Bad medicine: chlamydiaBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2547 (Published 12 May 2010) Cite this as: BMJ 2010;340:c2547
All rapid responses
In a recent onExamination Quiz in the BMJ the answer to a question on
chlamydia screening was "Evidence to support Chlamydia screening is
limited". And the sole concern about an infection that was expressed was
"A positive Chlamydia result causes psychological distress" (1). Perhaps
this is an appropriate response to being told one has an STD.
This quiz followed an article in the BMJ where Dr. Spence denounced
screening for chlamydia as "bad medicine". He suggested that the chlamydia
story is one of "hysterical" communication and poor "evidence" (2).
We think this dismissive attitude towards screening is premature, and
would like to respond to Dr. Spence's assertions. There is, in fact, a
large body of evidence showing that Chlamydia trachomatis, the most
commonly reported sexually transmitted bacterial pathogen, is an important
cause of pelvic inflammatory disease (PID) and the long-term consequences
of PID - tubal factor infertility (TFI) and ectopic pregnancy (EP). To
remind readers of the key evidence accumulated over the last 25-30 years
to support chlamydia screening programs, we summarize below:
a. A 1977 report that 30% of PID cases have C. trachomatis recovered
from fallopian tube aspirates (3) piqued interest;
b. Clinic-based studies found that some chlamydia-infected women
develop PID if treatment is delayed. (4-6);
c. Westrom's laparoscopy studies of women with suspected PID and
follow-up of 1844 women with abnormal findings and 644 with normal
examinations indicated that PID cases had a 5-6 fold increase in failure
to conceive (16% vs 2.7%) and EP (9.8% vs 1.8%) (7);
d. Many women with EP or TFI were found to have high levels of anti-
chlamydial antibody in cross-sectional and case-control studies, but most
had no prior history of PID (8). In one study, 71% of women with EP had
high levels of anti-chlamydial antibody, but only 15% had a PID history
e. The concept of "silent salpingitis" develops with the hypothesis
that inapparent chlamydial infection can cause TFI and EP. This idea was
supported by findings that women with symptomatic PID who were treated
with antibiotic regimens ineffective against chlamydial infection could be
left with clinically inapparent upper genital tract chlamydial infection
(10); additionally >25% of asymptomatic women with seemingly
uncomplicated cervical chlamydial infection were found to have upper
genital tract disease (11);
f. A largely asymptomatic and treatable infection with consistently
high prevalence (12, 13) and serious consequences is a strong candidate
for preventive efforts such as screening;
g. To demonstrate the impact of screening, Scholes and colleagues
selected women at high risk for chlamydial infection and randomly assigned
them to be invited to come to a clinic to be screened for chlamydial
infection or to receive usual care. After one year, the screening group
had a significant 56% reduction in PID incidence (14);
h. A similar (albeit not significant) reduction in PID was seen by
Ostergaard and colleagues in an experimental screening program based on
home sampling (15);
i. Screening programs increased with the introduction of effective
single dose treatment with azithromycin (16), and highly sensitive and
specific nucleic acid amplification tests (NAATs) for diagnosis of
chlamydial infection which can be used on non-invasive samples such as
first-catch urine and self-obtained vaginal swabs (17, 18).
This story unfolded over roughly three decades, during which there
have been secular changes in the prevalence of chlamydia and of its
contribution to PID. For example, when we conducted screening using
culture in San Francisco in the late 1970s and 1980s, we found a roughly
10% prevalence of chlamydial infection in young women attending family
planning clinics (13). The prevalence rates in those clinics are much
lower today, presumably because of screening programs. On the other hand,
a paradoxical increase in incidence and prevalence has been seen in many
screened populations (19, 20).
Few clinicians would disagree that we are seeing less PID, and EP,
although changes in medical management can introduce ascertainment bias
into efforts to reliably estimate the incidence of these outcomes. Most
women with these conditions are now managed on an outpatient rather than
on an inpatient basis (21). The chlamydial contribution to PID is also
lower than it was. The same is true for gonococcal infection. Many of
the women with PID that we see now have non-chlamydial/non-gonococcal PID
and the bacteria associated with bacterial vaginosis are more prominent
(22). Population based estimates of the serious consequences of
chlamydial infection find lower rates than predicted from the clinic based
studies (23). Moreover, follow-up studies of untreated infected women have
found less PID development than was previously observed (24). Together
these suggest that high-risk subsets of women exist that have not been
rigorously identified, and clearly there is still much to be learned.
However, there are recent studies that continue to find chlamydiae to
be important causes of serious genital tract disease. For example, 30%
of the women with PID in Skane county in Sweden have chlamydial infection,
as they did 30 years ago (25). And in some population groups, chlamydial
infection doubled the risk of ectopic pregnancy (26).
The entire situation is very complicated. It is easy to sit back and
criticize. However, the introduction of chlamydia screening was not "bad
medicine" but reflected the best available evidence. Some have felt that
the declines in PID and EP seen as chlamydia screening programs were
introduced were due to these programs, while others feel the two are
unrelated (27). It is obvious that we need more information on the natural
history of chlamydial infection, and innovative trials of contemporary
intervention strategies (27). But such studies are difficult.
The Prevention of Pelvic Infection (POPI) randomized clinical trial
was a valiant recent effort to assess the effect of chlamydia screening in
preventing PID, but ultimately was inconclusive (28). There was
considerably less PID in the initially tested group than in those whose
screening specimens were tested a year later, but the difference was not
statistically significant because the study was not adequately powered as
both the incidence of PID, and the prevalence of chlamydial infection,
were lower than initially assumed. Of the 67 chlamydia-infected women in
the control group, 29 (43%) were tested for chlamydia outside the study,
and thus may have been removed from risk, moving the study result towards
the null. Recent chlamydial infection seemed to be associated with
subsequent PID. Some women who had negative screening tests developed
chlamydia-positive PID within the year. An important question from the
POPI study is whether more frequent screening may be needed to effectively
prevent PID. In addition, it too suggests we need studies to identify high
risk subsets of women for more selective screening.
PID is a well-known diagnostic challenge, but other goals of the
screening programs for chlamydial infection are to prevent TFI and EP (as
well, of course, to prevent perinatal infections when pregnant women are
screened). At the moment, we seem to have relatively few ways of
assessing those outcomes, in part, because of a lack of appropriate
registries, in part because of secular changes, and in part because of
problems in designing appropriate studies. Methods to adequately measure
these sequelae are urgently needed.
Nonetheless, we still have to be aware that this organism is capable
of causing these conditions. Although Dr. Spence's point that chlamydial
infections clear over time is obvious, it is not a very reassuring one
because some infections will lead to serious complications. We have no
way of providing assurance that an individual patient will clear her
infection within a specific time period; or before complications or
transmission occurs. The best evidence from cohort studies suggests that
about half of infected women clear in one year (24, 29) and we have seen
infected women who refused treatment remain culture-positive for up to six
years (JS, unpublished).
Doing nothing and just accepting the consequences is simply
unacceptable. The bottom line is that we need more well defined studies to
assess the impact of chlamydia screening programs to see what their
effects are and how they should be carried forward.
One wonders what Dr. Spence does when he has a sexually active
teenage girl as a patient. Does he not screen for chlamydia if she is
asymptomatic? Does he tell her not to worry about chlamydia? Does he
tell her that even if she does have a chlamydial infection, it will go
away by itself - sooner or later? Does he tell her that she probably
won't develop PID? Does he tell her that she will probably still be
That would be BAD MEDICINE! Really BAD MEDICINE!
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Competing interests: Each of the authors has been involved in industry-supported studies evaluating diagnostic tests for Chlamydia trachomatis.