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ournal of Infection and Public Health (2011) 4, 207—210

HORT REPORT

xtensively drug-resistant tuberculosis case in thehames Valley, UK and public health interventions

uhammad Abida,∗, Noel McCarthya, Luisa Saldanaa, Tracey Langhamb,nne McGownb, Christopher Conlonc, Pablo de Vena Franksa

Thames Valley Health Protection Unit, Chilton, Oxfordshire, UKRoyal Berkshire NHS Foundation Trust, Berkshire, UKJohn Warin Ward, The Churchill Hospital, Oxford, UK

eceived 15 April 2011; received in revised form 21 June 2011; accepted 25 June 2011

KEYWORDSExtensivelydrug-resistanttuberculosis;Public health

Summary This study describes the first case of extensively drug-resistant tuber-culosis (XDR-TB) in the Thames Valley and South East Region and discuss the publichealth implications, highlighting the need to integrate current epidemiologicalknowledge with clinical expertise in order to diagnose drug-resistant tuberculosis(TB) early.

The management of the XDR-TB patients is challenging with few treatmentoptions, expensive therapy, side effects of drugs and a longer course of the treat-ment.© 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by ElsevierLtd. All rights reserved.

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ackground

uberculosis (TB) causes 1.7 million deaths eachear worldwide. Multi-drug resistant (MDR) andxtensively drug-resistant tuberculosis (XDR-TB)ave become urgent and worrisome threats to

lobal health. XDR-TB is resistant to both first andecond line anti-tuberculosis therapy. As a result, itan be extremely difficult to treat and is associated

∗ Corresponding author at: Thames Valley Health Protectionnit, Centre for Radiation, Chemical and Environmental Haz-rds, Chilton, Didcot, Oxon OX11 0RQ, UK.el.: +44 845 279 9879; fax: +44 845 279 9881.

E-mail address: muhammad.abid@hpa.org.uk (M. Abid).

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876-0341/$ — see front matter © 2011 King Saud Bin Abdulaziz University for Health

oi:10.1016/j.jiph.2011.06.003

ith a higher mortality than non-resistant strains1], especially in areas with a high prevalence ofIV.

In 2008, 963 XDR-TB cases were reported tohe WHO worldwide [2]. Between 1995 and 2008en XDR-TB cases were reported in the UK, fivef whom died [3]. Of the countries where it haseen reported, XDR-TB is thought to represent, onverage, 5.4% of all MDR-TB cases [2]. However,n Eastern European countries, such as Estonia andithuania, this proportion is much higher (12.5% and4.5% respectively) [2].

This case report describes public health issuesrising from a case of XDR-TB in the Thamesalley.

Sciences. Published by Elsevier Ltd. All rights reserved.

208

Table 1 Timeline of events in the clinical history andmanagement of the case from presentation until XDR-TB diagnosis and subsequent discharge.

Date Event

4th May 08 Presented to A&EMay, June, July 08 Saw GP several times over 3

month period with noimprovement in symptoms

21st August 08 X-ray showed small area ofconsolidation

28th August 08 Acid fast bacilli on microscopy29th August 08 TB treatment started with four

drug regimen (rifampicin,isoniazid, ethambutol andpyrazinamide)—–cultureconfirmed TB shortly after

29th September 08 Resistance to all first main linedrugs reported. Patient wasadmitted to Infectious DiseasesUnit in a negative pressureroom and TB treatmentstopped.

20th October 08 Resistance to streptomycin,kanamycin, moxofloxacin,ofloxacin and p-aminosalicylicacid reported. Re-startedtreatment with clarithromycin,cycloserine, linezolid,protionamide, amikacin andclofozimine

3rd March 09 Discharge from hospitalApril 10 Treatment stoppedFebruary 11 Last reviewed (followed up

every 6 months)

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Discussion

Case investigation and management

Thames Valley Health Protection Unit (TVHPU) wasnotified of a case of TB in August 2008. A 22-year-old student, HIV negative from Lithuania wasinitially treated for pneumonia but later foundto have XDR-TB, the first case in Thames Val-ley and South East Region. The 24-locus VariableNumber Tandem Repeat (VNTR) profile for a cul-ture of Mycobacterium tuberculosis obtained fromthe patient matched with 14 other individualsin the UK, 5 of which were from Lithuania. Nosocial or epidemiological ink was established withthe other cases. After five months of hospital-ization, the patient was discharged to continuetreatment at home, completing 16 months of theplanned two years of treatment due to intolera-

ble side effects. The patient has had six monthlyfollowup appointments and has had no progres-sion of disease. The clinical details of the case

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M. Abid et al.

ere published as a case report in the British Med-cal Journal [4] and are outlined in the timelineTable 1).

ublic health interventions (s)

ommunication

TB incident control team was arranged shortlyfter the diagnosis of XDR-TB, to discuss con-act tracing and screening. Guidance was soughtrom the National MDR-TB Clinical Advice Ser-ice [5], which helps clinicians implement theost effective treatment. The public health

uthorities provide a useful communications linky ensuring clinicians are aware of this ser-ice from the moment a case of MDR-TB isotified.

Other Health Protection Units nearby were con-acted to identify potential links with other cases.

ontact tracing and screening

he TB nurse arranged contact tracing follow-ng initial TB diagnosis. Five close contacts werecreened using Mantoux testing, Interferon gammassay and a chest radiograph. Only one positiveontact was identified who was asymptomatic. UKational guidelines on tuberculosis [6] were fol-

owed to manage this contact; no chemoprophylaxisas given, yearly follow up was arranged anddvice was given to contact TB services immedi-tely if any symptoms suggestive of TB develop.his contact has remained asymptomatic and is inontact with the TB nurse. Public health adviceas also given to the patient’s place of worknd study in order to identify other potentialontacts.

A relative who had stayed with the patient in theK while the patient had been symptomatic and hadince returned to Lithuania was later identified asn additional contact. Direct contact with the rela-ive was not possible, but the patient was asked todvise the relative to be screened locally. The rel-tive was a medical student and the public healthuthorities in Lithuania were informed. This con-act had no respiratory symptoms and there wereo abnormal changes on the chest X-ray.

DR-TB exists in Europe and 149 cases of XDR-TBere reported during 2003—2007, the majority of

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case of XDR-TB in the UK

hich were from East European countries (58 werestonia; 53 from Latvia and 25 from Lithuania) [7].n the UK 10 cases of XDR-TB were reported inhe period of 1995—2008 [3]. Increasing migrationithin the European Union and worldwide will cer-

ainly see these numbers rise in low risk countriesuch as UK.

The Eastern European background of this patienteflects epidemiological trends in drug-resistant TBnd could have alerted clinicians earlier to theossibility of XDR-TB. Current NICE guidelines [6],owever, do not specifically highlight the risk ofrug-resistant TB in patients from countries, such asithuania, where there is a relatively low incidencef TB overall, but a high proportion of MDR/XDR-TBases. Future UK cases of XDR-TB may have similaremographic profiles and guidelines in managementould be reviewed to include this epidemiologicalnowledge.

This case illustrates some of the difficultiesncountered when tracing contacts living out-ide the UK, raising the question of how faro go when investigating the source of infec-ion. There is a need for agreements betweenther national authorities to overcome these prob-ems.

Successful management of XDR-TB relies uponrompt diagnosis, notification and treatment ofases, a problem with TB generally. This patientemained symptomatic for three months beforeffective treatment was started, allowing pro-onged exposure to contacts and increasing theisk of a potential outbreak. Concerns were raisedegarding the delay in diagnosis of this case andhe speed of the laboratory diagnostic tests. Theputum culture on this case did not grow veryell which delayed the drug susceptibility test-

ng (DST) for the first and second line drugs. DSTs done as a twostage process initially for first-ine drugs and then for secondline drugs. Testing

wider panel early when drug resistance is sus-ected would increase the speed of reporting. Thenfectious Diseases Unit involved in this case nowast-tracks all smear positive sputum samples tohe reference laboratory for rapid drug sensitivityesting.

After diagnosis, strict monitoring of treat-ent is essential to ensure successful outcomes.he patient started directly observed therapyDOT) in hospital, but was trained to self-dminister medication prior to discharge, makingt difficult to ensure 100% adherence. National

uidelines recommend DOT for treating MDR andDR-TB cases but its enforcement can be diffi-ult.

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At present, cases of XDR-TB are expected to beporadic, however, a single outbreak could leado XDR-TB being established within the UK pop-lation or sub-population. The resources neededo manage this case were substantial, includingosts of clinical care, expensive anti-TB medica-ions, work load of contact tracing and followp.

onclusion

DR-TB has a high mortality rate and is a signif-cant public health threat. Highlighting patientsrom countries with a high proportion of MDR-B and expediting drug susceptibility testing inhese patients would aid more rapid diagnosis.fficient contact tracing, resource managementnd strict adherence to medication, will all bessential in the successful prevention of futureases.

onflict of interest statement

unding: No funding sources.ompeting interests: None declared.thical approval: Not required.

cknowledgments

rof. Francis Drobniewski and his team athe National Mycobacterium Reference Unit,ondon.

Jonh Warin Ward staff at The Churchill Hospital,xford.

eferences

1] Kim DH, Kim HJ, Park SK, Kong SJ, Kim JS, Kim TH, et al.Treatment outcomes and long-term survival in patients withextensively drug-resistant tuberculosis. Am J Respir Crit CareMed 2008;178(10):1075—82.

2] Multidrug and extensively drug-resistant TB (M/XDR-TB):2010 global report on surveillance and response. Geneva:World Health Organization; 2010, http://whqlibdoc.who.int/publications/2010/9789241599191 eng.pdf.

3] Tuberculosis in the UK: annual report on tuberculosis surveil-lance in the UK 2009. London: Health Protection Agency,Centre of Infections; December 2009.

4] Moran E, McGown A, Conlon C. Case report: persistent Balticcough. BMJ 2010;341:511, 7771.

5] National MDR-TB Clinical Advice Service. Tuberculo-sis update. Health Protection Agency; March 2011,

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http://www.hpa.org.uk/web/HPAwebFile/HPAweb C/1296-

683847254.

[6] NICE. Tuberculosis: clinical diagnosis and management oftuberculosis, and measures for its prevention and control.Royal College of Physicians; 2006.

Available online at www.s

M. Abid et al.

7] Devaux I, Manissero D, Fernandez de la Hoz K, Kremer

K, van Soolingen D. Surveillance of extensively drug-resistant tuberculosis in Europe, 2003—2007. Euro Surveill2010;15(11), pii = 19518 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19518.

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