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External recognition of services
provided by STD Services motivates further efforts to continue to extend
our current programs. In September 2001 STD Services won a media award
from the Public Health Association for our recently upgraded web site.
Expansion of stdservices.on.net incorporated new content which focussed on
the public health activities of STD Services, and extended sexual health
information suitable for clients of the clinic and students. The website
allows prompt dissemination of information about changes in current
treatments, based on public health surveillance data. Web publication of
STD Services reports provides timely data on the number of sexually
transmitted infections, trends in disease activity and describes high risk
exposures for notifiable STD in South Australia. The award is a tribute to
the work of Dr Chris Miller, inaugural webmaster at STD Services
Attendance at conferences allows
clinicians to refresh and update aspects of research and development in
STD, and review activities away from the usual distractions of the
workplace. The International Congress of Sexually Transmitted Diseases is
a major biennial conference, whose venue alternates between Europe and
America.
International Congress of the Sexually Transmitted Diseases, Berlin
2001
The 2001 biennial International Congress
of the Sexually Transmitted Diseases was held in Berlin at the Haus am
Kollnishen Park, a former High School for the Communist Party of East
Germany. The organisers were the International Union against the Sexually
Transmitted Infections (IUSTI) and the International Society for STD
Research. Other sponsors included CDC, Atlanta and the American Social
Health Association. In addition to the formal scientific program of
plenary sessions followed by a choice of symposia or proffered paper
sessions, there were daily, lighthearted debates on topical issues. The
theme of many posters was the re-emergence of gonorrhoea in Europe and
USA, where there is evidence for increases in rates in both heterosexual
and homosexual populations.
An early session included an
"Update on nucleic acid amplification tests (NAAT) for detection of
Chlamydia trachomatis and Neisseria gonorrhoeae", described a new
assay system. In the discussion, to the question "Can Chlamydia
trachomatis be eradicated?" was the answer, "only if we have
better tests". This was based on the premise that the sensitivity and
specificity of current chlamydia tests has been over-rated because of
dependence on discrepant analysis. The estimate of the sensitivity and
specificity of NAAT was 85% and 89% respectively. The Aptima assay, when
assessed without discrepant analysis, reported a sensitivity and
specificity of 97% and 99% respectively. In further discussion on the role
of NAAT in the diagnosis of gonorrhoea, Dr Edward Hook III stated the
sensitivity of culture to be 90% in men, with a specificity of 100%. He
also considered NAAT on urine to be equivalent to urethral culture for
men.
Another symposium was "Women’s
Health: New perspectives in chlamydia testing" where Sweden's
chlamydia program was outlined. After a plateau of cases in the late 1990’s,
a 30% increase in positives occurred in 2000-01. A Roche health economist
argued that polymerase chain reaction (PCR) is efficacious and effective
in screening programs and that the more control effective a program is,
the less cost effective it becomes. He argued for a new area of modeling
to investigate the use of screening techniques in low prevalence
populations.
One debate topic was the proposition
that "Gonorrhoea will be an Untreatable Disease in 10 years
time". Catherine Ison, a UK hospital scientist presented the no case.
Her argument was that we have the technology to overcome any resistance to
antibiotics by developing new tests and new antibiotics. Joanne Dillon, a
research scientist presented the yes case. She took a broader view of
untreatable and emphasised that not only are the antibiotics failing, but
also our strategies for control.
In the industrialised world gonorrhoea
may be struggling, but in the developing world it is thriving. Hong Kong
data show 70% of strains have quinolone resistance and China has reported
a ceftriaxone resistant strain. There was a plea to develop more
interventions, along with more basic and applied research. An increase was
noted in strains associated with asymptomatic infections (proline,
citrilline, uracil dependent strains), which will make control efforts
more difficult. While new antibiotic products are being marketed by
pharmaceutical companies, these are modified, old classes of antibiotics.
In a major plenary entitled
"Chlamydia trachomatis – the persistent pathogen", Dr Walter
Stamm was one of the presenters. Key points included:
- There is no differential transmission between male
and female if a NAAT is used
- chlamydial persistence can be demonstrated in cell
culture and animal models of tubal infertility
- PCR cannot differentiate between re-infection and
recurrence; culture and comparison of strains is needed to do this
- persistence may occur in vivo, but seems to be rare.
We may fail to detect antibiotic
resistance as few laboratories culture chlamydia; resistance occurs
infrequently and is partial rather than absolute. Dr Stamm referred to
heterotypic chlamydial strains containing mixed populations of resistant
and sensitive cells, which may be more biologically fit to persist. A
reported increase in asymptomatic infections may also promote persistence.
PCR testing is considered better than culture for detecting infection in
men with low polymorph counts on urethral smear.
In a plenary on Mathematical Modelling,
Dr Roy Anderson pointed out that eventual decline in incidence with time
is the natural dynamic of epidemics regardless of interventions. Models
have a long way to go to predict all the reality, and this means more
research on understanding networks and intervention effects. Dr Anderson
described the use of mathematical models in understanding the dynamics of
CD4 lymphocyte levels over time. Lymphocytes can be viewed as a population
at risk, with an incidence and prevalence of infection over time. Hence,
epidemic equation models may provide some insight to better understand the
basic biology of viral dynamics in vivo. Noting that less than 85%
adherence leads to HIV treatment failure, such models may help answer
questions about the value of drug holidays and more specifically their
impact on the development of mutations.
One symposium focussed on chronic
genital conditions, including recurrent vulvo vaginitis and chronic
prostatitis. Dr J Sorbel made some interesting points:-
- Recurrent vulvo-vaginitis (defined by greater than
four proven episodes of Candida vaginitis), not colonization, occurs
in 5-7% of adult women,
- there is much self-diagnosis and use of
over-the-counter preparations, but one study showed only 39% of women
purchasing these preparations for thrush had Candida
- part of the problem is that all currently available
drugs are fungistatic.
Dr Galuzzi Grax outlined the NIH
classification of prostatitis, which now only contains acute and chronic
bacterial prostatitis plus chronic pelvic pain with or without evidence of
inflammation. Prostatic massage and urine tests have never been properly
validated and should not be performed. The aetiology of chronic pelvic
pain is unknown and low rates of specific infections have been reported.
Discussion covered neuromuscular theory which hypothesises that reflux of
secretions into the prostate cause a chemical prostatitis, if this is
correct then µ blocker treatment should assist. Unfortunately there are
no randomised clinical trials (RCTs) to answer the question. A cytokine
theory for the aetiology of the pain was also discussed, but a mechanism
for the initial production of cytokines remains obscure. The few RCTs on
treatment all have high placebo response rates and current therapies are
ineffective.
Another plenary was an overview of STI
and Cancer by Dr Harald Hausen, where the only STI discussed was the human
papilloma virus (HPV). Cervical cancer is monoclonal and only a small
proportion of HPV-infected women develop cancer, so HPV is necessary but
not sufficient cause. The discussion covered a variety of additional risk
factors e.g. hormones, other infections, smoking, genetics and
immunosuppression. There is good evidence that oestrogen plays a role in
cancer formation and this may explain fewer HPV related cancers in men. Dr
Hausen emphasized the complicated immunology and immunochemistry of the
HPV-human cell interaction.
At a symposium on RCTs, Anne Buve from
Belgium posed the question "How relevant are RCT to behavioural
strategies for STD Control?" In her view an intervention may have an
impact but not one being measured, and careful scrutiny of both trial
design and measurement of effect is required. A second point was that the
results of many trials could not be generalized to other populations. An
excellent presentation by Dr Peterman from CDC entitled "Warning: a
good RCT will answer your question!" followed up on Dr Buve’s point
about measurement of effect. He emphasized the need to play close
attention to the study question. As an example, the Muanza and Raki
studies each had different questions but neither was designed to answer
the question "Does STD control reduce HIV incidence?". Richard
Hayes from the Muanza Team reiterated the message, stressing the need for
careful design to measure the impact of an intervention. He noted that
surrogate end points can be misleading and RCTs with a community focus
require specific statistical techniques for analysis.
During a Mathematic modeling, Sexual
networks and STI Control symposium, Geoff Garnett addressed the issue of
persisting low prevalence of STD in industrialized countries where
heterogeneity and long-lived asymptomatic infections fail to explain
persistence. In low prevalence communities mating tends to be random
rather than assortative and reintroduction of infection does not explain
maintenance of infection, nor does drug resistance or the existence of a
core group. A likely explanation is the structure of sexual networks, with
large networks likely to prevent extinction. Hence the past focus on
sexual networks should enhanced by more emphasis on social network
research. In one contact tracing study, 31% of chlamydia cases were
detected in the social network as opposed to the sexual network.
Similarly, in the past decade geographical and network analysis in the USA
has used area of residence of the network, but the venue may be more
important.
On the final day, HIV related
presentations in the major plenary focused on Public Health aspects of
HAART. Dr Anne Johnson outlined conflicting views: treatment allows an
increased duration of infection which may lead to increased prevalence and
increased resistance to treatments. Alternatively, good therapeutic
strategies will reduce infectiousness but this in turn may promote an
increase in partner change rates, more frequent unprotected sex and an
increase in STI’s. She emphasized that prevention efforts should focus
on those who are infected, as life-long strategies to prevent transmission
to others are needed.
Dr Mike Cohen's main thrust was that
HAART is an underutilized prevention strategy. He cited data showing the
increased proportion of STI in HIV positives was attributed to those with
HIV, who were previously unaware of their HIV status. Dr Ward Cates
promoted the concept of preventing HIV by targeting HIV prevention
counseling to those who were infected. The aim is to promote testing so
that everyone knows their status allowing HIV-positives to enter into
health care sooner rather than later. This raises the issue of whether to
treat earlier to lower transmission, knowing that people will be exposed
to drugs for longer periods potentially increasing serious or life
threatening side effects.
The conference was a timely update on
the latest trends in research and a review of currently accepted dogma and
Berlin was a marvellous city in which to spend mid-summer.
Russell Waddell
November 2001
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