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CHAPTER
Introduction to STI
prevention and control
1. Introduction to STI prevention and control
The most widely known STIs are gonorrhoea, chlamydia, syphilis and AIDS — but there are many
more.
The World Health Organization (WHO) estimated that 340 million new cases of curable STIs occurred
in 1999. In other words, almost one million new infections occurred every day.
At the end of 2010, an estimated 34 million people [31.6 million–35.2 million] were living with HIV
worldwide, up 17% from 2001.1
1.1 The transmission of STIs
By far the most common mode of transmission of STIs is through unprotected penetrative sexual
intercourse (vaginal, oral and anal). Contact of intact skin with genital secretions and discharge poses
only a small risk of becoming infected. However, contact of the mucous membrane with infected
secretions poses a greater risk of infection.
Other, modes of transmission include:
❑
mother-to-child transmission:
 during pregnancy (e.g. HIV, syphilis and hepatitis B virus)
 at delivery (e.g. gonorrhoea, chlamydia and HIV)
 after birth (e.g. HIV)
 through breast milk (e.g. HIV)
❑
through the unsafe and unsterile use of needles or injections or other contact with blood or blood-products (e.g. syphilis, HIV and hepatitis).
It is important to remember that the human immunodeficiency virus (HIV) is transmitted in
the same ways as any other STI.
What factors increase the risk of transmission?
Not all acts of unprotected sexual intercourse result in the transmission of an STI from an infected
person to a partner. Whether or not a person is infected depends on many factors: biological,
behavioural and social.
Biological factors
Certain biological factors influence the transmission of STIs. They are age, sex, immune status of the
host and the virulence of the organism.
Age
The vaginal and cervical mucosa in young women is immature and this makes them more vulnerable
to infection than older women. This is due to cervical ectopy, a normal condition for young women,
http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/JC2216_WorldAIDSday_
report_2011_en.pdf
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Introduction to STI prevention and control
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when cervical surface cells more readily allow infections to occur.
Young women are especially at risk in cultures/societies where they marry or become sexually active
during early adolescence. On average, women become infected at a younger age than men.
Sex
Infections enter the body most easily through a mucosal surface such as the lining of the vagina.
Since the mucosal surface area that comes into contact with the infective agent is much greater in
women than in men, women can be more easily infected than men.
Immune status
The immune status of the host and virulence of the infective agent affect transmission of STIs. As we
will detail later in this chapter, certain STIs increase the risk of transmission of HIV — itself a sexually
transmitted infection. HIV, in its turn, facilitates the transmission of some STIs and worsens the
complications of STIs by weakening the immune system.
Behavioural factors
Many behavioural factors affect the chance of getting an STI. Such behaviours are known as ‘risky’.
Personal risky sexual behaviours
❑
Changing sexual partners frequently
❑
Having more than one sexual partner
❑
Having sex with ‘casual’ partners, sex-workers or their clients
Recent or frequent change of sexual partner, having more than one sexual partner or having sex with
sex workers or their clients makes it more likely that a person will come into contact with someone
who has an STI.
❑
Having unprotected penetrative sexual intercourse in a situation where either partner has an
infection
❑
Having had a previous STI in the last year
People who have had an STI in the last year are at risk of getting infected again if they have
not been able to change their sexual behaviour or situation that caused the infection in the first
place.
Other personal behaviours associated with risk
❑
Skin-piercing: this refers to a wide range of practices, including the use of unsterile needles to
give injections or tattoos, scarification or body piercing, and circumcision using shared sharp
instruments
❑
Alcohol or other drugs used before or during sex: alcohol or drugs may diminish the perception
of risk, resulting in not using a condom; or if a condom is used it may not be used correctly.
The behaviour of the partner(s)
A partner with one or more of the following behaviours is more exposed to STIs and, in turn, is more
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likely to transmit an STI:
❑
has sex with other partners
❑
has an STI
❑
injects drugs
❑
has a male partner who has sex with other men.
Social factors
A number of social factors link sex and behavioural issues and may affect a person’s risk for acquiring
STIs.
❑
In many cultures, women tend to have little power over sexual practices and choices, such as
use of condoms.
❑
Women tend to be economically dependent on their male partners and are therefore more likely
to tolerate men’s risky behaviour of multiple sexual partners, thus putting themselves at risk of
infections.
❑
Sexual violence tends to be directed more towards women by men, making it difficult for
women to discuss STIs with their male counterparts.
❑
In some societies, a permissive attitude is taken towards men, allowing them to have more than
one sexual partner.
Which population groups are particularly vulnerable?
In most countries some groups of people are particularly vulnerable to STIs. This may be because
they are exposed to infected partners more frequently or because they are more susceptible to getting
infected each time they are exposed. Such groups include:
❑
sex workers and their clients;
❑
men or women who have multiple sexual partners;
❑
men or women whose jobs separate them from their regular sex partners for long periods of
time, e.g. long-distance drivers, fishermen, uniformed services personnel and migrant workers;
❑
sexually active youth and adolescents.
For various reasons, these people may hesitate to go to health facilities for treatment. Special effort
may be necessary to reach them and make services acceptable to them.
1.2 STIs – the problem
The frequency and distribution of STIs
Epidemiology is the study of the frequency and distribution of a disease in the population.
Key facts
❑
448 million new infections of curable sexually transmitted (syphilis, gonorrhoea, chlamydia and
trichomoniasis) infections occur yearly.
Introduction to STI prevention and control
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❑
Some sexually transmitted infections exist without symptoms.
❑
In pregnant women with untreated early syphilis, 25% of pregnancies result in stillbirth and 14%
in neonatal death.
❑
Sexually transmitted infections are the main preventable cause of infertility, particularly in
women.
❑
WHO recommends a syndromic approach to diagnosis and management of sexually
transmitted infections. (WHO fact sheet http://www.who.int/mediacentre/factsheets/fs110/en/)
Figure 1.1: WHO fact sheet on STIs (No. 110, August 2011)
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The distribution of STIs
In general, the prevalence of STIs tends to be higher in urban areas than in rural ones, in unmarried
people and in young adults. STIs, including HIV, occur in both males and females. However, statistics
rarely show an equal distribution between men and women, nor do they show an equal distribution
between different age groups.
Distribution by age
Most children under 14 years old are not affected by STIs, other than by congenital syphilis,
ophthalmia neonatorum (conjunctivitis) and HIV-infection.
New STI cases begin to occur during adolescence and tend to be most frequent in the 15–44 age
groups, decreasing in older adults.
Distribution by sex
It would be reasonable to assume that men and women are equally vulnerable to STIs. However
cases occur:
❑
more frequently among females than males between the ages of 14 and 19;
❑
slightly more frequently among males after the age of 19.
Why are there these differences?
The higher frequency among females aged 14–19 years may be due to several factors:
❑
the start of sexual activity is usually earlier for girls than for boys;
❑
girls tend to have sex with older male partners, who have more sexual experience and are more
likely to carry infections;
❑
due to the characteristics of the genital tract of young girls, they are especially vulnerable to
infection with STIs.
After the age of 19, the slightly higher frequency among males may be due to:
❑
under-reporting by women because:
 health care services in general may be more accessible to men than women. For example,
where men migrate to urban areas for employment, they have access to the urban services
– and therefore are more likely to appear in statistics;
sexually transmissible infections often produce no symptoms or only mild symptoms in
women.
❍
70% of women and 50% of men infected with chlamydia may not have symptoms;
❍
up to 80% of women and 30% of men infected with gonorrhoea may also have no symptoms.2
Studies have shown asymptomatic infections with gonorrhoea and chlamydia in men to be higher than those shown above.
Clearly, more research will describe the extent of asymptomatic infection in men.
2
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This suggests that as few as 20% of the women infected will forward for treatment – so the rest do not appear in statistics.
 cultural and economic constraints might prevent a proportion of women from attending for
treatment.
❑
men becoming infected after practising unsafe sex with a small number of sex workers;
❑
older men possible being be more sexually active than women of the same age;
❑
men being more likely to change partners than women.
In Pacific Island countries, the best available indicators of STI levels in women are surveys of the
number of women attending antenatal, family planning and gynaecological clinics.
How accurate are national report figures?
Estimates for STIs tend to be higher than the figures in national reports, which are usually based on
the numbers attending health facilities for treatment. This tends to underestimate the true extent of
STIs in the general population, as many cases go unreported. There are several reasons for this.
❑
People with asymptomatic STIs do not seek treatment.
❑
Health facilities offering treatment for STIs may be too far away for many people.
❑
People seeking other health care such as antenatal services may not be routinely screened for
STIs.
❑
Many patients perceive a stigma in attending traditional STI referral clinics, where anyone might
be perceived to be at risk of infection by STIs.
❑
Many people choose to go to alternative healthcare providers, both in the formal and informal
sectors, who do not report STI cases to the authorities.
The complications of STIs
STIs are a public health concern not only because of their high prevalence worldwide, but also
because of their potential to cause serious and permanent complications in infected people who are
not treated in a timely and effective way (see Table 1.1). In addition, they are known to facilitate HIV
transmission.
A UNAIDS Technical Update in May 1998 states that:
Both symptomatic and asymptomatic infections can lead to the development of serious
complications. The most serious complications and sequelae (long-term consequences) of
untreated STI tend to be in women and newborn babies. These can include cervical cancer,
pelvic inflammatory disease (salpingitis), chronic pelvic pain, foetal wastage, ectopic pregnancy
and related maternal mortality.
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Chlamydial infections and gonorrhoea are important causes of infertility, particularly in women,
with far-reaching social consequences. Chlamydial infection is an important cause of pneumonia
in infants. Neonatal gonococcal infections of the eyes can lead to blindness.
Congenital syphilis is an important and significant cause of infant morbidity and mortality. In adults,
syphilis can cause serious cardiac, neurological and other consequences, which can ultimately be
fatal.
The Public Health Approach to STD Control,
UNAIDS/WHO Technical Update, May 1998
Table 1.1: Complications that may result from STIs
Cause
Complication
Gonococcal and chlamydial infection
Infertility in men and women
Pelvic inflammatory disease (PID)
Epididymitis
Ectopic pregnancy due to tubal damage
Gonorrhoea
Blindness in infants
Gonococcal, chlamydial and anaerobic bacterial infections
Pelvic and generalised peritonitis
Acquired syphilis
Permanent brain and heart disease
Congenital syphilis
Extensive organ and tissue destruction in children
Human papilloma virus
Genital cancer
Some more facts about the complications of STIs
CT
FA
Pelvic inflammatory disease (PID), caused by gonorrhoea and chlamydia, is inflammation of the
uterine lining (endometritis), fallopian tubes (salpingitis) and ovaries (oophoritis). The pain from PID is
often the first symptom a woman notices. If the fallopian tubes are damaged when the woman first feels
pain, this damage is irreversible.
CT
FA
PID permanently scars and narrows the fallopian tubes, so increasing the risk of ectopic pregnancy by
seven to ten times. This condition can be fatal for women because the tubes rupture, causing extensive
haemorrhage. Ectopic pregnancies cause an estimated 1% to 5% of all maternal deaths.
CT
FA
PID and infertility – Without treatment, 55% to 85% of women with PID may become infertile. Many
women may lose their fertility without ever realising they had PID.
CT
FA
Gonorrhoea in men can lead to serious complications and sequelae. An infection can spread from the
urethra (where it is known as urethritis) to the epididymis (where it is known as epididimytis). This in turn
may cause infertility.
CT
FA
Ophthalmia neonatorum – Afflicts 5% of the newborn in some developing countries. Without
treatment, it damages the vision of 1% to 6% of affected infants.
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CT
FA
CT
FA
Chlamydia may spread to the lungs of the newborn and lead to chlamydial pneumonia
Syphilis infection during pregnancy – Can spread through the placenta and infect the foetus. Up to
40% of syphilitic pregnancies end in spontaneous abortion, stillbirth or perinatal death. This is particularly
serious when the maternal infection is untreated during the first 20 weeks of pregnancy.
CT
FA
All these complications can be avoided if the correct treatment is provided early, before the
medical conditions develop.
The effect on society
The social and economic burden of STIs can be enormous. Untreated STIs can lead to loss of
employment and broken marriage. For example, one of the biological effects of PID is infertility —
childlessness sometimes leads to divorce and disruption.
STIs can place a heavy financial burden on families, communities and health services. If an epidemic
of STI is uncontrolled, the loss to the national income can be significant.
The extent of these complications arising from untreated bacterial STIs is extensive and severe —
yet all can be avoided if the correct treatment is provided sufficiently early. More importantly, primary
prevention would prevent STI transmission.
The HIV/AIDS epidemic
HIV-infection, which causes AIDS, is spread by the same behaviour as other STIs. In contrast to
most viruses, HIV is slow-acting, taking years to produce illness. The immune defences of an HIVinfected person gradually become weakened over ten years or so. Various bacteria, viruses, fungi and
parasites — known as ‘opportunistic’ pathogens — take advantage of this weakened state to cause
various illnesses.
The needs of people living with HIV are many. They include therapies to treat opportunistic infections,
as well as the anti-retroviral drugs that attack HIV itself. They also need social and psychological
support and counselling to deal with the fear of stigmatisation and the implications of this lifethreatening illness. The provision of effective drug therapies for HIV and opportunistic infections varies
a good deal between countries.
Figures 1.2 and 1.3 give a great deal of information about the HIV/AIDS epidemic.
Comprehensive Sexually Transmitted Infections Management Guidelines
CT
FA
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Figure 1.2: UNAIDS Fact sheet on the Global AIDS Epidemic 2011
Figure 1.3: UNAIDS Fact sheet on the Regional HIV Epidemic 2011
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The link between STIs and HIV/AIDS
The interrelationship between STIs and HIV is complex.
❑
Some STIs facilitate the transmission of HIV.
❑
The presence of HIV can make people more susceptible to the acquisition of STIs.
❑
The presence of HIV increases both the severity of some STIs and their resistance to treatment.
Which STIs seem to facilitate the transmission of HIV?
A person with open sores in the genital area is greatly at risk of contracting and transmitting HIV.
Chancroid and syphilis are the main bacterial causes of sores; if promptly diagnosed and treated, the
risk can be reduced.
Genital herpes also facilitates HIV transmission:
Several studies have shown that people with genital herpes are two to three times more at risk
of contracting HIV. In high prevalence populations of HSV-2, contraction of HIV per sexual act
is approximately five times more likely (Wald et al, 2002; Strick et al, 2006; Celum et al, 2004;
Serwadda et al, 2003 & Freeman et al, 2006) Result from study in 2006 by Reynolds et al also
shows the interaction between HIV acquisition and suppressing HSV-2 shedding.(Reynolds et al,
2006).
Chlamydia, gonorrhoea and trichomoniasis can also facilitate the transmission of HIV. This may be for
any of the following reasons.
❑
These non-ulcerative diseases stimulate the immune system to increase the number of white
blood cells, which are both targets and sources of HIV.
❑
Genital inflammation associated with these STIs can cause microscopic cuts in genital tissues,
creating potential sites where HIV can enter the body.
❑
Inflammation of the genital mucosa leads to an accumulation of white blood cells that are
receptive to HIV.
HIV makes infection with other STIs more likely
People infected with HIV are more vulnerable to getting multiple STIs. This is because changes in their
immune system make them more vulnerable to infection in general.
HIV and increased severity of STIs and resistance to treatment
‘An additional relationship between HIV and other STI…is the alteration of the natural history of
an STI in an individual with coexistent immuno-deficiency associated with HIV. The severity of the
manifestations may be increased, infectiveness prolonged and increased, and the response to
conventional regimens reduced.’
Sexually transmitted diseases: policies and principles for prevention and care,
UNAIDS/WHO 1999.
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We can summarise the links between HIV and other STIs in this way (Figure 1.4).
Figure 1.4: The interrelationship of STIs and HIV-infection
Altered natural history
and susceptibility
STIs
Impaired immunity
HIV/STI interrelationships
HIV
Unprotected sexual
intercourse
The extra and obvious link between STIs and HIV is behavioural: unprotected sexual behaviour
exposes people to both HIV and other STIs.
Equally, the consistent use of condoms can PREVENT both kinds of infection.
1.3 The challenge of controlling STIs
The objectives of STI prevention and treatment are to reduce the prevalence of STIs by interrupting
their transmission, reducing the duration of infection and preventing the development of complications
in those infected.
Why is it so difficult to control the spread of STI?
There are many factors to consider:
❑
factors relating to the health system;
❑
biological factors;
❑
social and behavioural factors.
Challenges arising in the health system
❑
Health services able to diagnose and treat STI may be:
 unavailable or too far away;
 too expensive;
Introduction to STI prevention and control
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 considered to stigmatise and discriminate against those who visit.
❑
There may not be enough emphasis on education and other efforts to prevent infection.
❑
Health services may be unable to offer the most effective drugs, often due to their cost. Growing
resistance to drugs for some diseases requires the use of increasingly expensive drugs to
control them.
❑
A very important barrier and probably the biggest barrier to accessing STI care is the
judgemental attitudes of health care providers. They should be seen by care seekers as
non-judgemental and non-moralistic, and the patient should be assured of privacy and
confidentiality.
❑
Health services are not promoting and providing condoms in sufficient quantities.
Biological factors
We said earlier that as many as 70%–80% of infected women may be asymptomatic and so will not
seek treatment. This also applies to a significant proportion of men. All these asymptomatic people will
continue to be infected, risking complications and perhaps infecting others.
Social and behavioural factors
The social and behavioural factors to consider are many:
❑
reluctance to seek health care. This may be for many reasons, including ignorance,
embarrassment and guilt;
❑
ignorance or misinformation. These powerful obstacles can exist in all age groups and all types
of people. They tend to be widespread among adolescents and young people — the very ones
likely to be most sexually active and at risk;
❑
sexual practices that are deeply rooted in the everyday life of people and their communities;
❑
preference for alternative health sources such as traditional healers;
❑
reluctance to follow safe sex practices for a variety of reasons, including:
 lack of knowledge of safe sex;
 dislike of condoms;
❑
social stigma often attached to STI. This may mean that people hide what they feel is shameful
and so avoid seeking treatment;
❑
failure to take the full, prescribed course of treatment for the STI, for a number of reasons:
 it can take many days to complete;
 the patient’s symptoms disappear and he/she believes that the infection is cured and that
he/she can ‘save’ the medication for another time or other people;
❑
the difficulty of notifying sexual partners, through fear, embarrassment or being unaware of the
importance of doing so;
Comprehensive Sexually Transmitted Infections Management Guidelines
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❑
stigmatisation and discrimination of persons with an STI.
Prevention of STIs
All STIs, including HIV, are preventable. Prevention can be primary or secondary:
Primary prevention aims to prevent people from becoming infected with an STI.
This is about adopting safer sexual behaviour and engaging only in safer sexual acts.
Safer sexual behaviour implies:
❑
abstention from sexual activity altogether;
❑
delaying the age of sexual debut;
❑
lifelong mutual monogamy.
Safer sexual activity implies:
❑
engaging only in non-penetrative sex acts: mutual masturbation and rubbing of body parts;
❑
engaging in penetrative sex acts only if condoms (male or female) are used. Penetrative sex acts
include vaginal, oral and anal sex.
Secondary prevention is about the provision of treatment and care for infected people in order to
avoid further transmission of infection to others.
This may be achieved by:
❑
promoting STI care-seeking behaviour, through:
 public education campaigns;
 providing non-stigmatising and non-discriminatory health facilities;
 providing quality STI care;
 ensuring a continuous supply of highly effective drugs;
 ensuring a continuous supply of condoms.
❑
rapid and effective treatment of people with STI, to include:
 comprehensive case management of STI syndromes;
 training of health care providers in case management.
❑
case finding activities to include:
 examining asymptomatic and minimally symptomatic women attending clinics for maternal
and child health and family planning;
 partner notification and treatment;
 education, investigation and treatment of targeted population groups who may have placed
themselves at risk of infection, such as sex workers, long distance truck drivers, uniformed
Introduction to STI prevention and control
29
service personnel and young people, both in and out of school.
❑
screening for STIs:
 screen persons who are not seeking health care for STIs, based on population groups and
perceived risk groups, including young persons, sex workers, pregnant women, itinerants.
Integration of STI services within primary care
In order to improve access, people with STI should not need to attend a centre devoted to STI
treatment. STI treatment should be available at all health facilities throughout the country.
It is possible to integrate STI care within primary health care — primary care clinics, maternal, child
health and family planning clinics — through the syndromic management and laboratory testing for
STI.
This means that health care providers will need to be trained to recognise STIs syndromically and then
offer their patients comprehensive care.
Managing sexually transmitted and reproductive tract infections (STI/RTI) within reproductive health
settings (e.g. antenatal, family planning, etc.) will require appropriate adaptation. Tools such as the
Essential Care Practice Guides for RTI, family planning, etc. should be consulted for this purpose.
The features of comprehensive care are summarised in Figure 1.5.
Figure 1.5: Features of comprehensive care
Pro
vi
for de a
sy nti
nd b
ro
te Co
st n
in
g
s
tic
io e
m
IV
t
lH
ia onsen
t
n c
e
h
fid wit
Make a diagnosis
of STI
Arrange
for follow
up
Provide
education
fo
ge tm
n
a
ra
Ar tre
r
e
n
t
par
r
en
t
As
se
ss
o f pe r
ris cep
tion
k
Promote and provide
condoms
Syndromic case management of STI blends all these features to deliver comprehensive and integrated
STI care. With the increasing availability of laboratory tests and services in some countries in the
region, the provision of care based on laboratory diagnosis is possible and this will greatly assist in
providing high quality care.
Comprehensive Sexually Transmitted Infections Management Guidelines
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Important
Integration of STI services does not mean dispensing with specialised STI clinics. Specialised
STI clinics should be reserved as reference centres for difficult cases where specially trained
health care providers can give more time to those referred. The other purpose of specialised
centres is the training of health care providers and laboratory investigations to monitor
resistance patterns and distribution of disease, etc. Of course, in some cases, a specialist
centre can be a primary care centre for some patients, if it is the nearest health facility.
Introduction to STI prevention and control
31
Glossary
AIDS
Acquired immunodeficiency syndrome caused by the human
immunodeficiency virus (HIV)
Amniotic sac
Membrane that encloses amniotic fluid and the fetus in the womb
Antenatal
Period between conception and giving birth
Antibiotic
A substance produced by a micro-organism that inhibits or kills
another
Antimicrobial
An agent that kills micro-organisms or suppresses their growth or
multiplication
Cervix
Lower part of the uterus that protrudes into the vagina, often
called the neck of the uterus/womb
Complication
A secondary disease or condition that can arise if the primary
disease is not treated
Congenital syphilis
Syphilis passed from the mother to the child during pregnancy
Conjunctivitis
Inflammation of the mucous membrane of the eyes and eyelids
Ectopic pregnancy
A potentially fatal condition caused by a pregnancy that occurs
outside the uterus (usually in the fallopian tubes)
Epidemic
An outbreak of disease that affects a large proportion of a
population at the same time
Epidemiology
The study of the incidence, distribution and causes of an infection
or disease in a population
Epididymis
An elongated cord-like duct, along the posterior border of the
testis, which provides for storage, transit and maturation of
spermatozoa
Fallopian tubes
The tubes that carry ova from the ovaries to the uterus
Flow-chart
A chart showing the steps that need to be taken to perform a task
Natural history of an infection
The course of an infection if untreated (The natural history of
STIs varies. For example, chancroid eventually heals on its own,
whereas untreated syphilis may spread to other organs and lead
to complications, even after many years)
Ophthalmia neonatorum
Conjunctivitis occurring in a baby less than one month old, usually
due to gonorrhoea or chlamydia infection
Periodic presumptive treatment
Treatment repeated at designated intervals based on judgement
rather than absolute certainty
Sign(s)
An indication of the existence of disease or any objective
evidence of a disease as is perceptible to the examining healthcare provider
Susceptibility to infection
How much resistance the body has to infection (for example, little
resistance would mean that the patient was highly susceptible)
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Symptom(s)
Any subjective evidence or perception of disease or of a patient’s
condition
Syndrome
A set of symptoms and signs giving rise to a consistently
recognisable disease entity, e.g. the syndrome of urethral
discharge
Syndromic case management
Management of a patient whereby a syndrome (a consistent
group of symptoms and easily recognised signs) is used as a
basis for the treatment of the causative organisms.
Urethra
Duct through which urine is discharged from the bladder
Vertical transmission
Infection that passes down from the mother to the fetus (or child)
during pregnancy, delivery or breast-feeding
References
•
Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type
2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185: 45-52 doi: 10.1086/338231
pmid: 11756980.
•
Strick LB, Wald A, Celum C. Management of herpes simplex virus type 2 infection in HIV
type 1-infected persons. Clin Infect Dis 2006; 43: 347-56 doi: 10.1086/505496 pmid:
16804851.
•
Celum C, Levine R, Weaver M, Wald A. Genital herpes and human immunodeficiency virus:
double trouble. Bull World Health Organ 2004; 82: 447-53 pmid: 15356938.
•
Serwadda D, Gray RH, Sewankambo NK, Wabwire-Mangen F, Chen MZ, Quinn TC, et al.,
et al. Human immunodeficiency virus acquisition associated with genital ulcer disease and
herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect
Dis 2003; 188: 1492-7 doi: 10.1086/379333 pmid: 14624374.
•
Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex
virus 2 infection increases HIV acquisition in men and women: systematic review
and meta-analysis of longitudinal studies. AIDS 2006; 20: 73-83 doi: 10.1097/01.
aids.0000198081.09337.a7 pmid: 16327322.
•
Reynolds SJ, Quinn TC. Developments in STD/HIV interactions: the intertwining epidemics
of HIV and HSV-2. Infect Dis Clin North Am 2005; 19: 415-25 doi: 10.1016/j.idc.2005.04.005
pmid: 15963880.
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