Journal of Hospital Infection 87 (2014) 241e244

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Journal of Hospital Infection

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Short report

Tuberculosis screening in a dialysis unit: detecting

latent tuberculosis infection is only half the problem
S.O. Brij, S.C. Beck, F. Kleemann, A.L. Jack, C. Wilkinson, D.A. Enoch*
Peterborough & Stamford Hospitals NHS Foundation Trust, Peterborough City Hospital, Peterborough, UK

A R T I C L E I N F O S U M M A R Y

Article history: Patients with chronic kidney disease are at increased risk of tuberculosis. We describe the
Received 12 February 2014 events that occurred when we encountered a patient receiving haemodialysis with pul-
Accepted 27 May 2014 monary tuberculosis. Nine (of 41) patients dialysing at the same time as the index case had
Available online 24 June 2014 a positive interferon-gamma release assay (IGRA) and were offered therapy for latent
tuberculosis infection (LTBI). Patients with an initial negative IGRA were rescreened at six
Keywords: months, identifying a further three IGRA-positive patients. All patients were then
Dialysis rescreened at 12 months. No new IGRA-positive cases were identified and no staff or
Interferon-gamma release assay patients developed active disease. Only five of the 12 IGRA-positive patients completed
Tuberculosis LTBI therapy.
ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction Events leading to the investigation

Patients with chronic kidney disease (CKD) are at increased
risk of developing tuberculosis, which may be due to altered
T-cell immunity or to immunosuppressive therapy.1 The prev-
alence of CKD is also higher in ethnic minority groups at
increased risk of latent tuberculosis infection (LTBI).2
Evidence to guide protocols for active case-finding and
treatment of LTBI in haemodialysis patients is limited.2 This
report describes the events that occurred on encountering a
clinical case of tuberculosis in a patient receiving
haemodialysis.
* Corresponding author. Address: Clinical Microbiology & Public
Health Laboratory, Public Health England, Addenbrooke’s Hospital,
Cambridge CB2 2QW, UK. Tel.: þ44 (0)1223 257035; fax: þ44 (0)1223
242775.
E-mail address: David.enoch@addenbrookes.nhs.uk (D.A. Enoch).
Hospital setting
Peterborough City Hospital is a general hospital with 612
beds. The hospital hosts a satellite dialysis unit run by Leicester
Hospitals with 15 stations and two side-rooms. The unit oper-
ates MondayeSaturday with three shifts per day.
Index case
A 56-year-old man from India arrived in the UK in April 2011.
He had a background of haemodialysis-dependent CKD sec-
ondary to systemic lupus erythematosus and initially dialysed
in London. In July 2011 he relocated to Peterborough and dia-
lysed in Corby until December 2011 when he transferred to
Peterborough. He dialysed three times per week for an average
of 4 hours per episode. He was seen in the respiratory clinic
following a positive interferon-gamma release assay (IGRA) test
performed while investigating weight loss. Computed

http://dx.doi.org/10.1016/j.jhin.2014.05.008
0195-6701/ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
242 S.O. Brij et al. / Journal of Hospital Infection 87 (2014) 241e244
tomography (CT) thorax/abdomen was unremarkable. Echo-
cardiography revealed an ejection fraction of <30%. His weight
loss was thought to reflect cardiac cachexia and improving fluid
balance. He was reviewed in December 2011 and clinically and
radiologically there was no evidence of tuberculosis. By
February 2012 he had achieved euvolaemia and was clinically
improving.
In May 2012 he presented with a productive cough and
breathlessness. He had not been noted as actively coughing
while on the dialysis unit. He denied night sweats but was
febrile (38.9 C) with respiratory crackles on examination. In-
flammatory markers were raised. Chest radiography revealed
new bilateral upper lobe infiltrates. He was admitted for
intravenous co-amoxiclav but failed to improve. A respiratory
opinion was sought six days after admission: tuberculosis was
suspected. Transfer from a four-bedded bay to respiratory
isolation was suggested. Sputum was sent and was acid-fast
bacilli (AFB) smear positive (day 1), and nucleic acid amplifi-
cation test (NAAT) for tuberculosis was positive the following
day.
He was commenced on anti-tuberculous therapy (ATT).
High-resolution CT thorax confirmed bilateral upper lobe
cavitating lesions. Mycobacteria were detected on day 14,
confirmed as Mycobacterium tuberculosis at day 38 and fully
susceptible tuberculosis (mycobacterial reference laboratory)
at day 81. He completed six months of standard ATT and re-
mains well 12 months after stopping therapy.
A contact-tracing meeting was convened involving staff
from Peterborough and Leicester Hospitals and the Health
Protection Agency (HPA).
Bacteriology methods
Samples for tuberculosis are stained for AFB using auramine
stain and cultured using the Bactec MGIT960 Mycobacterial
Detection System (Becton Dickinson, Franklin Lakes, NJ, USA).
Smear-positive samples are subjected to NAAT for detection of
M. tuberculosis (GeneXpert, Cepheid, Sunnyvale, CA, USA).
IGRAs are performed using QuantiFERON-TB Gold (QFT-GIT;
Cellestis, Chadstone, Victoria, Australia).
Infection control measures
Patients with suspected pulmonary tuberculosis are placed
in source isolation and FFP3 masks are made available for
staff.3
Results
Actions taken by the contact-tracing committee
(Table I)
Identification of exposed/ward patients
Six patients were identified who spent 8 h with the index
case in the ward prior to him being isolated. Letters were sent
to these patients and their general practitioners (GPs) to
inform them of possible exposure.3
Advice to staff
All ward and haemodialysis staff members were advised by
letter of possible exposure and to seek medical attention if
they had any features of active tuberculosis. Pregnant staff
members were advised not to attend the index case while he
was considered contagious.
Staff were not offered screening with IGRA testing. Only one
member of staff contacted the community tuberculosis team.
Their symptoms were not suggestive of active tuberculosis but
screening was undertaken (chest X-ray and Mantoux as per
local policy) and found to be negative. The community tuber-
culosis team screened six household contacts as per UK
guidelines.3 One child was offered treatment for LTBI.
Screening haemodialysis patients
The index case was considered unlikely to have been in-
fectious in Corby when he had a normal CT scan.
Identification of at-risk members of the public
The HPA contacted the drivers who transported the index
case to hospital for haemodialysis, and wrote to their GPs
advising of possible exposure.
Results of contact screening
Fifteen patients received haemodialysis in the same session
as the index case since the index case commenced haemodialysis
in Peterborough, one of whom had been transferred for trans-
plantation. Dialysis patients within Peterborough typically spend
5e6 hours per session on the unit from arrival until discharge.
Twelve patients underwent IGRA testing and a chest X-ray. Two
of these had positive IGRA tests (one an Indian-born Asian, the
other a UK-born Caucasian). Three patients were not screened;
one of these underwent transplantation, and two died prior to
testing of end-stage kidney disease.
At the following contact-tracing meeting, screening was
extended to all patients dialysing on the same day as the index
case, identifying a further 26 patients. Two of these had died
(from non-tuberculosis-related causes) and two transplant re-
cipients had been transferred. Seven of the remaining 22 pa-
tients screened (12 weeks after smear positivity) were IGRA
positive (five UK-born Caucasians; two Asians born in India and
Pakistan respectively). Seven abnormal chest X-rays were
reviewed but tuberculosis was not suspected or diagnosed in
any patient. All nine were offered ATT for LTBI; only five
completed therapy.
Repeat IGRA and chest X-ray (or CT) screening were per-
formed six months later on the 27 patients with negative IGRA.
Three patients tested IGRA positive (two UK-born Caucasians
and one Asian born in Pakistan) and were offered ATT for LTBI;
one completed therapy.
A final screen was conducted 12 months after smear posi-
tivity of all exposed patients. No further IGRA-reactive patients
were detected and no contacts developed symptoms of active
tuberculosis in this time. Seven of the nine patients positive on
first screen were rescreened at 12 months; four were negative.
Further investigation of these four patients suggested that they
had IGRA levels between 0.35 and 0.91 IU/mL. Those that
remained positive had IFN-g concentrations >3 IU/mL.
Financial and clinical impact
Overall, 91 IGRA tests (at w£70 each; totalling £6370), 103
chest radiographs (w£27; £2,781) and three CT chests (w£82;
£246) were performed (requiring interpretation). Eleven
 S.O. Brij et al. / Journal of Hospital Infection 87 (2014) 241e244 243

Table I
Actions implemented and timeline
Time Action Results
June 2012 Contact-tracing on ward Six patients identified in the bay
e UK guidelines state that there is only a potential risk
of infection if they have had continuous contact for
more than an 8 h period in the same bay.3
e A standard letter (as per NICE guidelines) was sent
to them to advise them of the potential contact with a
patient with active tuberculosis. The letter advised that
no further action is required unless they became unwell.
Copies of the letters were sent to the patients’ GPs.3
e It was agreed that the staff would receive the same
letter, which was copied to their GP and to the
hospitals’ occupational health department.
July 2012 Contact-tracing on haemodialysis unit Fifteen patients identified in the haemodialysis
e Patients who dialyse in the same session would be unit
screened using chest X-ray and IGRA testing. e Two IGRA þve (and started on latent
e Treatment for latent tuberculosis would be considered tuberculosis therapy)
for patients with a positive IGRA. e Ten IGRA ve (two of these with abnormal
e Further imaging (e.g. CT) would be considered for chest X-ray)
patients with abnormal chest X-ray. e Two died and one transplanted
Contact-tracing on haemodialysis unit Twenty-six further patients identified and
e Screening was extended to patients who dialyse in the screened
same day using chest X-ray and IGRA testing. e Seven IGRA þve (and started on latent
tuberculosis therapy)
e Seventeen IGRA ve (one with abnormal CT)
e Two transplanted prior to testing
Press statement drafted
Report as a serious incident to the PCT
December 2012 Contact-tracing on haemodialysis unit Twenty-seven retested with IGRA and chest
e Patients who dialyse in the same day with a previously X-ray
negative IGRA test would be screened using chest X-ray e Three further patients IGRA þve
and IGRA testing
July 2013 Contact-tracing on haemodialysis unit All patients retested
e All patients previously tested would be screened using e No further positive cases identified
chest X-ray and IGRA testing
NICE, National Institute for Health and Clinical Excellence; GP, general practitioner; IGRA, interferon-gamma release assay; PCT, Primary
Care Trust.

courses of LTBI therapy were administered (w£90; two tablets
of Rifinah 300 once daily and pyridoxine 10 mg (once daily;
£990)) and 32 extra outpatient consultations were required (at
w£200 per consultation; £6,400), yielding an approximate total
cost of at least £16,787.
Discussion
We describe an isolated case of smear-positive pulmonary
tuberculosis in a haemodialysis patient, the measures taken to
reduce the risk of nosocomial transmission, and some of the
costs incurred. A multidisciplinary team was set up to consider
the ill-defined period of infectivity, screening (who, how,
when), whether to treat, and to co-ordinate patient and staff
information.
Tuberculosis outbreaks are well described, and have often
been due to healthcare workers and other patients.4,5 Previous
outbreaks have used tuberculin skin testing (TST) and chest
X-ray.4,5 Recent studies suggest that IGRA testing is superior to
TST.6,7
Serial IGRA testing has only been assessed in small cohorts of
patients. Seroconversion/seroreversion is not uncommon.8
Three patients converted from IGRA negative to positive at
six months, all with low concentrations of interferon-gamma
(IFN-g) (<1.50 IU/mL). In our cohort, persistently positive
IGRA was found to occur in patients with higher concentrations
of IFN-g. Those who displayed reversion had lower concentra-
tion reactions (<1.50 IU/mL), suggesting that discrepancies in
serial IGRA testing are increased at low concentrations, as
described previously.8 The clinical significance of reversions is
uncertain. Variations in host immunity and transient responses
to infection, reproducibility of the QFT-GIT assay and use of a
single cut-off value are likely to be contributory factors;
however, without a gold standard LTBI diagnostic test,
distinction between true- and false-positive results cannot be
determined. A study of healthcare workers who underwent
serial QFT-GIT testing concluded that adding a borderline zone
(0.35e2.0 IU/mL) would aid interpretation.9 Our limited data
support this.
There was an opportunity to treat the index case when he
had LTBI and no clinical or radiological evidence of pulmonary
244 S.O. Brij et al. / Journal of Hospital Infection 87 (2014) 241e244
tuberculosis. However, in this group of patients, successful
completion of ATT for latent therapy was low (5/9; 55.6%)
despite high patient anxiety in the setting of a potential
outbreak. Patient selection and when to screen for latent
tuberculosis in the course of advanced CKD remains
challenging.
A risk assessment was undertaken by the contact-tracing
meeting regarding screening staff members. It was felt that the
amount of contact with the index case was highly variable but it
was crudely estimated that 16 dialysis nurses spent between 20
and 260 min in close clinical contact with the index case prior to
barrier nursing being undertaken. A decision was made that
potentially exposed staff members would not be formally
screened, especially as the initial screening of close contacts
revealed latency in only one of the index case’s children.
We provide approximate costs for each aspect of the
investigation, which totalled more than £16,000. Clearly there
are further costs not included in this estimate (discussions with
patients/relatives, meetings, teleconferences, writing re-
ports, etc.).
IGRA and chest X-ray are appropriate tools to screen for LTBI
in a haemodialysis population. A multidisciplinary approach is
essential to co-ordinate actions. In our experience, treatment
for LTBI is poorly tolerated in haemodialysis patients. Further
work is required to determine more accurately who requires
screening and the timing thereof.
Acknowledgements
We thank Dr D. Jenkins of University Hospitals Leicester NHS
Trust and Dr K. King of Public Health England for their help
during this episode.
Conflict of interest statement
None declared.
Funding sources
None.
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