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interventions against sexually transmitted infections
(STI) to prevent HIV infection
Philippe Mayaud
and Duncan McCormick
+ Author Affiliations
London School of Hygiene and Tropical Medicine, London,
UK
Next Section
Abstract
STIs have taken on a more important
role with the advent of the HIV/AIDS epidemic, and there is good evidence that
their control can reduce HIV transmission. The challenge is not just to develop
new interventions, but to identify barriers to the effective implementation of
existing tools, and to devise ways to overcome these barriers. This
'scaling-up' of effective strategies will require an international and a
multisectoral approach. It will require the formation of new partnerships
between the private and public sectors and between governments and the
communities they represent.
Towards the end of the 15th century,
a devastating epidemic of infectious syphilis swept Western Europe. Observers
at that time quickly perceived the disease to be transmitted sexually, but this
group of 'venereal diseases' was subsequently regarded as unproblematic until
it was noted to be a severe problem among military personnel in the 19th and
20th centuries1. Interest
in sexually transmitted infections (STIs) was further fuelled in the early
1980s by the advent of the HIV/AIDS epidemic and recognition of the role of STI
in facilitating the sexual transmission of HIV2. Interest
in STI control has reached a peak recently when it was shown that many
interventions to control STIs can help reduce the spread of HIV. Furthermore,
this can be achieved through the use of low technology in sustainable and
cost-effective control programmes3.
However, despite decades of control
efforts, STIs still thrive today. There are problems in the effective
implementation of control programmes because STIs are not just biological and
medical problems, but also behavioural, social, political and economic problems
– many facets that have not been adequately addressed in the past. This
realisation is slowly translating into more comprehensive approaches to STI
control involving several disciplines. Yet, there is growing evidence that the
epidemiology of STIs and HIV is changing, and control efforts may be severely
challenged once again.
Previous SectionNext Section
Public
health importance of sexually transmitted infections
Sexually transmitted infections
(STIs) constitute an important public health problem for the following reasons:
(i) STIs are frequent with high prevalence and incidence; (ii) STIs can result
in serious complications and sequelae; (iii) STIs have social and economic consequences;
and (iv) a number of STIs have been identified as facilitating the spread of
HIV.
Previous SectionNext
Section
Epidemiology
of STIs
STIs are caused by over 30
pathogens, including bacteria, viruses, protozoal agents, fungal agents and
ecto-parasites. The World Health Organization (WHO) estimates that
approximately 340 million incident cases of the four main curable STIs
(gonorrhoea, Chlamydia spp, syphilis and Trichomonas vaginalis)
occur every year, with 85% in non-industrialised countries4.
There are, however, substantial
geographical variations in estimated prevalence and incidence. Sub-Saharan
Africa, whilst accounting for 20% of the global STI estimates, has the highest
prevalence and incidence rates. The overall yearly incidence rate of curable
STIs in Africa is estimated at 254 per 1000 people in reproductive ages (15–49
years), but is only 77–91 per 1000 in industrialised countries4. The
second highest rates are found in South and South-East Asia. This is not
surprising given the large at-risk populations of young people in these
countries, and – in the case of China – the recent opening of its borders to
free trade, quickly followed by increases in prostitution and STI, which were
once believed to have been controlled5.
Similarly, in the early 1990s, major political and economic transitions took
place in the Newly Independent States (NIS) of the former Soviet Union. Since
that time, there have been unprecedented epidemics of syphilis and gonorrhoea
with annual increases of 100–300%6. The
reasons for the increase of STIs in many non-industrialised countries are
multifactorial but relate to a great extent to the lack of access to effective
and affordable STI services in many settings7, or to
the collapse of once relatively performant health systems in countries
undergoing harsh economic and health reforms6.
STIs impose an enormous burden of
morbidity and mortality, both directly through their impact on reproductive and
child health, and indirectly through their role in facilitating the sexual
transmission of HIV infection. The greatest impact can be seen among women in
whom severe complications include pelvic inflammatory disease, chronic pain,
and adverse pregnancy outcomes (ectopic pregnancies, endometritis, spontaneous
abortions, stillbirths and low birth weight). In both men and women, STIs play
a major role in infertility. A growing number of malignancies are also
attributed to STIs, notably cervical, anal and penile cancers as well as
hepatocellular carcinoma. Congenital infections in the new-born include
congenital syphilis, ophthalmia neonatorum and pneumonia.
The World Bank has estimated that
STIs, excluding HIV, are the second commonest cause of healthy life years lost
by women in the 15–44 year age group, responsible for some 17% of the total
burden of disease in women of reproductive ages, outranked only by causes of
maternal morbidity8. Yet it
is only in recent years that STIs have been accorded any priority by national
ministries of health or by the international community, mainly because of their
potential interaction with HIV.
HIV–STI
interactions
HIV and other STIs may interact with
each other in the following ways (Fig. 1):
HIV, by causing immunosuppression, can modify the
natural history (duration), clinical presentation (severity), and response
to treatment of certain STIs, notably other viral infections such as
genital herpes simplex virus infection or human papillomavirus STIs, by causing ulceration or inflammation of the
genital tract, may enhance the transmission of HIV by increasing
infectiousness of HIV-positive individuals and/or the susceptibility of
HIV-negative persons
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Fig. 1
Relationships between HIV and other
STIs.
Since the late 1980s, it had been
noted that HIV-positive patients frequently gave a history of past STI or had
serological evidence of past STI (e.g. increased prevalence of
treponemal, chlamydial or herpes antibodies). These studies suggested the
existence of an 'epidemiological synergy' between HIV and other STIs2. However,
one of the major hurdles in understanding this relationship was that HIV and
other STIs share a common sexual transmissibility, driven by common sexual
behaviours; thus, the observed association could be the result of a
'confounding' effect. This could only be overcome at the analytical stage
through statistical methods for 'controlling' for the effect of behaviour, or
in study design, by conducting prospective randomised-controlled intervention
trials.
In a recent comprehensive review,
Fleming and Wasserheit group the evidence that STIs facilitate the transmission
of HIV into three categories9: (i)
biological plausibility studies; (ii) HIV seroconversion studies; and (iii)
randomised intervention studies.
Biological
plausibility or mechanism studies
During sexual intercourse genital
ulcers may bleed, leading to the increased risk of HIV transmission via the
blood route. Studies of HIV infected people with genital ulcer disease (GUD)
suggest that these ulcers may increase infectiousness as HIV virions have
been detected in genital ulcer exudates among patients with chancroid or
syphilis10,11. Similarly,
HIV proviral DNA was found in herpes-associated GUD among men in Seattle12.
Treatment or healing of GUD among HIV-seropositive individuals is accompanied
by a decrease in HIV shedding12,13. Among
HIV-seronegative individuals, GUD may increase susceptibility by
disrupting mucosal integrity, by the recruitment and activation of HIV target
cells, such as lymphocytes, and possibly by HIV taking advantage of CCR5 and
chemokine receptors14.
The effects of STI on excretion of
HIV-1 in genital secretions have been investigated. There is evidence that
among HSV-2 infected women, even in the absence of an ulcer, HSV-2 genital
shedding is increased in HIV-seropositive individuals15,16 and that
both HIV-RNA and HSV-2 DNA shedding are increased in the presence of the other
virus16. The
biological basis for the 'promotion' of HIV infection is not entirely
elucidated but it has been suggested that, in the presence of HSV, HIV can
infect keratinocytes that lack CD4 receptors17.
Non-ulcerative STIs such as
gonococcal or chlamydial infections have also been shown to increase the
frequency of HIV-DNA shedding in cervico-vaginal secretions among
HIV-seropositive female sex workers in Ivory Coast13, and
Kenya18. A study
among male patients in Malawi19 observed
an 8-fold increase in secretion of HIV-1 RNA in semen compared with a control
group. The effect was marked for men having either gonorrhoea or T.
vaginalis infections. In both men and women, successful treatment of
patients with STI resulted in decreased frequency or quantity of HIV shedding13,19.
Changes in the vaginal flora, such
as seen in bacterial vaginosis, appear to be increasing the risk of HIV
acquisition20–22.
However, properly randomised intervention studies are still required to
determine the real causal role of this frequent condition.
HIV
seroconversion studies
Several studies have demonstrated
that prior presence of an STI will enhance HIV acquisition. In Kenya,
HIV-seronegative men attending a STI clinic with a chancroid ulcer were 4 times
more likely than their counterparts without an ulcer to seroconvert in the few
weeks of follow-up23. Other
independent factors of HIV seroconversion included the lack of circumcision and
a sexual contact with a sex worker. In a cohort study of Thai military
conscripts, a significant 4-fold increase in the relative risk of HIV
seroconversion was found among the men who were HSV seropositive at baseline,
and a 2-fold significant increase among men who seroconverted for HSV in the
intervening follow-up24.
Randomised
intervention studies
A large community-randomised
controlled trial conducted in the Mwanza region of Tanzania showed that
improved management of STIs in rural health centres and dispensaries, reduced
the incidence of HIV infection by approximately 40% over a 2-year period25 mediated
by a decrease in the duration of symptomatic STIs26. This
study has provided the clearest evidence to date of the impact of a feasible
and cost-effective STI intervention in preventing HIV transmission.
It has now been realised that the
prevention and care of STIs are interventions which improve the health status
of the population and are also important strategies for the prevention of HIV
transmission. Consequently, UNAIDS and WHO have recommended that high priority
be given to the development of STI control programmes4.
Previous SectionNext Section
Approaches
to STI control
Theoretical
control models
STI control strategies have long
been influenced by the 'transmission dynamics model' described by Anderson27. In this
model, the transmission of a STI is expressed in terms of its basic
reproductive number (R0), i.e. the average number of new (or
secondary) STI cases generated by an index (or primary) case in a defined
population over a period of time. It has been demonstrated that R0
is a function of the rate of partner change (c), the probability of
transmission of the STI during sexual intercourse (β) and the duration of the
infection (D)27 –
summarized in the formula R0 = β × c × D. STI control programmes
should, therefore, aim to reduce the basic reproductive rate by a combination
of strategies, including behaviour change aiming at decreasing the number of
sexual partners, increased condom use and treatment of patients with STI. The
latter component of STI control programmes aims to reduce the duration of
infectivity of individuals with an STD.
This model has also highlighted the
importance of groups of individuals who have much higher rates of sexual
partnerships. These 'core groups' and their sexual partners – who may form
'bridge populations' between the core groups and the general populations (Fig. 277) – have
been shown to be epidemiologically important in driving the STI and HIV epidemics
in many parts of the world28.
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Fig. 2
The structure of sexual networks (reproduced
with permission from: Cates W & Dallabetta G, 199977).
Other models have been developed to
conceptualise the strategies needed to control STI. The 'operational model'
identifies the many different steps that patients with an STI pass through
before they can they can be considered cured by health services (Fig. 3). At each
step, a proportion of patients will drop out. By multiplying the percentages of
patients taking each step, one obtains an estimate of the cure rate achieved by
the health services of interest. This model shows how, in most
non-industrialised countries, only a fraction of STI cases are successfully
treated29. In this
way, it clarifies the four main reasons for failure to control STIs: (i)
failure to prevent unsafe sexual behaviour; (ii) failure of people with
symptoms to access health services; (iii) failure to identify and treat
patients with symptoms; and (iv) failure of health services to provide adequate
treatment.
View larger version:
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Fig. 3
Operational model of the role of
health services in STI case management (reproduced with permission: Laga
M. 12th International AIDS Conference, Geneva 1998)
Each of these steps, in turn,
suggests points for potential medical, health promotion, and service delivery
interventions. Starting from the bottom of the model, broad options for STI
control, therefore, include: (i) improving STI case management, including
partner notification; (ii) improving treatment-seeking behaviour; (iii) case
finding or screening for neglected or asymptomatic STIs; (iv) mass treatment of
the general population and/or presumptive treatment of high-risk groups; and
(v) primary prevention (information education and communication [IEC]
strategies, condoms, microbicides, vaccines).
This paper will review the main
strategies used under each of these approaches as a means to control STI, and
prevent HIV.
Previous
SectionNext
Section
STI
interventions
STI
case management
Early diagnosis and effective
treatment of STIs is an essential component of STI control programmes. The
traditional method for STI diagnosis has been through laboratory diagnosis of
the aetiological agent. Whilst this is still the method of choice in many parts
of the industrialised world, this approach is expensive both in terms of
diagnostics, infrastructure, and maintenance. Additionally, it often results in
delays in diagnosis and treatment. Moreover, most health centres and
dispensaries in non-industrialised countries do not have access to reliable
laboratory facilities. Consequently, clinicians either need to refer their
patients to specialist centres, resulting in further delays, or they attempt to
make a presumptive clinical diagnosis through the identification of particular
clinical features related to various agents. This method has often proven
inaccurate or incomplete30.
To address the limitations of both
aetiological and clinical diagnosis in the management of STIs, particularly for
patients who attend the first level of primary health care, the WHO has
developed and advocated the syndromic management approach. STI-associated
syndromes are easily identifiable groups of symptoms and clinical findings on
which the healthcare providers can base their presumptive diagnosis. Management
is simplified by the use of clinical flowcharts, and allows time in the
consultation to provide simple education messages, discuss partner notification
and promote condoms. Antimicrobial therapy is provided at once to cover the
majority of pathogens presumed responsible for that syndrome, in that specific
geographical area7.
Syndromic management is simple and
lends itself to use in a variety of outlets such as STI clinics, primary
healthcare (PHC) facilities, pharmacies, family planning/maternal and child
health (FP/MCH) services and private practitioners clinics. The sensitivity and
specificity of the approach for the diagnosis and management of urethral
discharge syndrome and genital ulcer syndrome in various settings have been
very satisfactory. Other advantages include cost-effectiveness, diagnosis and
treatment at first visit and increased patient satisfaction7.
There are two main limitations to
syndromic management. Firstly, the cost of over-diagnosis and treatment of
patients with no or only one infection. This includes the direct costs of the
antimicrobials as well as the indirect costs in terms of adverse drug
reactions, alteration in normal gut flora (e.g. shigella) and potential
domestic violence. Over treatment is particularly a problem in areas of low STI
prevalence. A study conducted in Matlab, Bangladesh, found that cervical
infections were present in only 3 out of 320 women complaining of abnormal
vaginal discharge while the prevalence of endogenous infection was 30%31. In this
setting, the WHO algorithm had a sensitivity of 100% but a very low specificity
(56%) while a locally-adapted speculum-based algorithm had sensitivity ranging
between 0–59% depending on the pathogens to be identified with a specificity of
80% up to 97%. Clearly syndromic management in this setting did not deal
adequately with the management of vaginal discharge and it was calculated that
between 36% and 87% of costs would have been spent on uninfected women.
The second limitation is the poor
sensitivity and specificity of the syndromic approach for the detection of
cervical infections in women, even in settings with higher STI prevalence. The
WHO has recommended a risk assessment score to be added to the vaginal
discharge syndrome in order to increase the effectiveness of algorithms7.
Evaluation of this approach has taken place in several countries, but has
yielded disappointing results7: scores
need to be setting-specific, with tremendous variations even within the same
country; the performance of algorithms was not vastly improved; and, as in the
case of the Matlab study, risk score was also found to be inadequate in
societies where most women will not admit to extramarital or premarital sexual
activity for threat of social sanctions31.
Partner
notification
Partner notification (PN) is a
strategy consisting of contacting sexual partners of STI patients to offer them
screening and treatment. PN aims to reduce asymptomatic disease in the
community and shorten the average period of infectiousness. This, in turn, is
expected to reduce disease transmission in the population32. However,
while bacterial STIs can be identified and cured, thus breaking the chain of
transmission, viral STIs such as HSV-2 and HIV have no cure and the rationale
for PN is less obvious. In the context of syndromic management, it is even less
clear which STI should be treated. The most practical approach has been to give
the same treatment as for the index case, but this will clearly result in
over-prescription of antibiotics. Very little work has been done to demonstrate
the impact of PN on reducing the prevalence and incidence of STI in the
population.
There has been more research to
determine the best way to implement PN. There is strong evidence that simple PN
forms given to the index patient ('patient referral') can be effective, and
less labour intensive and costly than 'provider referral', where the services
take responsibility of tracing contacts. Overall, it seems that PN is
relatively ineffective in situations where there is low motivation of health providers,
where sex with anonymous partners (e.g. sex workers) is common, where
there is a high rate of sexual partner change and where resources are scarce
and addresses unreliable33.
Acceptability of PN depends upon confidentiality and availability of treatment32, but
strategies should take into account the sexual practices and ethnicity of the
population as well as potential negative impacts such as violence against the
index case (especially women).
Promotion
of treatment seeking behaviour and the role of the private sector
A key step where many STI patients
can be lost in the operational model is 'attendance to services'. Surveys of
health-seeking behaviour in non-industrialised countries indicate that a
substantial proportion of people with symptomatic STI seek treatment in the
informal or private sector, from traditional healers, unqualified practitioners,
street drug vendors, and from pharmacists and private practitioners and will
only attend formal public health services after alternative treatments have
failed34. Self-medication
is also very popular in many settings, where up to 65% of men with symptoms of
urethritis self treat34–36.
Patients seek care in the private
sector for many reasons. Public services often have restricted and inconvenient
opening hours35 while
private services tend to tailor their opening times to suit their clients.
Moreover, provider-to-client ratios vary greatly between sectors in many
countries. For example in Lagos State, Nigeria, Green found a ratio of one
traditional healer per 200 population, whereas in Mozambique, the physician to
population ratio was 1:50,00037. In
addition, private sector services are often seen as providing a more
personalised and confidential service with less social and cultural distance
between client and provider34,35,37. An
additional barrier to public services utilisation is sometimes the cost of
services, as was evidenced in Nairobi, Kenya: when user fees were introduced, a
huge decrease in monthly attendances of the largest STI clinic in the city were
recorded. Lifting of the fees a few months later resulted in increased
attendances, although this never reached the same levels38.
Quality of care in the private
sector is difficult to assess due to the range of services offered and the
difficulty in accessing practitioners. A study of private doctors in South
Africa showed that fewer than one in ten patients received adequate doses of
antibiotics and in 75% of cases an incorrect drug was prescribed39. In
private practice there is a financial incentive which can affect the quality of
care. In some cases, private practitioners may provide a sub-optimal dose of
antibiotics in order that the client can afford treatment and in other cases,
for example in China, practitioners may increase their income through over
investigation and over prescription (Mabey D, personal communication).
There has been a number of
interventions to improve private sector management of STIs. In Jamaica,
seminars were provided for public and private physicians and nurses and
post-training tests showed an increase in knowledge with regard to STI
diagnosis, and most practitioners reported an increase in risk reduction
counselling40.
Similarly, training for pharmacists in Nepal showed an increase of 45% in the
correct syndromic treatment of urethritis41. This
figure dropped to 26% nine months after the training, indicating the need for
continued training and supervision42. A study
in Thailand using 'mystery shoppers' again showed improved treatment of STIs by
drugstore staff after training43.
Another strategy to increase
effective treatment of STIs is the use of pre-packaged therapy (PPT) for
syndromic treatment. A team in Uganda developed the 'Clear Seven' kit for
patients with urethral discharge, which contains ciprofloxacin, doxycycline,
condoms, partner referral cards and a clear instruction leaflet. The kit was
socially marketed in clinics, pharmacies and retail drug shops. The study found
that 'Clear Seven' users versus controls had significantly higher cure
rates (84% versus 47%, P > 0.001), greater compliance (93% versus
87%) and increased condom use during treatment. Partner referral rates were
similar for both groups44. Similar
PPT kits have been used in Cameroon and South Africa with varying levels of
acceptability by both health service staff and patients45,46.
In general, the private sector
should be viewed as a complement to, and not a replacement for, effective and
accessible public services. Furthermore, the views of government health
authorities and the medical community should be considered when attempting to
stimulate effective collaboration between the sectors.
Screening
and case finding
Case finding is the testing for STI
in individuals seeking health care for reasons other than STI, and screening is
defined as testing for STI in individuals not directly seeking health care (e.g.
blood donors). Both strategies have an important role in the detection and
treatment of asymptomatic STIs in the community. They should be principally
directed towards ANC, FP and MCH clinic attendees as well as high-risk groups
such as adolescents and sex workers.
Universal serological testing of ANC
attendees for syphilis is recommended by WHO and is one of the most
cost-effective health interventions available although programmes are poorly
implemented in many countries47. Donors
of blood, tissue and semen should be screened for at least syphilis, HIV and
hepatitis B in order to protect recipients, and the potential exists for
screening of populations such as military recruits and company employees. In
all cases, careful attention should be paid to patient confidentiality, and if
necessary counselling and treatment.
There is an urgent need for simple
and cheap methods of identifying asymptomatic women with cervical infections in
antenatal, family planning and maternal child health clinics. A simple
sociodemographic risk score which identifies women at greater risk of infection
has been tried but it has a poor sensitivity and predictive value48,49.
Mass
treatment
Mass treatment involves the single
or periodic administration of effective drugs to a whole population in order to
treat, reduce the reservoir, and prevent continued transmission of a specific
infection. Mass treatment of STI has many potential advantages: asymptomatic
patients are covered, no screening tests are needed, it can be combined with
syndromic treatment services and may be highly cost-effective. However, there
are concerns about the ethics of treating healthy subjects, adverse effects of
treatment, development of drug resistance, logistical difficulties and expense.
It has also been suggested that mass treatment may create a false sense of
security and result in risk compensation behaviour.
Between 1994 and 1998, a community
randomised trial was conducted in Rakai, Uganda, to test the hypothesis that
repeated rounds of mass treatment for STI would reduce STI rates and HIV
transmission50. The
intervention comprised single dose oral treatment of all individuals with very
effective antibiotics (azithromycin and ciprofloxacin) in the study areas and a
single intramuscular penicillin injection for all patients with serological
syphilis. Results showed significant reductions in the prevalence of some STIs,
particularly among pregnant women in the intervention group. However, in
contrast to the Mwanza study mentioned above, there was no effect on HIV
incidence.
Reasons postulated for this
paradoxical result include differences in the stage of the epidemic (mature
epidemic in Rakai versus an earlier stage in Mwanza), differences in
accessibility to STI services for patients with re-infection (continuous
availability in Mwanza, intermittent in Rakai) and differences in the
prevalences of treatable STI (higher proportion of GUD due to HSV-2 in Rakai
than in Mwanza). It was concluded that the proportion of HIV infections
attributable to the enhancing effect of STIs seems to decrease with the
progression of the HIV epidemic51. The
results of a third community randomised trial conducted in Masaka – adjacent
district to Rakai, with the same epidemiological setting sharing the same
epidemiological features but based on a similar intervention to the one used in
Mwanza – are awaited with great anticipation.
It may be that single or multiple
rounds of mass treatment combined with continuous availability of syndromic
management could be an effective control strategy for many countries52. In the
face of looming epidemics in Asia and elsewhere, this option needs to be fully
explored. However, the comparative advantages of mass treatment and continuous
provision of syndromic treatment should be determined through RCTs with STI
services as standard provision in the control group51.
Targeted
periodic presumptive treatment
Targeted interventions are based on
the concept of core groups, which play a key role in the epidemiology of HIV-128. The
'epidemiological synergy' between STI and HIV is particularly important in core
groups with a high incidence of STI and HIV. Moreover, Plummer showed in Kenya
that progression to HIV disease is more rapid in prostitutes and it is likely
that this rapid progression is related to concurrent STI infection28. This
could have an important effect on accelerating the epidemic as frequent
episodes of STI would accelerate the development of lowered immunity and
increased HIV infectiousness while also increasing susceptibility to STIs.
Core groups are context specific
and, when designing interventions, it is important to take account of the
social and economic forces creating these groups and to balance disease control
measures against the potential for victimisation. Interventions need to be
designed in partnership with core group members they should be context specific
and emphasise common goals and interests53.
An example of a successful core
group intervention took place in a South African mining community. The Lesedi
project54 provided
STI treatment services including periodic presumptive treatment and prevention
education to a core group of sex workers living around the mine. The study
found that the intervention significantly reduced the prevalence of gonococcal
and chlamydia infections (NG/CT: Neisseria gonorrhoeae/Chlamydia trachomatis)
and GUD among women. Moreover symptomatic STIs were also reduced among the
miners in the intervention area as compared to miners living further away54. The
results of this study suggest that periodic presumptive treatment coupled with
health education is a feasible approach to providing STI services to core
groups.
Primary
prevention
Primary prevention can be directed
at changing the behaviour of individuals and these are particularly effective
at reaching areas of need, especially when implemented in a clinical setting.
These interventions often rely on the 'rational health model', which is based
on the assumption that an individual has the power to make necessary changes.
However, in many instances drugs/poverty/gender can diminish an individual's
ability to act on his/her intentions55.
Behavioural interventions are particularly important in adolescents as they
have high rates of STI and are more susceptible to behaviour change
intervention such as mutual monogamy, safer sexual practices and condom use.
Many behavioural interventions for primary prevention of STI are similar to
those for the prevention of HIV transmission. As these are discussed elsewhere
in this volume, this paper will focus on those interventions specific to STIs.
Condoms
When used properly and consistently,
condoms are one of the most effective methods of protection for individuals
against STI. They are relatively cheap and free from side effects. They can be
made readily available on a large scale through free distribution or social
marketing – the promotion and use of marketing techniques to make products
available at an affordable price.
However, in many countries only a
small proportion of the sexually active population use condoms and those who do
may do so irregularly and only with selected partners56. Barriers
to consistent use of condoms include high price in some settings, low
availability and inadequate social marketing but above all, lack of appeal to
potential users. Women may also be forced into unprotected intercourse as a
result of unequal power relations between men and women.
In Thailand, the 100% Condom
Programme overcame many of these barriers and the programme has been linked to
the decrease in the numbers of cases of STI and HIV57. However,
similar declines in disease prevalence have been observed in Uganda where
condom uptake is low58. It has
been suggested that a large increase in condom use could fail to affect disease
transmission at a population level due to a 'risk-compensation' mechanism58. This
would imply that condom users switch from inherently safer strategies of
partner selection and low rates of partner change, to a riskier strategy of
maintaining higher rates of partner change plus reliance on intermittent condom
use.
UNAIDS recommended best practice for
condom programmes include campaigns to improve information, education and
empowerment of individuals so that they can make informed decisions about
condom use; ensuring easy access to high quality condoms; and conducting
context specific research into behaviour and preferences as regards condom use56.
Female
controlled methods of STI prevention
STIs disproportionately affect
women, and adolescent women are at increased risk of STI due to ignorance of
appropriate preventative measures ,and unplanned or coercive sexual
intercourse, where it may be difficult or impractical to negotiate safer sex.
Female-controlled methods of protection against HIV and STIs are, therefore,
taking on increased importance.
The female condom has important
advantages such as efficacy, little reported disruption of sexual enjoyment,
safety and in some areas increasing acceptance by women59. However,
disadvantages include high cost, lack of visual and auditory appeal, difficulty
of use, pre-planning of intercourse and mixed reactions among male partners. A
randomised study conducted among sex workers in Thailand has demonstrated that
women who were trained on using female condoms in addition to male condoms
became more consistent users of either method and had, therefore, higher rates
of protected intercourse, compared to women to whom only male condoms were
promoted and provided59.
Vaginal microbicides potentially
offer a female-controlled means of protection from both infection and conception
and have been under development since the early 1990s. Currently, there are
about 36 compounds under development60. These
compounds can have advantages over the female condom in that they can be
developed with options for surreptitious use.
A detergent based chemical
nonoxynol-9 (N-9) kills STI and HIV in vitro but while clinical trials
suggest that the product provides some protection against gonococcus and
chlamydia, results are disappointing for HIV61. There is
also concern that repeated use of these compounds can disrupt the vaginal and
rectal epithelium and actually make users more susceptible to pathogens60. This is
a problem especially for female sex workers who would want to use it a lot.
New compounds are under development
and evaluation. Studies using BufferGel (ReProtect) have shown positive
spermicidal effects and also a decrease in symptoms of bacterial vaginosis60 a
condition which is highly prevalent in some areas and which increases
susceptibility to HIV infection20–22. Other
studies have shown that an antibody-based microbicide that persists in the
vaginal tract for 2–3 days may be feasible. This would be useful for women who
have multiple sexual contacts in a setting where it is difficult to re-apply a
microbicide regularly. It is possible that anti-retroviral agents already
approved for systemic treatment may be used intravaginally and in fact many
researchers predict that 'intravaginal chemoprophylaxis' may require a
combination of agents to be optimally effective.
Vaccines
Vaccines have enormous potential in
the prevention and control of STIs and some are currently under development for
Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex
virus, human papilloma virus and HIV. However, there are difficulties in making
effective vaccines available for use by those in need.
Firstly, many STI agents do not
evoke lasting immunity even subsequent to natural infection. Agents such as N.
gonorrhoeae and HIV are constantly evolving and this makes it difficult to
create a reliable and widely applicable vaccine. Secondly, there are problems
with the logistics of vaccine delivery. A vaccine against hepatitis B has been
available for about 20 years but most sexually active adults remain unprotected
today. The practicalities of vaccination are well known through experiences
with the EPI immunization programmes, but another important issue for STI
vaccines is acceptability by the target population. Unique barriers to STI
vaccine acceptance are likely to be encountered. For example, it could be
argued that STI vaccination in adolescents would condone extramarital sex and,
despite evidence to the contrary, such arguments are still used in opposition
to sex education or condom distribution programmes at schools. Zimet suggests
that issues around consent (parental and adolescent) are likely to be key and
that substantial research will be required in order to guide programme design62. Thirdly,
vaccination may influence sexual behaviour by promoting a feeling of
invulnerability with a subsequent increase in risky behaviour.
Individual,
community and targeted intervention strategies
An important consideration in STI
control is to decide on strategies that target the individual, the community or
special groups of individuals at higher risk of, or more vulnerable to, STIs
within communities. Clearly, a number of strategies target the individual such
as screening, case management and partner notification, whilst community
strategies will include mostly primary prevention such as information,
education and communication (IEC) campaigns, or vaccine programmes. In recent
years, strategies to control STI through mass treatment programmes have been
attempted.
Interventions targeted at
individuals may fail to identify or influence behaviours of people at some
level of risk but who do not identify themselves with the target group. On the
other hand, although general population or community measures deliver a less
intensive dose of intervention to each individual, it is distributed across a
large population that includes many individuals at low risk. It has been
suggested53,55,63 that both
types of intervention are appropriate at different points in the epidemic. At
the start of an epidemic when individuals at risk are difficult to distinguish,
general population interventions are appropriate. Targeting is indicated when
sexual mixing patterns have been identified and later, when the epidemic moves
into the general population and core groups have emerged, universal
interventions are needed.
STI control programmes need a mix of
individual and general population interventions. The challenge is how best to
use and combine interventions and how to make sure policy and political support
is conducive to help change the social or physical environment in which risk
takes place. For example, restrictive policies about prostitution will hamper
interventions targeting sex workers; sociocultural environments which promote
homophobia or deny sexual health information to adolescents will prevent access
of these vulnerable populations to appropriate sexual health services, or may
encourage clandestine risk-taking. Economic empowerment of women can also be
effective.
Previous SectionNext
Section
Challenges
in STI control
Integration
of STI prevention and care in reproductive health services
There is general consensus on the
need to integrate STI services into reproductive health services. The rationale
is that reproductive health programmes are already high profile and could
attract additional funds necessary for STI treatment. In addition, integrated
services could reach a wide female population.
It has been suggested that, at a
minimum, STI/HIV risk assessment and prevention services should be provided in
all MCH/FP clinics, and that integrated services should also include syphilis
testing and treatment for all pregnant women attending antenatal services47.
In economic terms it is thought that
integration will optimise resources, reduce service delivery costs and patient
transport costs as well as other opportunity costs relating to multiple health
service visits64. However,
there is little evidence that integration is in fact an effective public health
measure65. A study
of health systems in sub-Saharan Africa suggests that pre-existing vertical
management and separate service delivery have hindered efforts to translate
concepts into practice. For example, in Kenya the provision of drugs essential
for STI treatment has remained separate from existing systems of procurement
and in Ghana FP management has remained separate from other 'integrated'
services. South Africa, on the other hand, has been more successful in
developing an integrated and comprehensive service. This has been facilitated
by South Africa's strong commitment, since 1994, to universal access to
comprehensive primary healthcare (PHC). The South African approach has
integrated all financial, human resources and logistical systems at provincial
level, and the national programmes provide technical support to services
through horizontal management systems at all levels. But the South African
system is not trouble free. The provision of free comprehensive care has lead
to increased demands on the health system and this has stretched the capacity
of staff at health facilities as well as finances available for effective
drugs. In addition, as elsewhere, an emphasis on clinical care has tended to be
at the expense of health promotion services65.
It is important to note that
integration of STI services can miss one of the largest target groups – men.
This is an important group as men, due to sexual behaviour and increased
mobility, are at higher risk, initially, of contracting STI. However, once
infected, the clinical management of men is simpler than for women.
Investigators in Bangladesh found that there was a substantial unmet need for
STI services for men and that, in addition, there was a demand for other
reproductive and psychosexual services. It may, therefore, be appropriate to
provide comprehensive reproductive health services to men as well as women and
this may even prove to be an effective strategy for the control of STI66.
The
changing epidemiology of STI
Additional challenges to STI control
include the capacity of pathogens to develop resistance to antimicrobials, and
the emergence of some pathogens (HSV-2) or conditions (bacterial vaginosis) as
novel significant causes of morbidity, including facilitation of HIV
transmission.
Global
antimicrobial resistance of N. gonorrhoeae and Haemophilus ducreyi
At present most regions of the world
have a high prevalence of N. gonorrhoeae and H. ducreyi isolates
resistant to common antibiotics such as penicillin, tetracyclin or
cotrimoxazole67.
Resistance is most common in areas of the world where effective treatment is
unavailable or expensive and where diagnostic facilities are inadequate (Fig. 4). The
high costs of effective agents such as azithromycin and ceftriaxone raise
concerns that low or inadequate doses will be used and that this will
facilitate the selection of resistance to these drugs also. Conversely, the
decreasing costs of agents such as quinolones may precipitate their improper
use and self-medication, also leading to increased resistance.
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Fig. 4
Antimicrobial resistance of N.
gonorrhoeae in selected countries in the 1990s [Adapted from: Ison CA,
Dillon JR, Tapsall JW, 199867].
In order to provide effective
treatment and prevent the transmission of resistant isolates, regimens need to
be tailored to the prevalence of antimicrobial resistance in the locality. This
in turn requires information on patterns of anti-microbial susceptibility. Many
industrialised countries have programmes for N. gonorrhoeae
surveillance, but continuous susceptibility data has been lacking in
non-industrialised countries. This problem has been approached by the
establishment of a global surveillance network – the gonococcal antimicrobial
susceptibility programme (GASP). Co-ordinated by WHO, GASP aims to create a
network of laboratories which will monitor susceptibility of gonococcal
isolates and disseminate information on trends in susceptibility and resistance
(Fig. 4). The
network is only effectively working in the West Pacific and the Pan-American
regions, but efforts are underway to promote the establishment of such networks
in Africa.
Surveillance of H. ducreyi
requires a viable culture of the organism. This is a barrier to effective
surveillance as isolation of H. ducreyi is particularly difficult and
often has a sensitivity of 67. In
addition, few centres have facilities for culture. Our knowledge of H.
ducreyi resistance is limited to irregular sentinel surveillance data and
hence the global prevalence of antibiotic resistant H. ducreyi is
unknown67.
The
emergence of HSV-2 and the changing pattern of genital ulcer aetiologies
World-wide prevalence rates for
infection with HSV-2 have been increasing over the last decades. In the US,
recent seroprevalence studies indicate that 22–33% of the population is
infected with HSV-2, representing a 33% increase over the past 20 years68. High
seroprevalence rates of HSV-2 (40–70%) have been recorded in population-based
studies in East and Southern Africa69.
In countries where syphilis and
chancroid are endemic, HSV-2 has traditionally been thought to be relatively
less important as an aetiological agent of genital ulcer disease (GUD). This
pattern is changing however69. Recent
studies have found that, while GUD attributable to HSV-2 infection is
increasing, H. ducreyi is decreasing in many areas. HSV-2 now typically
represents 40–50% of detectable GUD aetiologies in some settings (Fig. 5). The
implications of this increasing problem only begin to be fully appreciated.
Given the fact that HSV-2 and HIV may have a synergistic effect, increased
levels of HSV-2 in GUD will promote susceptibility to HIV or infectiousness of
HIV-infected individuals, whilst HIV will contribute to the further spread of
HSV-2 as well as the worsening of the natural course of GUD cases which will
lead to many apparent failures of treatment. One consequence is that it may be
important to revise the WHO guidelines for syndromic management of GUD69 and
possibly include anti-HSV treatment. Intervention trials evaluating the
feasibility and impact of such treatment strategy, with an important outcome in
terms of HIV shedding, are urgently required16.
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Fig. 5
Proportion of genital herpes or
HSV-2 isolation over time among patients with genital ulcerative disease in
selected sub-Saharan African settings. [Adapted from: O'Farrell B, 199969]
The
role of vaginal and endogenous infections
Greater more attention has been
accorded in recent years to bacterial vaginosis (BV) as a possible significant
factor in women's sexual ill-health world-wide. BV is one of the most common
causes of vaginal symptoms among women of reproductive ages and is associated
with serious obstetric and gynaecological complication, including premature
rupture of membranes, preterm birth and low birth weight infants, as well as
pelvic inflammatory disease or endometritis following insertion of
intra-uterine devices (IUD) or induced abortion70. Recent
investigations in Thailand20, Uganda21 and
Malawi22 have
reported associations between BV and HIV, suggesting a possible causal factor
in HIV transmission.
Although the role of BV in women's
health in non-industrialised countries has not been fully explored, it is potentially
significant as suggested by high prevalence rates (20–50%) and the frequency of
BV-associated morbidity in these regions. Moreover, even a moderate
relative-risk may translate into a large population-attributable fraction of
HIV infection.
It will be important to understand
better the determinants of acquisition or maintenance of BV in women, including
the role of hormonal factors, menstrual and sexual hygiene. The main obstacles
to the control of BV are the difficulty of diagnosing the condition in primary
health care clinics lacking microscopy and trained laboratory personnel, and
the frequent relapse of the condition despite treatment. The challenges,
therefore, will be to devise simpler and more effective methods to diagnose and
treat BV and ways to implement and evaluate large-scale BV control programmes
in non-industrialised countries71.
Mobilising
policy, priority setting and capacity building
The failure to control STIs in the
past was not solely due to antibiotic resistance nor to any emergent or
resurgent organisms, but simply through lack of political will to invest in
control measures72. In order
to mobilise policy, it is vital to identify the barriers that prevent research
findings being translated into policy at country level3. One such
barrier is a lack of appropriate models of service provision which facilitate
the design of effective STI control programmes. Another is the lack of
operational research into ways of adapting international research findings to
the national context.
Many governments are reluctant to
confront the STI and HIV epidemics and in many instances countries fail to
prioritise activities in the face of severe financial and administrative
constraints73. Spreading
resources across programmes in many sectors risks stretching already scarce
resources with negligible or even negative impact. An alternative approach for
policy makers would be to implement a smaller, core set of interventions on a
national scale and in this way provide a foundation for expansion of activities73.
The operational model of STI control
discussed above makes it clear that curative services alone contribute a small
fraction to STI control efforts and will not solve the problem. It is
essential, therefore, to build national capacity in areas that interact
synergistically with case management to create an effective and sustainable
approach to STI control. Training in all areas is essential and this needs to
take place in a policy environment which enables managers to advocate for
policy changes which can improve and sustain the national capacity to implement
an effective STI control programme.
Previous
SectionNext Section
Future
research orientations
In order to control STI better in
the future, a number of important research questions will need to be answered,
and a number of research strategies will need to be explored:
Operational research is required to establish the
effectiveness of existing interventions and improve the implementation of
these interventions in specific contexts. For example, operational
research to refine and adapt context specific syndromic management
algorithms and to assess the cost-effectiveness of various STI case
management approaches. Randomised controlled trials (RCTs) are required to
examine the comparative efficacy and cost-effectiveness of different
partner notification strategies as well as research into cheap strategies
for improving patient attendance. There is an urgent need for the development and
field-testing of simple rapid diagnostic tests for N. gonorrhoeae
and C. trachomatis so that asymptomatic infections can be detected
and treated. Research is required to rationalise available and future
diagnostic techniques in order to guide choices as to who should be
tested. The development of vaccines and vaginal microbicides is
especially urgent for the incurable viral STIs (HPV, HSV-2, HIV). Both the
World Bank and UNAIDS have stated that their organisations are making a
strong commitment to purchase and distribute effective microbicides when
they become available. There is a need for RCTs to assess the effectiveness of
primary prevention and behavioural interventions, particularly among
vulnerable populations such as adolescents, using STI and HIV incidence as
outcome measures. One such trial is currently underway in Mwanza,
Tanzania, but more are needed in different cultural and epidemiological
settings. Capacity building is an important pre-requisite to
enable research in non-industrialised countries and this needs to be
developed along with functioning support structures, access to information
and positive feed-back – in the form of publications, grants and policy
change74.
In 1999, the World Bank indicated that the
international community has the responsibility for ensuring the production
of global public goods75.
However, funding for research and the development of new technology may be
a problem when private firms do not have sufficient incentives to develop
the technology – the main beneficiaries live in impoverished countries
that cannot afford to pay. It is, therefore, a priority to promote
public-private partnerships to develop medical products, and to conduct
research into how this may best be achieved.
Previous
SectionNext Section
Conclusions
STIs have taken on a more important
role with the advent of the HIV/AIDS epidemic, and there is good evidence that
their control can reduce HIV transmission. Although many cost-effective tools
such as condoms, effective drugs and the syndromic approach to case management
are already in existence (Table 1), there
is an urgent need for research into more interventions such as vaginal
microbicides, vaccines and behaviour change.
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Table 1.
Public health package for STI
control: the key elements
However, even where existing tools
are available, there are barriers to the effective utilisation of these tools (Table 2). These
barriers include unavailability or unsuitability of STI services, cultural
factors in sexual and health-care seeking behaviour, difficulties in the
provision of essential drugs, a lack of political will to develop appropriate
policies, and financial support for STI control programmes.
View this table:
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Table 2.
Challenges for effective STI control
The challenge, therefore, is not
just to develop new interventions, but to identify barriers to the effective
implementation of existing tools, and to devise ways to overcome these
barriers. This 'scaling-up' of effective strategies will require an
international and a multisectoral approach. It will require the formation of
new partnerships between the private and public sectors and between governments
and the communities they represent76.
Previous SectionNext Section
Footnotes
Correspondence to: Dr Philippe Mayaud, Clinical
Research Unit, Department of Infectious and Tropical Diseases, London
School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT,
UK
Previous Section
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