
networks, commodities logistics, laboratory support, surveillance and operations research.
Additionally, a supportive social and political environment, brought about by supportive leadership
and advocacy around STI prevention and control, although not strictly essential, goes far in ensuring
STI programs persist despite the prejudices associated with sex and associated disease. Six supportive
elements are:
Supportive Element #1: Leadership and Advocacy
Most societies have some prejudices associated with sex and associated disease. In many countries,
restrictive policies or laws may adversely affect STI/RTI prevention and control efforts (Dallabetta et
al., 2006). For example, some national or local policies restrict access of women or youth to services
or require spousal or parental permission for exams and treatment. Some limit access to preventive
measures such as condoms to adolescents or single women. In some settings, laws exist that prohibit
diagnosis and treatment of STIs by health care providers other than physicians or that encourage clinic-
based, laboratory-dependent or physician managed services exclusively, resulting in restrictive access
to STI services for some highly vulnerable populations (e.g., women, adolescents, sex workers)
(WHO, 2006a). Leaders may give low priority to STI control because they lack sufficient
understanding of the magnitude of disease burden, associated sequelae or potential economic
consequences related to STIs. Consequently, budget allocations for STI programs and drugs may be
low relative to other diseases, even in settings experiencing high STI prevalence and substantial
associated morbidity. Sector-wide approaches for donor aid to the whole health sector (rather than to
specific projects) allow health ministries to determine national priorities, but also mean that countries
which have accorded little importance to STI/RTIs in their health budgets in the past are likely to
continue to do this (WHO, 2006a). Additionally, although most nations have developed broad, multi-
sectoral responses to HIV, many have yet to develop formal strategies for the prevention and control of
other STIs and RTIs. Insufficient attention to STIs because of prejudice or lack of information can
also result in lack of a formalized, national control strategy, limited private (or even public) sector
commitment to STI care, inadequate training of providers, exclusion of effective antibiotics on
essential drug lists, or tariffs that make importation of essential drugs or commodities costly or difficult
(Dallabetta et al., 2006). Developing a supportive social and political environment for STI prevention
and control, despite the prejudices associated with sex and associated disease, can be an important
means of ensuring program success and sustainability.
Commitment and Advocacy from Leaders around Sexual Health. As one of its four Prime Objectives,
the most recent (2006) WHO Global Strategy for STI Prevention and Control calls for national leaders
to ensure that "policies, law and initiatives related to provision of STI care are non-stigmatizing and
gender-sensitive within the prevailing socio-cultural context" and enumerates as an "Essential Element
in the Response" a review of policies, laws and regulations regarding STI control to ensure that they
are non-punitive, non-coercive and contribute toward the aims of STI prevention and control services
(WHO, 2006a). In settings with high STI prevalence, commitment of policy makers helps provide a
foundation for a strong and effective national response. Coordination of representatives from related
health sectors (i.e., reproductive health and family planning, maternal child health, and HIV/AIDS
programs), along with stake-holders from public and private sectors within and outside the health
systems can help ensure a multi-sectoral response towards STI prevention and control that is strong
and sustainable. Ideally, these partners would be an integral part of a process developing a formal,
comprehensive national STI prevention and control strategy with clearly defined, time-phased goals
21
and objectives, and that outlines responsibilities for carrying out different elements of the strategy and
that covers all population groups for which interventions are required. Inclusion of all partners ensure
that health programs with similar interests or clients (e.g., STI, HIV, Reproductive Health, Family
Planning) promote mutually beneficial outcomes and develop program efficiencies, and that sectors
outside health (e.g., finance, trade, justice) understand how STIs affect societies and economies and
support the national program accordingly. Strong leadership and advocacy around sexual health also
allows a supportive environment that allows communities the ability to educate young people about
HIV and STIs and contraception, ways that that STIs and HIV are transmitted between partners, and
effective ways that they can protect themselves against STIs/HIV and undesired pregnancies, whether
through abstinence, delayed sexual debut, mutual monogamy or consistent and correct condom use.
Supportive Element #2: STI Surveillance
Surveillance systems allow clarification of disease burden, monitoring of STI trends useful in
evaluating program impact over time, and help in projecting resource needs. WHO's 2006 Global
Strategy for STI Prevention and Control indicates that many low-and moderate income nations lack
sufficient surveillance infrastructure, clearly defined procedures, human and other capacity, or funding
to effectively advocate for STI prevention and control or design and implement their national strategies
(WHO, 2006a). The 2006 Strategy notes that the basic components of STI surveillance (that ought to
be done in any country) include:
ˇ Case-reporting by syndrome or etiological report (per availability) disaggregated by age and sex.
Separate data among men and women, and among very young adults (15-24), other reproductive
aged adults (25-44) and mature adults (older than 44 years) are important in understanding the
dynamics of specific STI syndromes within the population and how well services are delivered and
organized. As possible, the formal and informal private sector (e.g., private physicians,
pharmacists) should be included in the reporting system (see Box 5). WHO notes that incentives to
encourage reporting, such as accreditation or other strategies may aid in this effort (WHO, 2006a).
ˇ Prevalence assessments and monitoring to identify and track the burden of symptomatic and
asymptomatic STIs in defined populations. Useful assessments can be carried out by means of
special surveys in targeted populations or by linking to routinely conducted (e.g., Demographic and
Health Surveys, HIV surveillance) or other special surveys. Over the past decade nucleic acid
amplification tests for STIs have become much less expensive, and use non-invasive samples (e.g.,
urine, self-administered vaginal swabs) that do not require difficult handling or transport
procedures can be collected even in remote field settings. Because these tests are highly sensitive
and specific, information from a relatively small samples from groups with high STD prevalence
could provide meaningful information on STI trends and help guide treatment protocols (WHO,
2006a)
ˇ Linking of related program data. Data from screening or case-finding programs conducted in
other health divisions (e.g., syphilis screening in ANC clinics, stillbirth or cancer surveillance by
hospitals, Pap smear screening in family planning clinics, HBV vaccine coverage by immunization
programs) would ideally be linked to STI program data. Formal collaborations between programs
ensure collection of critical program information (e.g., gestational age in maternal syphilis
screening) and sharing of mutually beneficial information.
ˇ STI etiologic studies. Periodic (e.g., every five years) assessment of STI etiologies (e.g., etiologies
of genital ulcers) using reliable and quality-controlled laboratory testing allows updating of
syndromic treatment algorithms or etiologic approaches recommended in national guidelines as
well as selection of appropriate antibiotics to be included on essential drug lists.
ˇ Selected antimicrobial resistance monitoring. Antimicrobial resistance monitoring for specific
pathogens (e.g., gonorrhea, chancroid) ensures appropriate antibiotic selections in national
22
guidelines, planning around drug procurement, adaptation of provider training and treatment
algorithms, and early warning about important trends that may affect prevalence and costs.
Depending on available resources, this can be done locally, nationally or regionally or even
international groups working on surveillance of antimicrobial resistant organisms.
Support Element #3. STI Laboratory Capacity
The importance of sufficient laboratory capacity to support core program components, even in low-
income settings, is often overlooked; however, as noted in the above discussion of surveillance, is
important in guiding effective national programs. Many settings have limited resources, or sufficiently
trained staff, to allow strong STI laboratory capacity, and the promotion of syndromic case
management approaches rather than diagnostic tests may have exacerbated this. Although extensive
laboratory capacity is not strictly necessary at all local levels, capacity should exist at the national level
to ensure quality of lower level services, support surveillance and ensure adequacy of treatment
protocols. This may entail periodic isolation and antimicrobial resistance testing of N. gonorrhoeae or
other pathogens. Reference facilities can provide quality control for lower level laboratories, and can
aid programs in diagnosis and treatment decisions with difficult cases unresponsive to first courses of
treatment at lower health care levels.
High quality laboratory systems require development of clearly defined procedures and appropriate
training for laboratory personnel. Internal quality control guidelines for specific laboratory procedures
must be established and adhered to, and laboratory participation in external quality assurance programs
is encouraged. Laboratories should be established and strengthened at regional or national elvels,
where feasible at local levels. Such a network of laboratories can work together to strengthen STI
services nationally and regionally.
Supportive Element #4: Training
Training ensures that adequate STI management (including diagnosis, treatment and prevention)
standards are met by all members of the health care team, whether they are clinicians, pharmacists,
laboratory personnel, receptionists or supervisors located in the public or private, official or even
informal sectors.
Beyond the Clinical Encounter. Adequate training does not involve only the biomedical aspects of STI
diagnosis, treatment and prevention; it includes education about how provider attitudes and beliefs and
social stigma affect STI prevalence, means of ensuring confidentiality of information and effective
ways of interaction that do not alienate the patients (FHI, 2001). Basic training is ideally provided to
every professional involved in any aspect of STI management taking into account the role and
responsibilities of the provider to ensure the training is pertinent. For example, if health care providers
delivering antenatal care or family planning services are expected to provide STI care in some
instances, their training should reflect this. Similarly if physicians are expected to provide prevention
interventions such as personalized risk reduction counseling, training should be included in these areas.
Training alternative providers (e.g., traditional healers) in risk reduction counseling, correct and
consistent condom use and partner notification strategies may be a way to expand service provision to
populations who do not access official health clinics. Training of supervisors is important to ensure
they are familiar with the programs under their oversight and also, as needed, to reorient skills to being
supportive and constructive in their feedback to providers, focused on constantly improving program
quality rather than judgmental and fault finding. Although basic training provides a foundation for
effective program provision, the need for refresher training or other continuing education should be
based on results of program monitoring, evaluation or both (Dallabetta et al., 2006).
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Innovative Training Models. Traditionally, training has involved on-site approaches. However,
innovative models such as distance and computer assisted learning may be helpful in some settings.
Professional associations can help promote training opportunities through continuing medical
education, conferences, journal articles and newsletters. Since training requires time away from
clinical work and involves substantial time and costs, some programs have tried to minimize costs by
bundling of training programs when appropriate (e.g. training on syndromic management,
confidentiality of services, respect, risk reduction counseling, condom demonstration).
Revising Professional Curricula and Other Strategies. Professional schools (e.g., medical, nursing,
pharmacy schools) and other educational institutions can play an important role in furthering an
effective national response against STIs. Syndromic STI/RTI management is often poorly
implemented by physicians who were trained in etiologic diagnosis using laboratory testing and thus
tend to view it as "unscientific." Inclusion of syndromic STI/RTI approaches in medical, nursing and
other professional school curricula, including their overall rationale and utility and the use of flow
charts, could go a long way in increasing its successful application by physicians and other clinical
providers. Pharmacists can also be educated to provide effective syndromic management (Green et al.,
1998; Garcia et al., 1998; Tuladhar et al., 1998). Inclusion of STI prevention and control strategies in
professional school curricula may also help support partner management, which is often poorly
understood by clinicians, and may help ensure that providers prescribe drugs that are available in the
community, affordable for the patient, require the fewest doses for the shortest possible period of time
and have the fewest side effects. (Dallabetta et al., 2006) Providing training on the burden of STIs and
other RTIs as well as HIV, their significant morbidity and potential prevention and control strategies as
a routine part of public health, laboratory and pharmacy school curricula is a structural intervention
that may have much greater sustainability than the current strategy of repeated on-site training for
clinicians involved in STI management. Incorporating routine, periodic updates on STI management
as part of professional recertification or licensing programs is another structural intervention that has
been successfully applied in some nations (Dallabetta et al., 2006) .
Supportive Element #5: Monitoring and Evaluation
Quality assurance monitoring and evaluation of ongoing programs, along with surveillance, are the
basis for establishing and sustaining STI control programs and keeping them relevant and effective
(Dallabetta et al., 2006). This assumes effective program management.
Program Management. Effective program management assumes establishment of local STI program
goals and objectives and development of needed protocols, standard performance targets or annual and
semiannual review sessions. Ideally, these should be consistent with national protocols.
Administrative structure outlined on paper, with clear lines of communication, supervision and
responsibility clarify roles and responsibilities and help support a common goal. Similarly, at local
levels, clearly defined procedures manuals should be developed for health service sites help clarifying
responsibilities and procedures and ensure programs are conducted as planned. Periodic (e.g.,
semiannual) reviews that link referral centers and local programs are generally more meaningful and
motivating to the health care team. Supportive supervision need not be confined to the public sector.
Linking the private sector, including pharmacists and other medicine dispensers as well as clinicians, is
helpful in supporting their engagement and commitment to providing good quality of services, and can
facilitate reporting to surveillance system (see Box 5). Engagement of the private sector can often be
achieved by including them in training opportunities (See Training).
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Program decentralization and privatization in many nations have led to challenges in developing
processes that ensure high quality care for the population in the private as well as public sector. Some
successful strategies to support program standards and quality have been identified, including:
ˇ National guidelines. Guidelines for STI case management can ideally be disseminated to all STI
care providers formal and informal, whether in the public or private sectors.
ˇ Licensing, certification and accreditation. This strategy helps maintain quality, safety and
geographical distribution of health-care systems and could apply to pharmaceutical and health-
insurance industries as well as health-service industry (WHO, 2006a). Professional associations
and other self-regulatory bodies whether function outside of or in partnership with government can
be an essential element of regulatory and quality control. Peer review and self-regulation (e.g.,
continuing education credits) can be useful, and may be particularly attractive to providers if linked
to financial incentives or access to better working conditions (WHO, 2006a).
ˇ Referral centers. Establishment of referral centers for complicated STI cases where diagnoses can
be reviewed and confirmed or enhanced improves overall program quality. Ideally, efficient
referral protocols should be included as part of standard management protocols, as drop outs of
referred patients are common. Special care should be taken not to send patients to long and
expensive journeys to centers that have little to offer the patient.
Program Monitoring. Several quality assurance monitoring strategies have been successfully applied
to promote the goals of specific STI program (or core components) and many are appropriate for
developing as well as developed world settings, such as:
ˇ Collecting limited, critical program indicators or "data for action," evaluating it routinely providing
timely, constructive feedback to lower levels: Local programs are more productive and goal-
focused when they are sure they understand the important outcomes on which they will be judged,
and are more open to suggestions if they also receive positive feedback for a job well done.
ˇ Direct observation and immediate feedback: Although expensive and time consuming for
managers, this is the only sure way of knowing that programs are implemented as conceived and is
essential information in understanding overall program strengths and weaknesses. WHO program
indicators PI-6 and PI-7 have been found to be excellent measures for evaluation, but are often not
implemented by managers because of lack of funding for travel or lack of management staff. Some
settings have had success using direct observation can also be done by simulated clients, staff
posing as clients who evaluate service delivery.
ˇ Ongoing training: Training is critical in ensuring providers are aware of up-to-date STI
management issues, drug therapies, and management strategies and is described under Support
Component #4.
ˇ Other quality assurance strategies: Some STI programs have employed other means of ensuring
high quality of program such as periodic client satisfaction surveys, case or "referral" conferences
in which providers discuss difficult (or routine) cases and provide feedback to each other.
Consultations and communication between health centers and referral centers by means of visits,
radio or telephone links provides new information and also facilitates professional trust and
confidence in the system and in peer professional networks.
Program Evaluation. Evaluating program strengths, weaknesses and impact is best done using a
combination of strategies:
ˇ Routinely collected data evaluating quality of STI programs and availability of essential STI drugs
and commodities should be used to evaluate program adequacy and plan future needs.
25
ˇ Special studies such as outbreak investigations for specific STIs (e.g., lymphogranuloma venereum
[LGV] in men who have sex with men, highly resistant gonorrhea) can provide important new
information.
ˇ Behavioral and STI biologic surveillance data collected (for example) as part of second generation
HIV surveillance can help clarify where prevention and control of other STIs is currently strong or
weak, and specific population vulnerabilities in the future.
ˇ The phase of the HIV epidemic locally has implications for STI priorities including surveillance
activities, and existing HIV systems can provide STI programs information on determinants of
HIV-STI epidemiology, the relationship of HIV to under-detection and underreporting of other
STIs and identification of important core groups and bridging populations as these populations
are likely similar for HIV and other STIs.
ˇ Special operational research studies are helpful to provide data on how programs, particularly core
components are working in reality, how well they are maintaining existing standards and
guidelines, and their impact on STI control and prevention in the community.
Supportive Element #6: Community Education
Educating communities, particularly young people at risk, about STIs and ways to prevent them is a
primary prevention strategy, and an example of a structural or environmental change aimed at disease
preventnion. Some noted experts believe that individual behavior change strategies for high risk
persons (e.g., the risk reduction counseling and condom promotion employed during routine STI
management or as part of targeted interventions for high risk groups) may not have as great an effect
on reducing disease prevalence in a community as community-wide behavior change strategies that
seek to change overall community norms (G. Rose). Such community-wide changes "shift the bell
curve" (disease risk in the entire population) to the left, bringing large benefits to the community,
although less benefit to individuals. Many examples of community education models exist, such as
social marketing campaigns and school-based educational strategies for children or adolescents.
C. Beyond Clinic-Based Care: Expanding STI Control Efforts
As noted earlier, for curable STIs, treatment is the most effective prevention method and thus high
quality clinic-based STI management is a cornerstone for STI control. Effective diagnosis and
treatment of curable STIs cures infections and minimizes adverse outcomes in the individual, and
reduces further spread of STIs and subsequent STI-related morbidity in the community. However,
case management alone has limitations that are graphically illustrated by an STI management model
that was developed using real data from rural African nations. Figure 5a describes STI prevalence in
the community, the series of steps needed to ensure effective treatment and the proportion of STIs that
are missed (not effectively treated) at each step.
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Figure 5a. Piot-Fransen Model of STI Prevalence and STI Case Management
The model illustrates that most individuals with STIs, even those with symptoms, never reach a health
unit that could provide effective diagnosis and treatment. Even among those who reach a health unit,
many are not treated correctly, do not use drugs correctly enough for cure, experience treatment
failure, or are re-infected because sex partners were not treated. These issues can be addressed,
however. Figure 5b shows the potential effects of (i) well conducted clinic-based case management,
which requires symptomatic persons seek and obtain effective treatment, (ii) the additional benefits
that asymptomatic screening, effective partner management and targeted outreach and community-
based programs can provide, (Hudson, 2001) and (iii) yet additional benefits primary prevention,
whether using an effective vaccine or widespread community education and promotion of abstinence
or safe sex practices including condom use. Clinic-based STI management alone will not control STIs
in a community. Rather, clinic-based management should be incorporated into an organized program
involving the other essential public health elements.
Figure 5b. Potential Effects of Additional Control Strategies used with STI Case Management
D. Prioritizing Program Delivery Based on Resource Availability (Annex A; Table 2)
Nations will vary in terms of the resources and personnel available and if resources are limited may
need to prioritize implementation of various elements of a national or local STI prevention and control
program. Table 2 in Annex A summarizes priority activities and the appropriate level of intervention
27
for STI prevention and control in countries with limited resources as well as those with more resources
available. Whenever possible, it is desirable for community-based programs to focus on local
epidemiology and thus encourage STI surveillance. Surveillance could employ case reporting of key
STIs (using either syndromic or etiologic reporting, based on local practices) and need not be extensive
(e.g., could use sentinel sites or sentinel populations) or excessive (e.g., could be conducted every three
to five years rather than annually).
Additionally, standard practices for STI management, whether using etiologic or syndromic diagnosis)
should be addressed early. Syndromic approaches were specifically developed to address settings with
limited resources, but must be locally validated in order to ensure drugs available and prescribed are
effective in treating prevalent STIs. Because of their links to HIV, prompt identification and treatment
of genital ulcers should be particularly promoted, and genital ulcer etiology evaluated (e.g., need to
include therapies for chancroid, HSV-2 in treatment algorithms). When resources are scarce,
interventions that take advantage of existing infrastructures are usually easiest to manage. Maternal
syphilis screening at the first-antenatal visit, with prompt treatment of positives, for pregnant women in
antenatal care is another limited and cost-effective intervention that for most resource-poor settings
should be universally implemented. Similarly, scaling up STI prevention and treatment programs for
HIV-infected persons in clinical care is an urgent priority as an STI-HIV co-infection is a marker of
enhanced likelihood of HIV transmission biologically as well as behaviorally.
For nations or local settings with stronger resources, other core or support STI program components
can be phased in as possible, including targeted interventions for high-risk and vulnerable populations,
age-appropriate sexual health education and services, promotion of partner treatment and prevention of
re-infection (which, while considered a core STI program component, can be difficult and costly to
implement) and scaling up of effective STI vaccines. The recent WHO Global Strategy for STI
Prevention and Control (2006) has recommended a strategy for prioritizing implementation of essential
STI prevention and control components in resource limited settings, recommending a series of
"Priority 1" strategies that should be implemented in all settings, regardless of resources, and "Priority
2" strategies that should be implemented if resources exist (Table 3) (WHO, 2006a).
IV. Integration of Services
The growing health and economic burden of STIs, HIV, and population growth in resource-poor
countries have led many organizations to reconsider traditional vertical approaches to health programs.
Men and women of reproductive age, even those living in stable couple relationships, are at risk for
HIV, STIs, and unintended pregnancies. For example in Uganda, 60% of persons found to be HIV-
positive in couples counseling and testing were in stable couple relationships with a seronegative
partner. Studies in Kenya, Zimbabwe, Haiti, and Tanzania found that more than half of the women
accessing HIV counseling and testing services did not want to get pregnant, and the majority were not
using a contraceptive method. The interaction of these sexually-transmitted conditions has fuelled an
interest in advancing integration of services at point-of-care to increase patient access, improve
efficiencies, reduce missed opportunities for prevention, and improve health outcomes. Though
vertical programs have the benefit of increased focus and expertise for a particular health issue, more
often men and women presenting for specific services leave with important health risks left
unaddressed. Integration of services holds the opportunity for HIV, STIs, and reproductive health
services to be delivered at a variety of entry points into healthcare systems, including HIV counseling
and testing centers, antenatal care, family planning, primary care services, and specialized STI
treatment or HIV clinical care.
28
Integration of HIV, STI, and reproductive health services has been identified as a priority in a number
of prominent forums. The 1994 International Conference on Population and Development in Cairo
released a consensus statement supporting comprehensive reproductive health services, including HIV
and STIs, with emphasis on the use of existing, mainstream, primary healthcare services of maternal
and child health and family planning services (www.iisd.ca/Cairo.html). USAID issued technical
guidance for field programs on family planning/HIV integration and has a website and workgroup
dedicated to integration issues and case studies. A high-level congress of the international donor
community held in Glion, Switzerland issued a call to action for integration of HIV and reproductive
health. The Center for Strategic and International Studies (CSIS) issued a document outlining strategic
opportunities for integration of reproductive health and HIV/AIDS programs in the U.S. President's
Emergency Plan for AIDS Relief (PEPFAR). A 2007 Technical Consultation on elimination of
congenital syphilis as a public health problem encouraged that congenital syphilis elimination be
approached through integration of the variety of antenatal services proven effective in reducing infant
and maternal morbidity, and advised against a vertical programs that might shift emphasis away from
other needed antenatal care components.
Other interactions exist between STIs, HIV, and reproductive health that lend themselves to a more
integrated approach:
HIV clinical care provides an important opportunity to screen for other STIs whose presence
represents biological and behavioral risk for HIV transmission, and to promote effective
contraceptive methods.
STI syndromic management should include promotion of HIV testing, risk reduction
counseling or education, and promotion of contraception when applicable.
Although STI and HIV screening among women attending family planning services may not be
cost-effective in low prevalence settings, in high prevalence settings, these services provide
access to sexually active women at risk;
Recent findings in three randomized trials indicate that there are substantial benefits to HIV
prevention through male circumcision. This new research will lead to expansion of
circumcision services for men and such services provide an excellent opportunity to promote
sexual health among men through screening for HIV and other STIs, counseling and education
on STIs, and effective contraceptive practices.
V. Future STI Prevention Initiatives and Opportunities
Several ongoing STI research areas hold promise for the future. In 2006 WHO released a new Global
Strategy for STI Prevention and Control which outlined recommended program focus for the next 10
years. In the Strategy, two global initiatives -- the elimination of bacterial causes of genital ulcer
disease and elimination of congenital syphilis as a public health problem were prioritized for action
now, given both are associated with serious health consequences that could be averted with generally
readily available and affordable interventions. Additionally, evaluation research for the WHO STI
Diagnostics Initiative continues to identify high quality and affordable rapid, point-of-care tests that
will support STI control even in settings with limited infrastructure and resources. Recent prevention
research around some biomedical interventions (e.g., HPV vaccines, male circumcision) has been
remarkably fruitful and exciting, other areas (e.g., vaginal microbicides) are proving more difficult in
identifying safe and effective interventions, and some areas (e.g., herpes treatment prevention of HIV
transmission and acquisition) have yet to be clarified but will in the next one to two years.
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A. WHO Global Strategy (2006)
The recently published WHO report, Global Strategy for the Prevention and Control of Sexually
Transmitted Infections: 2006-2015 Breaking the Chain of Transmission, developed using an
inclusive and broad consultative process within the WHO Secretariat and WHO Member States as well
as external partners, moves beyond earlier reports to emphasize the action steps needed for an
accelerated response to STI control (WHO, 2006a). Calling for improved sexual and reproductive
health as defined in the UN International Conference on Population and Development (1994), the
strategy has two broad components: technical and advocacy. The technical content of the report
emphasizes a public health approach to STI control focusing on delivery in primary health care
settings. New recommendations include the need for HIV and STI programs to integrate whenever
possible (e.g., recommendation of HIV testing at every STI clinical encounter), the importance of
focus on marginalized and vulnerable populations (e.g., adolescents) and the importance of monitoring
and evaluating program quality. The advocacy section provides recommendations to program
managers on mobilizing the political commitment necessary for an accelerated community response.
Recognizing that nations vary in their ability to respond to the strategy, action steps for provision of
interventions are prioritized, and national-level targets recommended (Table 3).
B. STI Diagnostics Initiative
The STI Diagnostics Initiative (SDI) is an externally funded program of diagnostic development,
partnering with UNICEF, the United Nations Development Programme, and the World Bank and
located in the WHO Special Programme for Research and Training in Tropical Diseases (TDR)
(http://www.who.int/std_diagnostics). The SDI's mission is to promote the development, evaluation
and application of diagnostic tests for STIs that are appropriate for use in primary health care settings
in developing world setting. In describing desire test capabilities, the Initiative uses the acronym
"ASSURED": tests should be affordable by those at risk for infection; sensitive (i.e., with few false
negatives); specific (i.e., with few false positives); user-friendly and simple to perform, ideally able to
done in four or fewer steps and with minimal training, rapid and robust to enable treatment at the first
visit and not requiring refrigerated storage, equipment-free and easy to collect, preferably with non-
invasive specimens such as urine or saliva, and with test results delivered at point-of-care to patients.
The current priorities for the SDI are the development and evaluation of rapid point-of-care tests for N
gonorrhoeae and C trachomatis in order to improve treatment among women presenting with vaginal
discharge and asymptomatic women at high risk (Mabey et al., 2001; Mabey et al., 2001; Mabey et al.,
2004). Also prioritized are rapid POC tests for syphilis to aid in screening antenatal women at risk for
congenital syphilis. Currently, the SDI website describes several high quality rapid treponemal tests for
syphilis which are available at affordable rates (several under 1 USD) for developing nations through a
WHO bulk purchasing mechanism. The initiative is also evaluating some new dual antigen,
treponemal plus non-treponemal tests for syphilis, which would allow identification of infectious
syphilis and add value to nations with current or recent high syphilis prevalence. SDI researchers
observe that their biggest current challenge is to ensuring that adequate-quality, rapid tests are
accessible to the developing country populations that need them most (Mabey et al., 2001).
C. Recent Prevention Research Findings
HPV Vaccine
30
One of the most exciting STI research developments in the past decade has been development of
vaccines against HPV, the largest single cause of years of life lost to cancer in the developing world
and a disease that, because it affects women in their most productive years, has a devastating effect on
the well-being of families (Agosti, 2007). A new quadrivalent HPV vaccine has been proven safe and
effective in preventing cervical cancer precursors associated with four common HPV subtypes,
including the two most common carcinogenic HPV subtypes worldwide (HPV 16/18) (Future II Study
Group, 2007). Earlier results from the bivalent vaccine (against HBV 16/18) demonstrated similar
efficacy. The burden of HPV-associated disease has been well characterized globally, allowing policy
makers from almost every nation to begin to consider the affordability and cost-effectiveness of HPV
vaccine relative to other budgetary needs. Experts point out that the effectiveness of this vaccine in the
field will require improved health systems for adolescents and environments that support government
health care and vaccine initiatives but this may be difficult given that programs targeting young
women may be misconstrued as attempts to control fertility. With a current cost of $350 USD for the
full 3 dose series, price is the greatest barrier to the introduction of the HPV, and subsidies will be
needed for any role out of this vaccine in developing world nations. The Global Alliance for Vaccines
and Immunization (GAVI Alliance) is a partnership of national ministries of health, WHO, the World
Bank, donor agencies such as the Bill and Melinda Gates Foundation, the vaccine industry, non-
governmental organizations and public health institutions that has provided technical assistance and
monetary resources for vaccines in low-income countries. Although HPV vaccine is not yet part of
GAVI's prioritized for support, it is hoped that with the help of this alliance HPV vaccines can begin
to be rolled out in those countries that would most benefit (Agosti and Goldie, 2007).
Adult male circumcision. Particularly compelling recent HIV/STI prevention research has been the
consistent findings from three randomized clinical trials in Africa (2006) that adult male circumcision
can reduce new HIV infections by approximately 40-60% (Auvert et al., 2005; Bailey et al., 2007;
Gray et al., 2007; US National Institutes of Health, 2006a; US National Institutes of Health, 2006b).
The multiple observational studies showing a benefit of circumcision for heterosexual men in reducing
their risk of HIV acquisition through sex with women were, clearly, correct. Communities are already
implementing or scaling up mechanisms that would allow safe and affordable adult circumcision for
interested men, often through use of specialized clinics.
As was the case with earlier observational studies, the circumcision trials also showed modest benefits
of circumcision in reducing risk for bacterial STIs (although not HSV-2). Preparatory work is already
underway to establish male circumcision programs as "male health" programs, in Africa. Adult men
seeking circumcision will be or at least perceive themselves to be at high risk for HIV (and through the
same risk, for other STIs), and thus such clinics have an opportunity of accessing the very men who are
most difficult to access in current primary care settings and who have tended to seek care outside
established health infrastructures. Integrated services could include STI and HIV screening, education
and counseling around STIs and risk reduction (including promotion of correct and consistent condom
use), contraception and other health issues (e.g., anemia, hypertension screening). Men identified as
HIV positive could be offered on enrollment into HIV clinical care programs.
Vaginal Microbicides. Microbicides, chemical substances developed for topical use inside vagina (or
rectum) to protect against HIV/STI, have been under study for several years. Although primarily
targeted at preventing HIV, an "ideal" microbicide would also protect against other STIs and would
help protect male partners as well as women (Minnis and Padian, 2005). Finding an effective agent
has proven elusive for several reasons. For one, ensuring safety of the microbicide in the doses
required to confer efficacy is problematic, and at candidate agents may actually confer risk if used in
31
certain formulations with very high doses. Additionally, evaluation can be difficult: ethically run
clinical trials require the control intervention to include strong promotion of all available effective
strategies, including provision and promotion of male latex condoms and risk reduction counseling.
Under study conditions, high risk "control" populations who are consistently provided prevention
support have often proven willing and able to apply these methods, reducing power to detect a
meaningful prevention benefit for any new microbicidal candidate. Consequently, while these trials
have greatly increased our knowledge about the risks and benefits of potential candidate agents and
about the potential for personal behavior change and condom use among high risk women sanctioned
to protect themselves as much as they can, as yet no microbicidal agent safe and effective against HIV
and other STIs is available. Several candidate agents are still under investigation, and efficacy studies
that are currently underway will be reporting results in the next several years (Alliance for Microbicide
Development, 2006). Acceptable female controlled methods to prevent against HIV/STI are important
because negotiation around use of the male latex condom is difficult for many women, particularly
women outside the sex industry whose greatest HIV/STI risk is through their regular partner. Other
methods besides microbicides are, such as the female condom (and possibly also diaphragms, cervical
caps and sponges although these appear to be most effective if used with a microbicidal agent) can
also be useful for some women and are as efficacious as the male condom in protecting against
HIV/STI (Minnis and Padian, 2005). Advantages to these barriers over the male condom are that they
can be inserted before and left in place for up to 24 hours after intercourse, and thus offer protection
for multiple coital acts, and they can be used without a partner's knowledge and may not require
negotiation. The female condom is substantially more expensive than male condoms (pennies),
however it is made out of a stronger material (polyurethane) that appears to be able to be safely reused
if appropriately washed dried and stored (WHO, 2002b). A number of small studies from around the
world have demonstrated reasonable acceptability of the female condom, especially among highly
vulnerable women such as commercial sex workers (Elias and Coggins, 2001) and STD clinic patients
(Artz et al., 2000).
Herpes treatment for HIV prevention. As noted earlier, clinical and research studies indicate that
herpes antiviral therapy suppresses genital HSV-2 shedding, and that there is a strong link between
HSV and HIV. Several clinical trials have recently or are currently investigating whether drugs that
suppress genital herpes infection can reduce HIV transmission, including one large multi-national trial;
and at least one large trial is evaluating whether HSV suppression can reduce HIV acquisition (Celum
et al., 2005; Paz-Bailey et al., 2007b) (Weiss, 2004). The largest study evaluating the impact of genital
herpes suppression on HIV infectiousness among discordant heterosexual couples is enrolling 3000
couples in which the HIV-infected partner is co-infected with HSV-2, hypothesizing that use of
standard doses of twice daily acyclovir by the co-infected partner will decrease the frequency and
extent of genital HIV shedding and thus, substantially reduce HIV transmission to the HIV-uninfected
sex partner. Trial results are expected within the next 12 24 months. A partner study is evaluating
effectiveness of similar, standard doses of acyclovir in preventing new HIV infection in HSV-infected,
heterosexual women and men who have sex with men. This study is enrolling a similar number of
participants, and is expected in 2010. Earlier, smaller trials have already reported a benefit of HSV
suppressive therapy on reducing HIV shedding in co-infected individuals, and that episodic therapy
reduces ulcer duration and HIV shedding from genital ulcers of symptomatic co-infected patients
(Nagot et al., 2007; Paz-Bailey et al., 2007a). HSV vaccine trials are also underway with efficacy
results expected in upcoming years.
32
33
Annex A. Tables: Table 1: Adverse Outcomes of STIs Occurring during Pregnancy and in Infants and Adult Women and Men
Adverse Pregnancy/Infant Outcomes
Syphilis Infant: Spontaneous abortion, stillbirth, preterm delivery, low infant birth weight, congenital syphilis
Chlamydia Maternal: Ectopic pregnancy, maternal death, preterm rupture of membranes;
Infant: Neonatal conjunctivitus, pneumonia, premature birth, low birth weight
Gonorrhea Maternal: Ectopic pregnancy, maternal death, preterm rupture of membranes;
Infant: Neonatal conjunctivitis, corneal scarring, blindness, premature birth, low infant birth weight
Trichomonas vaginalis Infant: Low infant birth weight, preterm delivery
Cytomegalovirus Infant: Primary infection of the newborn, hepatitis, sepsis, deafness, mental retardation, infant death
Genital Herpes Infection Infant: Primary infection of the newborn, hepatitis, sepsis, infant death
Human papillomavirus (HPV) Infant: Laryngeal papilloma
Hepatitis B virus (HBV) Maternal: Vertical transmission to infants;
Infant: Cirrhosis, end stage liver disease, primary liver cancer
Conditions in Adults
Chlamydia Women: Cervicitis, Bartholinitis, endometritis, salpingitis, pelvic inflammatory disease, chronic pelvic pain.
Men: Orchitis, epididymitis, perihepatitis, urethral stricture, prostatitis.
Both Men and Women: Infertility, proctitis, pharyngitis, Reiters syndrome, urethritis, perihepatitis (Fitz-Hugh-Curtis Syndrome),
enhanced HIV risk asymptomatic in up to 2/3 of cases, (LGV) ulcer or inguinal swelling
Gonorrhea Women: Cervicitis, Bartholinitis, endometritis, salpingitis, pelvic inflammatory disease, chronic pelvic pain
Men: Orchitis, epididymitis, urethral stricture, prostatitis
Both Men and Women: Infertility, proctitis, pharyngitis, Reiters syndrome, urethritis, perihepatitis (Fitz-Hugh-Curtis Syndrome),
disseminated gonococcal infection, enhanced HIV risk asymptomatic in 2/3 (women) and 1/3 (men) of cases.
Syphilis Both Men and Women: Primary ulcer (chancre), local adenopathy, skin rashes, condyloma lata, enhanced HIV risk; bone, cardiovascular
(e.g., aortic disease) and central nervous system disease (e.g., optic atrophy, tabes dorsalis), death
Chancroid Both Men and Women: Painful ulcers, inguinal adenitis, disfiguring lesions, tissue destruction, enhanced HIV risk
Trichomoniasis Women: Cervicitis, vaginitis, vaginal discharge, vulvar itching, endometritis, salpingitis, probably enhanced HIV risk
Men: Prostatitis, urethritis, urethral strictures, epididymitis, genital inflammation, infertility
Both Men and Women: Asymptomatic infection
Granuloma Inguinale (Donovanosis) Both Men and Women: Nodular swellings and ulcerative lesions of inguinal and anogenital areas
Other bacteria Women: Bacterial vaginosis, pelvic inflammatory disease, possibly enhanced HIV risk
(e.g., Mycoplasma, Ureaplasma) Men: Urethral discharge
Genital Herpes Infection Both Men and Women: Anogenital vesicular lesions and ulcerations, recurrent genital ulcers, cervicitis, proctitis, chronic pain, arthritis,
central nervous system involvement, hepatitis, meningitis, enhanced HIV risk
Human papillomavirus Women: Vulval and cervical warts, cervical dysplasia and carcinoma, vulval carcinoma
Men: Penile warts, penile carcinoma
Both Men and Women: Anal warts, anal carcinoma
Hepatitis B virus Both Men and Women: Acute hepatitis, liver cirrhosis, end stage liver disease, hepatocellular cancer
Kaposi's Sarcoma associated herpes Both Men and Women: Aggressive type of cancer in immunosuppressed persons
virus (HHV type 8)
HIV Both Men and Women: HIV-related disease, opportunistic infections, AIDS, death
Table 2: Operational Guidance for Implementation of Essential STI Prevention and Control
Activities in Resource-Limited Settings
Priority 1: Should be implemented in all nations
Priority 2: Should be implemented if resources exist
Priority 1 Activities and Indicators Suggested National-Level Targets2
[Level of Intervention]
1. Build on success. Scale up STI 1a). Proportion of primary point- 1a). 90% of primary point-of-care sites provide comprehensive STI
diagnosis and treatment (Use of-care sites providing care by 2015.
syndromic management where comprehensive case management
diagnostic resources are limited.) for symptomatic STIs. 1b). By 2015, 90% of women and men with STIs at health-care
facilities are appropriately diagnosed, treated and counselled.
[Any clinic providing family 1b). Proportion of patients with
planning and HIV services, STIs at selected health facilities
including STIs.] who are appropriately diagnosed,
treated and counselled according
to national guidelines.
2. Control congenital syphilis as a 2. Proportion of pregnant women 2a). More than 90% of first time antenatal care attendees aged 15-
step towards elimination. aged 15-24 years attending 24 years screened for syphilis.
antenatal clinics with a positive
[Antenatal and PMTCT clinics.] serology for syphilis. 2b). More than 90% of syphilis sero-positive women treated
adequately by 2015.
3. Scale up STI prevention 3. Proportion of HIV-positive 3a). Strategies and guidelines for HIV positive persons with STIs
strategies and programmes for patients with STIs who are given interventions in place by 2010.
HIV-positive persons. comprehensive care including
advice on condom use and 3b). 90% of primary point-of-care sites provide effective STI care
[Antenatal and PMTCT clinics or partner notification. for HIV infected persons.
any clinic where SRH and HIV
are linked.]
4. Upgrade STI surveillance 4a). Number of prevalence 4a). At least two rounds of prevalence surveys conducted by 2015.
within the context of second studies regularly conducted (at
generation HIV surveillance. sentinel sites or in sentinel 4b). Routine STI reporting established and sustained over at least 5
populations) every three to five consecutive years by 2015.
[MoH and National AIDS years.
Commissions.]
4b). Annual incidence of reported
STIs (syndromic or etiologic
reporting).
5. Control bacterial genital ulcer 5a). Proportion of confirmed 5a). Zero cases of chancroid identified in GUD patients by 2015.
disease (GUD).3 bacterial GUD cases among
patients with genital ulcerative 5b). Reduction to below two percent of positive syphilis serology
[Antenatal and HIV clinics.] diseases. among antenatal care attendees age 15-24 years.
5b). Percentage of pregnant
women aged 15-24 years
attending antenatal clinics with a
positive serology for syphilis.
6. Build on success. Implement 6a). Health needs identified and 6a). By 2010, health needs, policies, legislation and regulations
2National targets must be tailored to the country context, need, and availability of resources.
3Critical activity for pregnant women who are HIV-positive.
35
Priority 1 Activities and Indicators Suggested National-Level Targets2
[Level of Intervention]
targeted interventions in high-risk national plans for STI control, reviewed; plans in place and appropriately selected country-
and vulnerable populations. including HIV, for key high-risk specific targeted interventions implemented.
and vulnerable populations
developed and implemented. 6b). At least two rounds of prevalence surveys conducted among
groups with high-risk behaviour and among young people by 2015.
6b). Proportion of young people
(age 15-24 years) with STIs that
were detected during diagnostic
testing for STIs.
7. Implemented age-appropriate 7. Percentage of schools with at 7a). Review of policies and development of age-appropriate
comprehensive sexual health least one teacher who can provide training and information materials for schools completed by 2007.
education and services. life-skills-based HIV and other
STI prevention education. 7b). Increased number of teachers trained in participatory life-
[Ministry of Education and skills-based HIV education that includes other STIs by 2015.
Ministry of Health.]
8. Promote partner treatment and 8a). Proportion of patients with 8a). Plans and support materials for partner notification developed,
prevention of reinfection. STIs whose partner(s) are and health-care provider training in place by 2010.
referred for treatment.
[All levels of primary and 8b). Double the proportion of patients who bring in or provide
secondary care.] treatment to their partner(s).
36
Priority 2 Activities and Indicators Suggested National-Level Targets4
[Level of Intervention]
9. Build on success. Implement 6a). Health needs identified and 6a). By 2010, health needs, policies, legislation and regulations
targeted interventions in high-risk national plans for STI control, reviewed; plans in place and appropriately selected country-
and vulnerable populations. including HIV, for key high-risk specific targeted interventions implemented.
and vulnerable populations
developed and implemented. 6b). At least two rounds of prevalence surveys conducted
among groups with high-risk behaviour and among young
6b). Proportion of young people people by 2015.
(age 15-24 years) with STIs that
were detected during diagnostic
testing for STIs.
10. Support roll out of effective 9a). Policy and plans for 9a). Plans in place regarding vaccination for hepatitis B and
vaccines (HBV, HPV and universal vaccination for hepatitis HPV by 2008.
eventually HSV). B.
9b). Pilot vaccination programmes initiated and scaling up in
[Ministry of Health and Ministry of 9b). Plans and policy reviews and progress by 2010.
Finance.] strategies for implementation of
HPV and potential HS-2
vaccines.
11. Facilitate development and 10. Proportion of patients 10a). HIV testing and counselling available in all settings
implementation of universal opt-out assessed for STIs who are providing care for STIs by 2015.
voluntary counseling and testing for routinely counselled and offered
HIV among STI patients. confidential testing for HIV. 10b). Double the proportion of STI patients who receive
voluntary counseling and testing for HIV.
[Ministry of Health.]
4 National targets must be tailored to the country context, need, and availability of resources.
37
Table 3. Costs and Cost Benefits of Major STI Control Strategies5
STI Control Strategy, Country Unit cost Cost/ Cost/outcome Measure of health- Comment
Target Audience (Total treatment averted adjusted life year
Cost/N) saved
Indonesia
Syndromic STI Symptomatic males $3 per $3 per correctly 1998 USD
management 19-50 yrs male treated confirmed Not reported Not reported Lab confirmed GC/CT
(Djajakusumah et al., urethritis inflammatory STI prevalence= 75%
Symptomatic adults 1998) case
China $2 per male $3 per correctly 2002 USD
Symptomatic men urethritis treated confirmed Lab confirmed GC/CT
(age not reported) case inflammatory STI Not reported Not reported prevalence=69%
(Liu et al., 2003) $3 per GUD $14 per correctly Lab confimed GU
case treated confirmed (syphilis)
genital ulcer/STI prevalence=25%
Tanzania 1993 USD
Symptomatic men $10 per syndrome $218 per HIV Community STI
and women treated (genital ulcer infection averted $9 10 per DALY prevalence:
(discharge & ulcers) Not reported or discharge (based on study saved (based on HIV- Syphilis = 6%
(Mayaud et al., 1998) syndrome) of HIV 1 morbidity) HIV = 4%
incidence) Urethritis symptoms =
10%
South Africa
Male and female STI $2 per 1997 USD
patients (age not packet Estimated STI
reported)-- (drugs, info $7 per correctly prevalence among
pre-packaged sheet, treated confirmed Not reported Not reported women in region
syndromic STI condoms, inflammatory STI ( 1 STI) = 25%
packets partner card) HIV prevalence among
(Harrison et al., pregnant women in
2000) region = 30%
5All costs in US dollars unless otherwise noted; all costs include intervention and programmatic costs.
38
STI Control Strategy, Country Unit cost Cost/ Cost/outcome Measure of health- Comment
Target Audience (Total treatment averted adjusted life year
Cost/N) saved
Kenya $34 per woman
(Terris-Prestholt et al $2 per treated $280 per 2001 USD
Syphilis Screening in 2003 based on woman $22 per person perinatal $17 per DALY Maternal syphilis
pregnant women Jenniskens et al., screened treated (including outcome averted saved prevalence=7%
1995) partners)
Kenya $40 per woman $300 per 2001 USD
(Terris-Prestholt et al $1 per treated perinatal Maternal syphilis
2003 based on Fonck woman $26 per person outcome averted $19 per DALY saved prevalence=3%
et al., 2001) screened treated (including
partners)
Tanzania $1 per $20 per woman $187 per 2001 USD
(Terris-Prestholt et woman treated perinatal $11 per DALY Maternal syphilis
al., 2003) screened $15 per person saved prevalence=7%
treated (partners) outcome averted
Zambia $22 per woman $181 per 2001 USD
(Terris-Prestholt et al $1 per treated perinatal Maternal syphilis
2003 based on Hira et woman $12 per person outcome averted $11 per DALY saved prevalence=9%
al., 1990) screened treated (partners)
High Endemicity $30 - 40 per 1998 USD
Hepatitis B vaccine (Beutels 2001 based $3 per $4.2 carrier case Not reported Population Hep B
(3 dose series) for infants on Liu 1995) person averted prevalence = 70 - 90%
Medium Endemicity
(Beutels 2001 based 1998 USD
on Antonanzas 1995, Not reported $13 - 30 per person $385 - 2,108 per Not reported Population Hep B
Ginsberg 1996, infection averted prevalence = 20 - 55%
Garuz 1997)
Low Endemicity
(Beutels 2001 based $5,499 per QALY
on Margolis 1995, gained 1998 USD
Wiebe 1993, Szucs Not reported $31 - 127 per person $57 43,264 per Population Hep B
1998, Mangtani infection averted $5,615 14,271 per prevalence = 5 - 20%
1995, Fenn 1996, life-year gained
Williams 1996)
39
STI Control Strategy, Country Unit cost Cost/ Cost/outcome Measure of health- Comment
Target Audience (Total treatment averted adjusted life year
Cost/N) saved
France
Homosexual men (Beutels, 2001 based 1998 USD
(ages 15 40) on Kerleau et al Not reported $161 per vaccinated $ 765 per case Not reported Population Hep B
1995) person prevented prevalence =
HPV vaccine
(coupled with cytologic $20,600 per QALY 2002 USD
screening) United States $377 per Not reported gained (compared to HPV Prevalence =
(3 dose series) (Goldie et al., 2004) woman screening alone) (modeled)
Pre-adolescent girls 1% - 3% age<35 yrs
2000 International
Adolescent girls I$700 - I$9,600/YL
Brazil I$25 I$450 saved (not quality- Dollars (I$)
(Goldie, et al., 2007) per woman Not reported adjusted) compared HPV Prevalence =
to screening alone (modeled) 41.5% age
12-14 yrs
Targeted outreach $78 per DALY saved
(syndromic STI (full intervention) 2001 USD
management, condoms, and South Africa Prevalence HIV= 45% -
periodic presumptive (Vickerman et al., $44 per $102 per syndrome $2,093 per HIV $31 per DALY saved 54%
treatment) 2006) clinic visit treated infection averted (incremental cost of
adding periodic Prevalence CT or GC=
39%
Female sex workers presumptive
treatment to others
40
Annex B. Boxes
Box 1: Benefits and Challenges to Private and Public Sector STI Management
Private Sector Public Sector
Benefits - Much wider access - Easier provision of standardized
- Greater confidentiality accountable services (e.g., syndromic)
- Less judgmental attitudes - Greater opportunity for oversight
- More highly valued by clients, - Lower costs to patient (e.g., subsidized)
including at-risk populations - Greater likelihood of including prevention
- More respectful provider attitudes elements (counseling, condoms, HIV test)
- More efficient services - Partner treatment more likely
Challenges - Higher costs related to testing - Limited access, long waiting times
- Greater likelihood of inadequate - Lower acceptability, especially for men and
reatment choices vulnerable groups (e.g., adolescents, sex workers)
- Partner treatment less likely - Provider tendency to scold patients,
- Lower accountability disrespectful attitudes towards clients
- Quality of care may depend on - Quality dependent on intact health care system
client's ability to pay (e.g., supplies depend on distribution system)
Based on operational research studies from Uganda, Ghana, South Africa and India. (Schneider, 2001; Jacobs 2005;
Conolly 1999; Wilkinson 1999; Nuwaha, 2006; Dallabetta, 2006).
41
Box 2: Why Adolescents are at Particularly High Risk for STIs
In many developing countries, more than half of the population is 15 years old or younger, and in some
countries three quarters of all people are younger than age of 25. Throughout the world, adolescents and young
adults under age 25 have the highest STI rates. Each year 1 in every 20 adolescents will develop a new STI.
Why are young people at such high STI risk?
ˇ Adolescents and young adults are more likely to have multiple partners (sequential or concurrent
partnerships) rather than long-term relationships. Higher partner numbers and concurrent
partnerships increase the chance of exposure to an STI. Adolescents are more likely to choose sex
partners who are also adolescents and who may already have an STI (Dallabetta et al., 2006).
ˇ Early age at first sex increases the chance of exposure to an STI. Biologically, young women appear
to be at even greater risk than young men.
ˇ Many young people have difficulty using effective preventive strategies. They may be unable to
refuse sex with partners, or unaware that condoms are effective against STDs including HIV if used
consistently and correctly. Adolescents are less able to negotiate with partners about using condoms
and often lack experience in using them correctly. They may also lack the resources to buy
condoms.
ˇ Adolescents have less access to healthcare and fewer resources for health services or effective
treatment. Some communities or health facilities have restrictive policies requiring parental
approval before treatment. Late or lack of treatment for curable STIs increases the likelihood of
adverse consequences. Avoiding treatment also increases the likelihood that partners will not be
treated, and further STI spread.
While young men and women both have increased STI risk, young women are most affected -- adolescent girls
have six times the STD and HIV risk of boys.
ˇ Girls tend to have earlier onset of sexual activity and more biologic factors that enhance their risk for
certain STIs
ˇ Girls tend to have older partners who may have already contracted non-curable (often silent) STIs such
as HIV. In many cultures, the median age of first marriage for women is well under 20 years.
ˇ Young women may have more difficulty negotiating around sex, especially with older, more
experienced partners.
The WHO Global Strategy for STI Prevention and Control (WHO, 2006a) recommends making clinical and
prevention services as responsive and acceptable to adolescents as possible, and lists scaling up of "user-friendly
services" for adolescents among its five recommended new technologies for strengthened response to STI
prevention and control (WHO, 2006a). Important prevention strategies for adolescents in that document
include:
ˇ Promotion of sexual abstinence, delaying sexual debut, and reducing number of sex partners
ˇ Providing education about STIs and how they are transmitted
ˇ Providing condoms (male and female) along with information and demonstrations on their correct use
42
Box 3: How STIs Can Affect Women's Gender Power Balances*
For all women and especially those living in the developing world STIs or their adverse outcomes can
extend beyond health complications alone, and may involve serious, negative social consequences, stigma or
personal harm. For example:
ˇ Youth surveys indicate that one third or more of sexually experienced girls in South Africa are afraid to
"say no to sex," or had been "forced to have sex." Most reported there were times they did not want to
have sex but did so because a "boyfriend insisted." (Kaiser Family Foundation, ;Pettifor et al., 2004)
ˇ A vicious cycle can be set up in which relationships outside marriage lead to STIs and thus to
infertility, and infertility leads to relationships outside marriage and to further spread of STIs
(Dallabetta et al., 2006).
ˇ Syndromic STI management, which does not identify a specific pathogen, can make partner
management difficult and possibly harmful if the male partner is asymptomatic or does not perceive
himself to be infected with an STI. For women with STIs, lack of partner treatment will likely lead to
re-infection. For women with vaginitis that is unrelated to an STI (e.g., caused by bacterial vaginosis),
treatment of a male sex partner who knows he has been faithful may lead to mistrust, conflict, or
physical harm to the woman (Ryan, 1999;Dallabetta et al., 2006).
ˇ STI diagnosis, pregnancy loss, neonatal death, or infertility can lead to conflicts in marital and larger
family relationships, status in the family, partner or other violence, divorce or abandonment. In some
societies, a husband can return an infertile woman to her parents or request return of her bride price
(Dallabetta et al., 2006).
ˇ Infertile women may resort to expensive or risky therapies in a desperate attempt to become pregnant.
Studies in several African nations (e.g., Niger, Uganda and the Central African Republic) have
documented the movement of abandoned or rejected barren women to urban areas where, due to
economic need, they practice prostitution (Frank, 1983).
ˇ In low-income communities, commercial sex (sex in exchange for money) or transactional sex (sex in
exchange for goods) work may be common. Risk behavior surveys indicate that 3 to 30% of women
and 10 to 45% of men in some African settings exchanged sex for money or goods during the past year.
All women who sex for money or goods as a means of survival are susceptible to STIs including HIV;
however, studies suggest that the poorest and least educated women also the least likely to be able to
negotiate safer sex practices as sex without a condom is usually perceived to be worth a higher price
(Dallabetta et al., 2006).
-
The WHO Global Strategy for STI Prevention and Control (2006) includes as a guiding principle that "gender
inequalities must be addressed through interventions that influence political will as well as societal norms and
attitudes concerning sexual behavior and the status of women. Active promotion of male responsibility and the
empowerment of women in the prevention and control of STIs are crucial elements in an effective gender-
sensitive response" (WHO, 2006a).
*Based on studies from Mali, Niger, Uganda, Senegal, Ghana, Central African Republic, Botswana and South Africa.
43
Box 4. Benefits and Limitations to Syndromic Management of STIs
The syndromic approach is based on the identification of "syndrome" -- a constellation of easily elicited
symptoms and recognizable clinical signs associated with a limited number of well-defined STI or RTI
etiologies. The approach is pragmatic in that it can be effectively carried out in almost any setting. The
approach has many benefits (Dallabetta et al., 2006):
ˇ It does not require laboratory facilities (often lacking or unreliable in developing settings).
ˇ Patients are treated at the initial clinical visit. Early treatment minimizes the chance for
complications to develop because of inadequate follow up, shortens duration of disease and thus
reduces opportunities for further transmission to partners.
ˇ Patient costs are less because laboratory tests are avoided, simplified drug regimens are part of the
algorithms, and use of standardized management increases likelihood of effective STI treatment and
need for repeated visits or referrals to other centers
ˇ The major curable STIs are treated without concern of false negative lab results.
ˇ Patient compliance is higher because drugs are available and education is provided in a standardized
manner
ˇ Patient satisfaction is higher, because drugs are more likely to work and services are provided in a
respectful, non-judgmental and confidential manner
ˇ Standardized training on flowcharts and therapeutic regimens allows providers to also be better
trained on critical ancillary prevention strategies (including educational messages, condom
provision, partner notification and referral) as part of routine care
ˇ Standardized regimens allow for improved case-reporting for surveillance, and thus more
information for program management (Ryan, 1999;Dallabetta et al., 2006).
ˇ The approach seems to be particularly successful in treating the STI syndromes most strongly
associated with HIV, genital ulcer and urethral discharge syndromes.
The syndromic approach also has some important limitations (Ryan, 1999;Dallabetta et al., 2006;WHO, 2006a).
ˇ Syndromic management is not useful for asymptomatic patients, who account for at least half of all
STIs. Asymptomatic women with cervical infections are at risk for serious adverse outcomes
including infertility but are not covered by the approach.
ˇ Since genitourinary symptoms are common even in the absence of an STI, the syndromic approach
can lead to false positive diagnoses and thus unnecessary drugs and associated costs, and also raises
the risk of causing drug resistance to certain antibiotics.
ˇ Partner management can be complicated, particularly for women with vaginitis. Many providers are
hesitant to treat sex partners of individuals treated without a specific STI etiology even though
reinfection of the patient would be very likely if an infected steady partner were not treated.
ˇ The most common presenting syndrome, vaginal discharge syndrome in women, is more likely to be
caused by non-STI related reproductive tract infections (e.g., bacterial vaginosis, candidiasis) or
other factors, and vaginitis can be complicated to treat, often requiring multiple visits and repeated
presumptive treatment trials which can be costly.
ˇ Many health care providers, especially physicians, are reluctant to use the syndromic approach
because they were trained in treatment based on etiologic diagnosis.
ˇ In the case of re-focused health workers to specialize in syndromic management of STIs, there is a
risk of "de-skilling" or losing the multidimensional breadth of the health workers due to a limitation
in the services they provide.
44
Box 5. Involving Private Sector Providers in STI Management
In all nations, most STIs are managed by private sector providers, whether formal (e.g., private physicians) or
informal (e.g., traditional healers). Strategies to support the private sector in providing high quality STI care can
greatly improve STI prevention and control in a community.
In Madagascar:
ˇ The government has developed national STI management guidelines that employ locally validated syndromic STI
and RTI management approaches
ˇ National STI program trainers have conducted training courses for private as well as public sector clinicians,
encouraging private physician attendance through a variety of incentives.
ˇ Because of the high prevalence of genital ulcer disease related to bacterial STIs, a pre-packaged STI management
kit for genital ulcer disease including adequate doses of medications against syphilis and chancroid, prevention
messages and male latex condoms, and partner notification cards describing free treatment (both in local
languages) is being marketed to private providers including pharmacists at subsidized cost using a social
marketing strategy.
ˇ High use of the pre-packaged kit by individuals with genital ulcer disease is expected to minimize likelihood that
infected individuals use ineffective drugs, encourage treatment for exposed sex partners, reduce prevalence of
genital ulcer disease in the community and possibly limit HIV transmission (personal communication, USAID,
Madagascar).
In Peru:
ˇ Rates of STIs among symptomatic pharmacy clients were similar to symptomatic patients attending primary care
clinics.
ˇ Pharmacy workers were offered training on STD-HIV management and prevention, especially improved
recognition of syndromes, applying the national syndromic management approach, referral to physicians for
management of STDs and counseling on risk reduction, partner referral, condom promotion and compliance with
and abstinence during treatment (Garcia et al., 1998).
ˇ 56% of pharmacies had staff receiving additional training. After training, counseling for PID and genital ulcers
was more frequent in pharmacies that received specialized training.
ˇ A cost analysis estimated provision of STI care through pharmacies saved 2 USD per case adequately managed
(societal perspective) (Garcia and Holmes, 2003).
45
Annex C. Website links
1. Millennium Development- Goals -- http://www.undp.org/mdg
2. Demographic and Health Surveys http://www.measuredhs.com
3. Centers for Disease Control and Prevention
ˇ Program Operations Tools -- http://www.cdc.gov/std/program
ˇ CDC 2005 STD Treatment Guidelines -- http://www.cdc.gov/std/treatment/
4. World Health Organization (WHO)
ˇ Guidelines for STI management: http://www.who.int/reproductive-
health/publications/rhr_01_10_mngt_STDs
ˇ Fact Sheet, STDs and young people: http://www.who.int/mediacentre/factsheets/fs186
ˇ Fact Sheet, Women and STIs: http://www.who.int/mediacentre/factsheets/fs249
ˇ STI Diagnostics Initiative (SDI): http://www.who.int/std_diagnostics
ˇ Vaccine Preventable Diseases (VPD): http://www.afro.who.int/ddc/vpd
5. Other
ˇ HIV/AIDS Integration Partners Working Group: http://www.fpandhiv.org
ˇ UN, 1994 Conference on Population Development, Cairo: http://www.iisd.ca/Cairo.html
ˇ Alliance for Microbicide Development: http://www.microbicide.org
46
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