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Volume 2 No 14; 04 April 2008

 

 

High-level azithromycin resistance in Neisseria gonorrhoeae

The HPA, through the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP), has detected a cluster of gonococcal isolates that exhibit high-level resistance to azithromycin, an antimicrobial agent used for treatment of chlamydial infections.

The Department of Health has issued an alert to microbiologists to inform appropriate testing [1].

Nevertheless, clinicians are reminded that resistance in Chlamydia trachomatis is unknown and that azithromycin remains an effective treatment for chlamydial infections, although it is not appropriate for the treatment of gonnorrhoea.

Background

Azithromycin (1g, single dose) is a recommended therapy for chlamydial infections. It also has activity against Neisseria gonorrhoeae and Treponema pallidum but is not a recommended therapy for gonorrhoea because the 1g dose gives inadequate cure rates (93%) and a 2g dose, which is effective, is not well tolerated.

However, dual infections with both C. trachomatis and N. gonorrhoeae are common and there is a likelihood that azithromycin will be used, at the lower dose, in cases where only the chlamydial infection is diagnosed and the presence of gonococci is not recognized, both in genitourinary medicine (GUM) clinics and in primary care settings.

The GRASP (The Gonococcal Resistance to Antimicrobials Surveillance Programme) has monitored the susceptibility of gonococci to azithromycin since 2001, aiming to detect the emergence and spread of resistance. Resistance is currently defined as a minimum inhibitory concentration (MIC) >0.5 mg/L, although good data on the relationship of MICs to therapeutic failure are limited.

GRASP has shown that:

  • Low-level azithromycin resistance has increased annually between 2001 and 2006, reaching 2.2% nationally in 2005 and over 5% in some regions of England and Wales ; the highest MIC observed was 12 mg/L.
  • In 2007, high-level resistance to azithromycin (MIC 4096 mg/L) was detected in six isolates of N. gonorrhoeae . These were all from heterosexual patients, and showed similar resistance profiles, being susceptible to first-line treatments for gonorrhoea.
  • Azithromycin use was not documented in any of these patients.
  • Five of the six isolates were referred from a single laboratory in the Liverpool area, while the remaining isolate was recovered in Cardiff. All six isolates were identical (ST649) by sequence-based typing (NG-MAST), suggesting an outbreak in the heterosexual community.
  • Further highly-resistant isolates have been identified in Scotland, but high-level azithromycin resistance has not been documented elsewhere in the world.
  • Low-level azithromycin resistance in N. gonorrhoeae can be mediated by various mechanisms. The mechanism of this high-level resistance is currently unknown and could be novel, or a combination of known mechanisms.
  • In line with national guidelines the majority of patients in GRASP were also treated for chlamydial infection and the proportion who received azithromycin therapy for this has increased substantially, from <5% in 2000 to 40.1% in 2006

The resistance alert issued by Department of Health [1] recommends the following:

  • Azithromycin should not be used to treat gonorrhoea
  • Patients treated with azithromycin or doxycycline for chlamydia cannot be assumed to have been adequately treated for gonococcal infection. Gonorrhoea should be treated specifically, according to therapeutic guidelines, at the same time as chlamydia is treated.
  • All clinical laboratories should test N. gonorrhoeae isolates for resistance to a panel of antimicrobials comprising:
      • both recommended first line therapies for gonorrhoea (ceftriaxone or cefixime),
      • azithromycin (and tetracycline if used locally to treat chlamydia co-infections).
      • any other agents used locally to treat gonorrhoea (e.g. ciprofloxacin or penicillin).
  • Where azithromycin resistance is detected a report should be sent to the clinician stating "Resistance has been detected to azithromycin. Specific anti-gonococcal therapy should always be used to treat cases of gonorrhoea"
  • All possible examples of resistance to azithromycin (zone of inhibition ≤ 27mm, using a 15 µg disc) or to cefixime or ceftriaxone should be referred to the Sexually Transmitted Bacteria Reference Laboratory for confirmation, as interpretation can sometimes be difficult.

References
1. Inspector of Microbiology and Infection Control. High-level azithromycin resistance in Neisseria gonorrhoeae. DH Gateway ref 9698, 4 April 2008. Available at
http://www.dh.gov.uk/en/Publichealth/Patientsafety/Microbiologyandinfectioncontrol/DH_075723

Hepatitis E in passengers on a cruise ship

Four cases of hepatitis E infection were reported among elderly male passengers on a round-the-world cruise between January 7 and March 28, 2008. The dates of onset were between 12 and 23 March and it is thought highly likely that exposure occurred at some point during the cruise. There were a number of ports of call including: Madeira, Barbados, Acapulco, San Francisco, Pago Pago (American Samoa), Nuku'Alofa (Tonga), Auckland, Sydney and Hong Kong.

The passenger capacity of the cruise ship is 1800 with 900 staff but, as people joined and left the cruise at different points during the journey, the cumulative number of passengers on board at some point during the cruise was 3000. Passengers were mainly from the UK but also included nationals from the USA, Australia, South Africa, Denmark, and Ireland .

The Health Protection Agency (HPA) has been working closely with the cruise ship operator and port health authority to assist with investigations and ensure all passengers receive appropriate information. The cruise company has sent letters and a factsheet on hepatitis E to all passengers to inform them and to advise that they seek medical advice should they develop symptoms compatible with hepatitis E. They are also being asked to contact the HPA directly so that linked cases might be identified.

Hepatitis E is a viral infection that usually produces mild disease with symptoms of jaundice, dark urine and pale stools with or without nausea, loss of appetite and/or abdominal pain [1]. In rare cases it can prove fatal, particularly in pregnant women. Hepatitis E is endemic in many countries in Asia, Africa and Central America. It is a relatively uncommon cause of hepatitis in the United Kingdom; there were 292 cases reported in 2006 and the majority of these were travel associated.

Direct person-to-person spread of hepatitis E is uncommon. Exposure usually arises from contaminated food or water and can be prevented through good hygiene, for example:

  • Drinking bottled water only if it is from a known safe supply and the bottle is unopened.
  • Not using ice or eating anything with ice, unless the ice is made from safe bottled water.
  • Not eating uncooked fruits or vegetables unless peeled and washed in safe water
  • Not eating foods or beverages from street vendors.

The HPA asks health professionals to ensure that any patients with symptoms compatible with hepatitis E are tested. Samples (10ml EDTA whole blood) should be sent to the Virus Reference Department (VRD), HPA Centre for Infections, 61 Colindale Avenue, London, NW9, 5HT [2].

Enquiries should be directed to email: zoonoses@hpa.org.uk

References
1.http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1191942127585?
p=1191942127585

2. Further advice on testing can be sought from VRD's Blood Borne Viruses Unit. Tel: 020 8327 6204, http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1200660013228?
p=1200660013228.

Guidance on the application of dose coefficients for the embryo, fetus and the breastfed infant in dose assessments for members of the public

International Commission on Radiological Protection (ICRP) recommendations on assessment of risk to the public from radionuclides in the environment [1, 2] assume that in most situations an explicit assessment of the dose to either the embryo/foetus or the breastfed infant is not required. However, for some radionuclides - principally isotopes of phospohorus and the alkaline-earth elements (calcium, strontium, etc) - it is necessary for special consideration to be given to the foetus/breast-fed infant where these materials form a significant part of any release of radioactivity to the environment. (In these cases the dose due to in utero exposure and breastfeeding can be effectively significantly higher than that received by the mother.)

A new HPA publication [3] provides guidance on the application - where such radionuclides are involved - of ICRP dose coefficients which, for other materials, would be sufficient for risk assessing, without special consideration of in utero exposures or transfer of radionuclides in breast milk. The application of these coefficients in relation to situations of routine exposure, accidents and emergencies are considered.

References

1. ICRP. Doses to the embryo and fetus from intakes of radionuclides by the mother. ICRP publication 88. Ann ICRP 2001, 31 (1-3).

2. ICRP (2004). Doses to infants from ingestion of radionuclides in mothers' milk.

3. Guidance on the application of dose coefficients for the embryo, foetus and the breastfed infant in dose assessments for members of the public . Documents of the Health Protection Agency. Radiation, Chemical and Environmental Hazards, RCE-5, March 2008. ISBN 978-0-85951-614-3. Printed copy, £21 + 10% postage and packing, available from CRCE Information Office, tel: 01235 822742/822603; email: chiltoninformationoffice@hpa.org.uk. Available to download free from the HPA website: http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1207121671073?p=1199451989432

World Health Day

'Protecting health from climate change' is the theme of World Health Day, 7 April 2008, which also marks the 60th anniversary of the founding of World Health Organization. A dedicated website provides details of co-ordinated activities and related documentation [1].

The climate change theme builds on the WHO's 2003 report on the subject, Climate change and human health - risks and responses [2]. More recently an HPA report considered the public health implications of climate change for the UK [3].

References
1. http://www.who.int/world-health-day/en/index.html

2. http://www.who.int/globalchange/climate/summary/en/index.html

3. Health effects of climate change in the UK. London: Department of Health and the Health Protection Agency. February 2008. See, HPA report on climate change and health, HPR Vol. 2 No. 7, 15 February 2008.