Tracking gonorrhoeaResearchers are exploring the genetic diversity of Neisseria gonorrhoeae to identify linked cases of gonorrhoea and help target interventions. |
The sudden, frightening outbreak of SARS in 2003, and its effective containment, highlighted the importance of tracing contacts in controlling the spread of infectious diseases.
However, when the infection in question is a sexually transmitted one, such as gonorrhoea, asking patients about their contacts can be a bit trickier. "Some patients with gonorrhoea are unwilling to discuss their sexual practices or disclose how many people they have slept with; others simply can't remember," says Professor Catherine Ison, a researcher at Imperial College London.
The consequences of failing to trace sexual contacts can be severe: left untreated, gonorrhoea can cause pelvic inflammatory disease, infertility and ectopic pregnancy, and it can be life-threatening. These health risks, together with a substantial increase in cases of gonorrhoea and the alarming rise in antibiotic-resistant strains, have made gonorrhoea a major public health concern and underlined the importance of contact tracing.
Faced with incomplete information from reticent or forgetful patients, Professor Ison and colleagues are turning to microbiology to do some detective work for them - by exploiting one of N. gonorrhoeae's most effective weapons: its genetic diversity.
The DNA of the infecting organism, Neisseria gonorrhoeae, is constantly changing. While this variability enables it to evade host responses, it also leads to large numbers of distinguishable gonococcal genotypes circulating within a community. "The advantage of that for us is that if we can identify a cluster of identical genotypes, it suggests the people they came from are sexual contacts and belong to the same transmission chain," explains Professor Ison. "This is particularly likely if they live in the same area, or frequent the same bar or club, and the samples are collected within a short time period.
"Once we've established that people are part of the same transmission chain, we'll be able to identify core groups who are contributing to the spread of gonorrhoea and start active interventions. These could involve notifying partners and social networks of people in that core group, and distributing posters and leaflets in known meeting places such as bars and clubs. We want to make people aware that they might have gonorrhoea and get them to get tested and treated if necessary."
For their approach to work, the team needed a precise and reliable method for measuring genetic variation in gonococci. To that end, Professors Ison and Spratt and colleagues at Imperial developed a new technique, based on the sequences inside two highly variable genes, por and tbpB. Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) is a simple, automated procedure that enables large numbers of gonoccocal isolates to be analysed.
The Imperial team will use the new technique to analyse the gonoccocal isolates collected from 13 genitourinary medicine clinics in London over a six-month period. "This is a feasibility study to find out whether we can produce the data quickly enough to inform clinicians and direct interventions," explains Professor Ison. It is the first time that a microbiological approach, rather than one based on patient data, has been used to identify transmission chains for a bacterial STI.
Speed is of the essence here because gonorrhoea has a very short incubation period (three to five days), and is therefore transmitted swiftly in a community. This is where NG-MAST really comes into its own. "NG-MAST is a very fast method for typing DNA. Once the patient sample has been taken, the infecting strain can be isolated and sequence-typed within one or two weeks."
If the study is successful, it will mark a big leap forward for microbiology. "We want to make microbiology more proactive in helping patients with STIs," says Professor Ison. "At the moment, clinics fill out KC60 forms, so cases are reported retrospectively to the Health Protection Agency. But what happened in the last four years doesn't direct patient management - we want to look at what's happening now."
Things are looking promising, but Professor Ison has a couple of caveats: "The technical data is very precise, but it doesn't tell you everything. It can identify a transmission chain, but it can't tell you who had sex with who, and never will." The molecular information provided by NG-MAST will, where possible, be combined with epidemiological information collected directly from the patient. "What is very satisfying is that when patients do name each other, they confirm the transmission chains identified by NG-MAST, which indicates that the sequence-typing has given us accurate data."
Professor Catherine Ison is Director of the Sexually Transmitted Bacteria Reference Laboratory at the Health Protection Agency, Colindale, London, and has a position at Imperial College London. Information is released through the publicly accessible NG-MAST website.
External links
- Neisseria Gonorrhoeae Multi Antigen Sequence Typing website hosted by Imperial College London
- Health Protection Agency
Further reading
Martin I M C, Ison C A, Aanensen D M, Fenton K A, Spratt B G (2004) Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J. Infect. Dis. 15 April
Ward H, Ison C A, Day S E et al. (2000) A prospective social and molecular investigation of gonococcal transmission. Lancet 356: 1812-1817
O'Rourke M, Ison C A, Renton A R, Spratt B G (1995) Opa-typing: a high-resolution tool for studying the epidemiology of gonorrhoea. Mol. Microbiol. 17: 865-875

