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Rapid urine test for Chlamydia trachomatis

Source agency:

ANZHSN

Date of Submission:

01/12/2009

Date of Printing:

05/02/2012

Disclaimer:

This report is work in progress and should not be used for external distribution without permission from the originating agency. Users should be aware that reports are based on information available at the time of research and often on a limited literature search.

Technology, Company & Licensing

Technology name:

Chlamydia Rapid Test

Technology - description:

The Rapid Chlamydia urine test requires subjects to provide a urine sample, collected using the FirstBurst urine collection device which collects the first 4-5 ml of urine. The urine is diluted with distilled water and centrifuged. The supernatant is discarded and the pellet is extracted by the sequential addition of the three kit solutions. A fraction of the extracted sample is added to a tube which contains lyophilised amplification and detection reagents. After mixing, the test strip is added to the solution and incubated at room temperature for 25 minutes. The test strip is embedded with a monoclonal antibody to chlamydial lipoploysaccharide. If chlamydia is present in the sample a line appears on the test strip (Nadala et al 2009).

Company or developer:

The University of Cambridge and Diagnostics for the real World (Europe)

Reason for database entry:

Large, asymptomatic infectious population with numbers of infections increasing rapidly.

Technology - stage in early warning process:

Assessment complete

Technology - stage of development:

Other

Licensing, reimbursement and other approval:

The Evaluators have been unable to ascertain whether or not the Chlamydia rapid test has FDA approval or CE marking. Australian TGA approval is not required for a diagnostic test.

Technology - type(s):

Diagnostics

Technology - use(s):

Diagnostic

Patient Indication & Setting

Patient indications:

Sexually active males and females

Disease description and associated mortality and morbidity:

Worldwide Chlamydia trachomatis infection is a major public health problem and one of the most common sexually transmitted bacterial infections. The majority of testing for Chlamydia is conducted on symptomatic cases or as a result of contact tracing, and as such remains under-diagnosed. However, approximately 40-50 per cent of males and 70-85 per cent of females infected with Chlamydia are symptomatic (Vajdic et al 2005). If left undetected and untreated chlamydia infection may move into the upper genital tract causing inflammation and scarring in the reproductive tracts of both males and females. The most common complications of chlamydia infection in women include pelvic inflammatory disease (PID), urethritis, cervicitis, tubal infertility, chronic pelvic pain and ectopic pregnancy, a cause of maternal death and morbidity in the first trimester. In untreated women, 10-40 per cent of chlamydia infections may result in PID, and of these, 20 per cent will become infertile. Chlamydia infection can be transmitted to the neonate at birth, causing conjunctivitis and pneumonia (Hocking & Fairley 2003; Walleser et al 2006; Watson et al 2002).

Number of Patients:

In Australia and New Zealand, the rate of chlamydia infection has been steadily increasing for a number of years, with chlamydia now the most common notifiable disease. Notification rates are likely to be an underestimate of the true rate of chlamydia infection as the majority of tests are performed on symptomatic patients (40-85% of infected individuals may be asymptomatic) or as a result of contact tracing (Vajdic et al 2005).

In Australia, there were 73.5 per 100,000 population notifications of chlamydia infection in 1999, the first year that all states and territories reported notification data. This number has increased every year and in 2008 the notification rate was 273.8 per 100,000. The Northern Territory recorded the highest number of notifications in all years, however this is likely to be due a high number of chlamydia infections of the eye (Communicable Diseases Australia 2009). True prevalence data are difficult to obtain. An Australian systematic review identified 40 studies that used PCR to identify individuals infected with chlamydia. The mean overall prevalence of genital chlamydia infection was 4.6 per cent, 95 % CI [4.4, 4.8], which the authors considered indicated an over-sampling of high-risk groups in the included studies. Mean community-based rates were similar for non-Indigenous males and females (1.5% and 1.4%, respectively). Mean community-based rates for Indigenous men and women were 7.5 per cent (95% CI [6.4, 8.6]) and 8.7 per cent (95% CI [7.9, 9.7]), respectively. The overall mean estimate for adolescents and young adults was 3.3 per cent, 95 % CI [2.8, 3.9] (Vajdic et al 2005).

A recent Australian study reported on the medical records of women (mean age 27.7 years, range 12.2 -80.7 years) using the Melbourne Sexual Health Clinic from 2003 to 2007. All new clients to the clinic underwent a chlamydia test, regardless of their reason for visiting the clinic or whether they were symptomatic for chlamydia infection or not. Over the 5-year period, 10,498 chlamydia tests (PCR) tests were performed and an overall prevalence of 5.9 per cent (95% CI [5.5, 6.4]) was reported. Women less than 25 years had the highest rate of positive tests at 8.1 per cent. The authors report that the positive chlamydia tests are increasing by 12 per cent per year (O'Rourke et al 2009).

As reported in a previous summary , an Australian prevalence survey of chlamydia among young women (aged 18-35 years) was conducted in Melbourne between March 2003 and June 2004. Of the 11,001 households chosen at random, 979 women were eligible and interviewed and of these, 657 provided a urine sample. A total of six cases of chlamydia were detected (five aged 18-24 years and one aged 25-35 years), with an overall prevalence of 0.9 per cent. The prevalence was 3.7 per cent (95%CI [1.2, 8.4], n=135) in the 18-24 years group and 0.2 per cent (95%CI [0.0, 1.1], n=489) in the 25-35 years group. All women who tested positive were asymptomatic (Hocking et al 2006).

Prevalence data for New Zealand are difficult to obtain. Annual testing for chlamydia within the Waikato District Health Board region rose from approximately 18,000 tests conducted in 1998 to 23,338 tests in 2002, and remained at that level until 2006. In 1999, 7.7 per cent of tests were positive, however this rate rose to 11.3 per cent in 2005 but declined again in 2006 to 9.6 per cent (Morgan 2008). A later study again conducted in the Waikato region, reported that there were 21,104 Chlamydia tests carried out during Feb-Oct 2008. Of these, 10,847 (51.4%) tests were tests on 15-24 year olds, 82.3 per cent of whom were female. Using census data for the region, these figures represent 22.2 per cent of the region’s 15-24 year olds, which was made up overwhelmingly of 37 per cent of the region’s young females compared to 7.7 per cent amongst males. Overall 15.8 per cent of tests from 15-24 year olds were positive, 14.4 per cent in females and 23.0 per cent in males (p<0.001), with positivity double amongst Mäori (24.2% vs. 12.5%; p<0.001) (Morgan & Bell 2009).

New Zealand laboratory surveillance indicates an overall increase in the rate of reported chlamydia infection over time. In the quarter from April to June 2009, 37,678 chlamydia tests were conducted with 2,708 (7.2%) testing positive from 2,562 patients. Sixty-six per cent of all positive tests were aged 15-24 years. The Waikato region reported testing 7,379 samples for chlamydia with 768 being positive (10.4%) from the same number of patients. Seventy-five per cent of all positive tests were aged 15-24 years. Almost the same figures were reported from Bay of Plenty laboratories. The overall rate of chlamydia infection in these regions for the quarter April to June 2009 was 211.4 per 100,000 population (STI Surveillance Team 2009).

Technology - specialities(s):

Mens Health & Sexual Health, Infectious disease, microbiology & GUM, Health promotion and protection incl. screening, Gynaecology, women's sexual health, benign breast disease

Technology - setting(s):

Community and primary care

Setting - further information:

 

Impact

Alternative and/or complementary technology:

Substitution technology

Current Technology:

The gold standard diagnostic test for Chlamydia trachomatis currently in use in Australia and New Zealand is PCR. PCR is highly specific and sensitive, especially in comparison to culture, and will only identify Chlamydia trachomatis and not Chlamydia pneumoniae or Chlamydia psittaci (psittacosis) infection. The PCR test amplifies a fragment of specific DNA from the cryptic plasmid of chlamydia, and is capable of detecting only one chlamydia cell in the sample. The PCR test for Chlamydia trachomatis can be performed on first void urine in males and females, avoiding the need for urethral swabs, however endocervical swabs are also suitable. For swabs, a specific PCR swab specimen collection transport kit must be used (Ferguson 2005). Samples for PCR testing must be sent to a certified pathology laboratory.

Health Impact:

It has been proposed that the Rapid Chlamydia urine test will enable a test and treat regimen, with patients undergoing the test, obtaining the result and if needed receiving treatment all in the one clinic visit.

Diffusion:

The Rapid Chlamydia Test is not currently available in Australia.

Cost, infrastructure and economic consequences:

The Wellcome Trust were contacted via email for pricing information, however no reply was received by the evaluators. In the previous summary in 2006, which described the use of a dipstick assay for trachoma using the same principles, Diagnostics for the Real World aimed to have a two-tiered price range. Developing countries would be able to access the FirstBurst Trachoma test for approximately 70 cents per dipstick test, however prices would be higher in developed countries such as Australia (personal communication University of Cambridge, May 2006).

Ethical, social, legal, political and cultural impact:

 

Evidence & Policy

Clinical evidence and safety:

The Rapid Chlamydia test was first trialled in the UK for women attending a sexual health clinic (site one) or two genitourinary medicine clinics over a six-month period. All women over the age of 16 years attending the clinics were invited to attend. All participating women provided a self-collected vaginal swab and a first-void urine sample (FVU). At sites two and three, women also provided a clinician-collected vaginal swab. The majority of women attending site one were asymptomatic (98.2%) and were attending for contraception or reproductive health services. Many of the women (67%) attending sites two and three, however, reported symptoms including vaginal discharge (46%), lower abdominal pain (23%) or pelvic inflammatory disease (3%). Urine samples were divided, with one half sent for PCR chlamydia testing at an independent laboratory and the other subjected to the Rapid Chlamydia test (level III-2 diagnostic evidence). A total of 1,349 women took part in the study. The mean age of participants varied between the clinics: site 1 (n=663), mean age 18.5 years (range 16-27.4 years); site 2 (n=385) mean age 25.4 years (range 16-49.7 years) and site 3 (n=301) mean age 27.8 years (range 17.1-54.8 years).

There was no significant difference between vaginal swab collection methods when compared to PCR. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for self-collected swabs was 81.5, 98.7, 84.6 and 98.4 per cent, respectively. The sensitivity, specificity, PPV and NPV for clinician-collected swabs for the same women was 77.8, 99.2, 89.4 and 98.1 per cent, respectively. The difference in performance of the Rapid Chlamydia test between self- and clinician-collected vaginal swabs was not significant (p=0.096). When self-collected swabs from all centres were compared to the gold standard PCR, the sensitivity, specificity, PPV and NPV values were 82.7, 98.8, 85.8 and 98.5 per cent, respectively. When only the asymptomatic subjects from all three sites were considered, the Rapid Chlamydia test had an overall sensitivity of 80.5 per cent when compared to PCR. It is unclear from the study why a vaginal swab was the preferred method of testing as opposed to testing of the urine sample. The majority of women (95.9%) were comfortable collecting their own vaginal swab. Self-collected swabs were the preferred method of sample collection for 40.7 per cent of women, with 37.5 per cent preferring a urine sample. The remaining 27.7 per cent of women did not express a preference. Seventy-five per cent of women were prepared to wait between 30 minutes and two hours for test results, with only 6.9 per cent preferring to wait less than 30 minutes (Mahilum-Tapay et al 2007).

In order to reduce or slow the steadily increasing rate of chlamydia infection in the population, it has been suggested that more widespread and systematic testing and treatment of males would reduce the infective pool and prevent transmission to females. Therefore a test which makes it quicker and easier to test males via a urine sample rather than a painful urethral swab may be advantageous. Males over 16 years (n=1,002) were recruited over a 12-month period at two of the sites described in the above study (one sexual health clinic, one genitourinary clinic) (level III-2 diagnostic evidence).

To optimise the urine collection method, participants were randomised to provide two urine samples using two different methods. One group provided a urine sample using the FirstBurst collection device, then after a two hour interval the second sample was collected using a conventional cup. The second group reversed the order of sample taking. The FirstBurst collection device, regardless of whether the sample was taken first or second, provided a sample with a significantly higher bacterial load when compared to the conventional cup device (p<0.0001). To further analyse the optimal collection mode, 31 chlamydia positive males provided a urine sample using the FirstBurst collection device and fractionation system, which allowed four distinct fractions from the one urine void. The importance of collecting the first fraction for chlamydia testing, and thus optimising bacterial load, is emphasised by the results. The first fraction (4.6ml) contained a mean bacterial load of 38,561 plasmids/ml with the number decreasing significantly with the second, third and fourth fractions yielding 5,219, 1,669 and 270 plasmids/ml.

The performance of the Rapid Chlamydia test using both FirstBurst and cup urine specimens were compared to the gold standard PCR in 534 randomly collected samples. PCR detected chlamydia infection in 34 of the FirstBurst urine samples (positivity rate 6.4%) and in 33 of the cup collected samples (6.2%). The Rapid Chlamydia test had a sensitivity of 82 per cent when the FirstBurst sample was used compared to a sensitivity of 47 per cent for the cup collected samples. The overall specificity of the Rapid Chlamydia test was high at 98.8 per cent (Wisniewski et al 2008).

Having established the optimal collection conditions for urine samples from males (collecting the first 4-5ml of a urine sample using the FirstBurst collection device), Nadala et al (2009) enrolled 1,277 young males (>16 years) attending the same two clinics described by Wisniewski et al (2008) (level III-2 diagnostic evidence). The majority of men attending site one were asymptomatic and were attending for contraception or reproductive health services. However, 62 per cent of subjects (467/749) enrolled at site two reported symptoms including urethral discharge (21%) and painful or difficult urination (23%). In addition, three per cent of participants were attending the clinic after being identified via contact tracing. Of those eligible, 1,211 provided a usable urine sample. Samples were tested for the presence of chlamydia using the Rapid Chlamydia test and the reference standard, PCR. Twenty participants were identified as positive for chlamydia infection by PCR at site one (4%) and 90 (12%) at site two. The overall sensitivity and specificity of the Rapid Chlamydia test was 81.8 and 98.5 per cent, respectively (see web link Table 1).

The authors reported a significant difference between the PPV and NPV values obtained at the two sites (p=0.009 and p=0.028, respectively), which may reflect differences in prevalence of chlamydia infection between the two sites. The likelihood ratios of a positive and negative result from the chlamydia test from both sites and sites combined are summarised in Table 2.

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Table 2
Positive and negative likelihood ratios for test results with Rapid Chlamydia test

Site Positive
1 (n=454) 50.0
2 (n=757) 61.5
Total (n=1211) 54.5

Adjusted total (range)
43.1 (15.0-55.1)

Site Negative
1 (n=454) 0.102
2 (n=757) 0.202
Total (n=1211) 0.185
Adjusted total (range)
0.184 (0.177-0.477)
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Of the 20 participants found to be positive for chlamydia at site one, 18 (90%) were asymptomatic at presentation. At site two, 28 (31%) of those found to be positive had no symptoms. Of these asymptomatic men, 16/18 (89%) and 20/28 (71%) tested positive for chlamydia using the Rapid Chlamydia test, giving an overall test sensitivity of 78 per cent (36/46) for asymptomatic men. The combined sensitivity for symptomatic men testing positive at both sites was higher at 84 per cent.

The majority of participants preferred giving a urine sample (89%), with seven per cent preferring a swab and four per cent willing to provide either. However as participants were not asked to provide a swab, this preference may not be valid. The majority of subjects (96%) indicated that they were willing to wait an hour or more for test results with only four per cent unwilling to wait an hour.

Economic evaluation:

 

Ongoing research:

 

Ongoing or planned HTA:

The rapid Chlamydia test may be of use in rural and remote areas and in public hospital settings. Whether or not this test may be useful for screening populations remains to be ascertained. However, based on initial promising results from studies, the rapid increase in infection rates and the need to reduce the number of new chlamydia infections in the population by identifying asymptomatic individuals HealthPACT have recommended that this technology be monitored for further information in 12-months time.

Web link:

http://www.horizonscanning.gov.au/

References and sources:

Communicable Diseases Australia (2009). National Notifiable Diseases Surveillance System [Internet]. Australian Government Department of Health and Ageing. Available from: http://www9.health.gov.au/cda/Source/CDA-index.cfm [Accessed 12th October].
Ferguson, J. (2005). PCR Testing for Chlamydia [Internet]. Hunter Area Pathology Service. Available from: http://www.haps.nsw.gov.au/Research/PCR_Testing_for_Chlamydia.aspx [Accessed October 9th].
Hocking, J. & Fairley, C. K. (2003). 'Need for screening for genital Chlamydia trachomatis infection in Australia', Aust N Z J Public Health, 27 (1), 80-81.
Hocking, J. S., Willis, J. et al (2006). 'A chlamydia prevalence survey of young women living in Melbourne, Victoria', Sex Health, 3 (4), 235-240.
Mahilum-Tapay, L., Laitila, V. et al (2007). 'New point of care Chlamydia Rapid Test--bridging the gap between diagnosis and treatment: performance evaluation study', BMJ, 335 (7631), 1190-1194.
Morgan, J. (2008). 'Testing and detection trends of Chlamydia trachomatis and Neisseria gonorrhoeae in Waikato, New Zealand: 1998-2006', N Z Med J, 121 (1278), 41-49.
Morgan, J. M. & Bell, A. J. (2009). 'The highs and lows of opportunistic Chlamydia testing; uptake and detection in Waikato, New Zealand', Sex Transm Infect.
Nadala, E. C., Goh, B. T. et al (2009). 'Performance evaluation of a new rapid urine test for chlamydia in men: prospective cohort study', BMJ, 339, b2655.
O'Rourke, K. M., Fairley, C. K. et al (2009). 'Trends in Chlamydia Positivity Over Time Among Women in Melbourne Australia, 2003 to 2007', Sex Transm Dis.
STI Surveillance Team (2009). Laboratory surveillance of Chlamydia and Gonorrhoea in New Zealand, April to June 2009, Institute of Environmental Science and Research Ltd. Available from: http://www.surv.esr.cri.nz/PDF_surveillance/STISurvRpt/2009/STILab2009Q2.pdf
Vajdic, C. M., Middleton, M. et al (2005). 'The prevalence of genital Chlamydia trachomatis in Australia 1997-2004: a systematic review', Sex Health, 2 (3), 169-183.
Walleser, S., Salkeld, G. & Donovan, B. (2006). 'The cost effectiveness of screening for genital Chlamydia trachomatis infection in Australia', Sex Health, 3 (4), 225-234.
Watson, E. J., Templeton, A. et al (2002). 'The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review', J Med Microbiol, 51 (12), 1021-1031.
Wisniewski, C. A., White, J. A. et al (2008). 'Optimal method of collection of first-void urine for diagnosis of Chlamydia trachomatis infection in men', J Clin Microbiol, 46 (4), 1466-1469.

Notes:

The Rapid Chlamydia urine test may be of benefit to rural and remote communities that do not have access to pathology laboratory testing. Although samples for PCR testing can be transported from these communities to regional centres the turnaround time for results is extended. The Rapid Chlamydia urine test enables a rapid diagnosis and a treatment regimen may be put in place immediately without a return visit.