In most countries, genital Chlamydia trachomatis (CT) infection is the most frequent bacterial sexually transmitted disease (STD). The infection is often asymptomatic and is sometimes not detected until long after infection. Contact tracing and early treatment are therefore crucial tools when trying to prevent the spread of this disease. Network analysis, tying together sociology and epidemiology, provides a means of looking at the epidemic from a sociogeographic point of view. By highlighting the links between people in sexual networks, it can be useful when designing public health campaigns and carrying out contact tracing.

A workshop on 'Current trends in chlamydia epidemiology in Western societies' was held at Stockholm University on 30 and 31 August, 2007^#. It concentrated on the benefits of analysing sexual networks in the context of CT infections and brought together researchers with medical and social science backgrounds from Europe, Australia, Canada, and the United States.

Contact tracing and network analysis
The power of tracing sexual contacts became clear in a presentation on the situation in the county of Västerbotten, Sweden. Most contacts in that area are traced more than 12 months back, whereas programmes in other places often only trace patients’ history six months back. The population in Västerbotten is younger than in the rest of Sweden and the average number of sexual partners per index case of CT infection is quite high, with 2.5 reported partners per index case, so CT incidence in this area would be expected to be above the Swedish average. However, while following the general rising trend with a similar slope as in the rest of Sweden, the actual incidence of chlamydia infection in Västerbotten is lower than the Swedish average, which may partly be the result from a more efficient contact tracing programme in this area.

Several talks introduced network analysis as a means of obtaining a graphical representation of the links between individuals identified by contact tracing. They focused on the change in contact tracing methods over the years, and on how the knowledge of network structure can influence public health measures. This knowledge can help to identify so-called ‘bridgers’, people who have sexual contact with individuals from separate networks, thereby linking them. By targeting those individuals directly, a large public health effect can be achieved by convincing just one person to change their behaviour and, for example, wear a condom, thereby severing that bridge entirely. The same applies to a sociogeographic context, seeing as the risk of acquiring STDs depends on the social circles one is having sex in rather than on the number of partners. A large-scale contact tracing project carried out in Colorado Springs, Unted States, revealed social locations with a high risk of infection: of 300 bars, only six accounted for 50% of STD transmission; they present an attractive starting point for targeted public health measures. Another insight gained from this project was that while the social circles for HIV infection, hepatitis B and C, and syphilis overlap perfectly, chlamydia patients share only 40% of geographic space with gonorrhoea patients and are between two and three years younger. Knowing the shape of those risk networks can help to determine how to shape an intervention campaign.

How reliable is the information obtained in contact tracing interviews? It was pointed out that there is particular inaccuracy in assumptions people make when asked to place their contacts into social circles such as age, ethnicity etc. While people tend to be clearer about where to draw the boundary between circles they belong to themselves, the information they give on circles they do not belong to is often less reliable.
In contrast, the reliability of reports on the date of contact seems to be sufficient to allow for a deeper analysis of the temporal dimensions of networks. This is an important aspect since the route of CT spreading throughout the network may be limited because certain contacts are only temporary and do not necessarily exist contemporaneously.

Genotyping can be of use in obtaining correct information on sexual contacts and identify clusters not anamnestically found when a rare genotype is involved, but this is not normally the case. The view was put forward that genotyping is interesting from a research point of view, but of limited use in routine diagnosis, seeing as cases in a cluster most often have the same dominant chlamydia isolate.

Reasons behind the current increase in CT
After a continuous decrease during the 1990s in response to the introduction of control programmes, chlamydia incidence reached a minimum around 1997 and since then is rising again. This seems to occur everywhere, in Sweden, Canada, and the US. The probable reasons for the current, continuing increase in chlamydia infections were a recurring point of discussion throughout the workshop. Although there is no clear consensus on this question, the presentations highlighted a few candidates that are more likely than others:

• false positive results due to the new DNA-based test systems
  
• fewer false negative results due to improved methods, more efficient case finding and higher compliance with control rules
  
• chlamydia strains with antibiotic resistance
  
• changes in sexual behaviour
  
• reduced immunity due to shrinking size of networks
  
• 'arrested' immunity
  
• a reservoir in infected men
  

It is considered to be unlikely that the current increase was caused by better tests or better contact tracing, since the same methods have now been in use for quite some time. However, based on a new observation that the average size of chlamydia networks is shrinking (networks with a very large number of members are replaced by networks with fewer members), it was suggested that the immunity in the smaller networks may be lower, and the smaller network size may thus contribute to an increased number of cases.

A possible role of immunity in this phenomenon was supported by a presentation that highlighted the immunology of chlamydia as crucial for interpreting the epidemiology. The natural immune reaction clears the infection within one to three years. CT infection only stimulates protective immunity over time and takes a minimum of 12 months. Treatment therefore leads to ‘arrested immunity’ and increases the risk of re-infection. A further argument in favour of this hypothesis is the fact that the incidence decreases with age. In sex workers, the duration of the sex work reduces the risk of re-infection in addition to the age effect. In parallel, a continuous decrease in pelvic inflammation disease, ectopic pregnancies, and tubal infertility – immunopathologies commonly caused by CT infection – was observed in British Columbia, Canada, since 1993, which may also be a consequence of a population with reduced CT immunity. The slow development of protective immunity could be attributed to either of two mechanisms: multiple rounds of re-infection, or persistent infection. Assuming that the present trend is caused by reduced immunity, only the latter mechanism would be affected in this way by early intervention treatment.

A mathematical simulation was presented that assumed an early intervention in the form of treatment with 80% coverage. It predicted an initial strong decrease of CT prevalence for several years following the intervention, reaching a minimum, and then a rebound which even overshoots the original level and then levelling off at a value slightly below the starting level. The model corresponded closely with the current trend. According to this, we are currently in the rebound phase. In a scenario in which a vaccine rather than treatment is chosen as the intervention, the model predicts a continuous decrease, ending in eradication of CT within a few years.

Another explanation for the recent increase that was discussed was the pool of infected men. The initial decrease in incidence was mostly in women. Case finding was then reduced because the few remaining infected females did not justify the cost, but a pool of asymptomatic infected men that were not treated was left to restart the epidemic. The powerful role that men with asymptomatic urethral chlamydia infection play in community transmission was strongly emphasised in this workshop.

The new variant CT
The new Swedish variant C. trachomatis (swCT) that emerged in Sweden in 2006 – and was first reported in a Eurosurveillance article in November 2006 – was also discussed. It was felt that the variant was initially overlooked because it could not be detected by many of the commonly used test systems. Three different companies had chosen a gene on the C. trachomatis plasmid as the target for their PCR kits in order to take advantage of the higher copy number. The emergence of a variant with a deletion in that gene showed how monopoly generates vulnerability. If only one or two systems had been used in the country, it could have taken a long time to find out. This could have been avoided if an essential chromosomal gene or a dual approach had been chosen for the company kits. The swCT, however, cannot be responsible for the current increase in chlamydia cases, because it only appeared in 2006.

Its spread outside Sweden is surprisingly limited. While every fourth CT case in Malmö, Sweden, is swCT, only a single case of swCT has so far been detected in neighbouring Copenhagen, Denmark, although the two cities are connected by a bridge and share a large number of commuters. This phenomenon might be explained by the fact that the test system by Becton Dickinson which is able to detect swCT, dominates in Denmark. So the swCT was not selected for in Denmark, whereas Sweden, by not treating the undetected cases, selected for swCT.
Men having sex with men (MSM), who tend to have more international contacts and could have spread the infection abroad, did not contribute to the spread of this particular variant because swCT belongs to genotype E which is rare in MSM in Sweden.

Future CT intervention strategies
Although the participants said they were left with more questions after this meeting than before, the general consensus at the end of the workshop was that two types of intervention should be implemented in particular: 1) increased targeting of asymptomatic men in tracing, testing, and treatment, and also in communication campaigns, especially with regards to young men who in general do not tend to seek medical advice very often; 2) extending the time for contact tracing, which would also lead to the inclusion of more male contacts.

Many other ideas were discussed, such as the identification of high-risk social meeting places (e.g. a specific bar or internet site) by including the question of "Where did you meet your partner?" in the interviews. People frequenting those places could be targeted for serology testing.

Although many people were tested and counselled in Sweden, condom use has not increased, suggesting that there may be a need for improved counselling, especially in youth clinics. It was suggested to change the main message from “use pills, and if you want to protect yourself, also use condoms” to “use condoms, and if you want to protect yourself, also use pills”. To date, safer sex campaigns have been centred around HIV and AIDS – those messages may not always be effective for chlamydia.

The Swedish National Board for Health and Welfare is to release a new chlamydia action plan for Sweden that will take on board some of the points discussed in this workshop.

^#The workshop was organised by Fredrik Liljeros and his group at the Department of Sociology at Stockholm University and the Stockholm Group for Epidemic Modelling, with financial support from the Swedish Council for Working Life and Social Research. The speakers were: Johan Giesecke (European Centre for Disease Prevention and Control, Sweden), John J Potterat (consultant for STD/HIV epidemiology and control in the US), Ann Jolly (Centre for Infectious Disease Prevention and Control, Canada), Hans Fredlund (Department of Clinical Microbiology at Örebro University Hospital, Sweden), Björn Herrmann (Department of Medical Sciences at Uppsala University Hospital, Sweden), Monica Nordvik (Department of Sociology at Stockholm University, Sweden), Helena Carre (University Hospital of Umeå, Sweden), Robert C Brunham (University of British Columbia Centre for Disease Control, Canada), Alden Klovdahl (Australian National University), Devon D Brewer (Interdisciplinary Scientific Research, United States), Birgitte Freiesleben de Blasio (University of Oslo, Norway).