1. Perils of medical tourism
Dr Theo Gouliouris
Microbiology and Infectious Diseases StR
Addenbrooke’s Hospital, Cambridge

2. Case history 55 year old man, Pakistani origin
ESRD secondary to hypertensive nephrosclerosis
2007 Haemodialysis via AV fistula
2009 Transplant waiting list

3. Case history Summer 2010 Travelled to Pakistan
August 2010 HCV antibody and PCR positive
Removed from transplant waiting list pending antiviral therapy
September 2010 commenced on ribavirin 200 mg daily
October 2010 travelled to Pakistan against medical advice

4. Acute presentation May 2011 Presented to Addenbrooke’s unwell
Living-related kidney transplant in Pakistan Nov 2010
Donor and HLA match unclear
Recipient CMV positive
Complications
ARDS, ventilated in ICU for 4 days
Wound dehiscence and infected perinephric haematoma, treated with imipenem and colistin
Poor graft function: creatinine 477 mol/L
Medications: Prednisolone 10mg od, Tacrolimus 3mg/4mg, Mycophenolic acid 720mg bd
Letter said wound healed. Patient believes kidney working well.

5. Examination Vomiting Febrile T 38.9°C Tachycardia
Widespread vesicular rash consistent with shingles
Open wound in right iliac fossa, packed, discharging pus
Commenced on empirical piperacillin-tazobactam and aciclovir
Barrier nursed

6. Baseline investigations
Blood test
Result
Normal range
Urea
19.9
mmol/l
Creatinine
398
mol/l
Albumin 29
30-51 g/l
ALP
145
U/l
ALT 6
0-50 U/l
Bilirubin
0-17 mol/l
CRP 59
0-6 mg/l
WCC
6.8
x109/l
Neutrophils
6.3
x109/l
Lymphocytes
0.26
x109/l
Haemoglobin
8.8
g/dl
Platelets
258
x109/l PT
13.4 s

7. CT abdomen and pelvis
CT abdomen showed an intraparenchymal abscess lower pole of kidney communicating with perinephric abscess. Multiple intramuscular abscesses R flank and R abdominal muscle.

8. Management and progress
Ultrasound-guided drainage of 3 largest collections
Clinical deterioration
Ongoing fever
Productive cough
CXR pulmonary infiltrates
Metabolic acidosis
Diarrhoea
Mycophenolate and tacrolimus stopped
Transplant nephrectomy 12 days post-admission

9. Microbiology / virology results
Skin vesicles: VZV DNA detected
Blood: Low-grade CMV viraemia
Stool: Norovirus detected
Wound swabs:
Multidrug-resistant ESBL-producing Klebsiella pneumoniae and E. coli
vancomycin-resistant Enterococcus faecium
Peri-nephric abscess aspirates
Filamentous mould - Aspergillus terreus (amphotericin B resistant)
Meropenem-resistant Klebsiella pneumoniae

10. Klebsiella pneumoniae antibiogram
Antimicrobial
MIC (mg/l)
S/I/R
Breakpoint
Ampicillin
>64 R 8
Amoxillin/Clavulanate 64
Cefotaxime
>256
1-2
Ceftazidime
1-8
Ertapenem
>16
0.5-1
Imipenem 16
2-8
Meropenem
Aztreonam
Not done
2-4
Piperacillin/Tazobactam
Colistin 32 2
Ciprofloxacin
>8
Gentamicin 1 S
8-16
Amikacin
Tobramycin 4 I
Tigecycline
0.5
Fosfomycin
(32)

11. Real-time PCR detection of New Delhi metallo- beta-lactamase
Purple - control NDM positive extract DNA
Green - clinical isolate extract DNA
Black/blue - PCR negative control isolates
Courtesy of R. Swayne and M.Ellington, Cambridge HPA

12. Histopathology results
Numerous branching septal hyphae invading vessel walls and in necrotic parenchyma. Balls of fungal hyphae.

13. GII.4 – Most prevalent norovirus in humans
GIV Cluster
GII.4 – Most prevalent norovirus in humans
GI Cluster
Partial sequencing of capsid encoding region - genogroup 1 genotype 4
GII Cluster
Adapted from Glass et al. Norovirus Gastroenteritis. N Engl J Med 2009;361:1776
Courtesy of M. Curran, Cambridge HPA

14. Further management Recurrent collections requiring drainage procedures
Antimicrobial therapy complex – renal impairment, drug interactions and toxicity, multiple MDR organisms, need for prolonged treatment
Long courses of tigecycline (63d), amikacin (45d) and voriconazole

15. Transplant tourism Common
5 to 10% of kidney transplants performed worldwide
Pakistan 2006: 2/3 of 2000 transplants for foreign recipients1
Ethical issues
Organ trafficking
Transplant commercialism
Declaration of Istanbul on Organ Trafficking and Transplant Tourism, 2008
Ethical issues: equity, justice, respect for human dignity
Summit meeting of 150 representatives of scientific and medical bodies from around the world, govt officials, social scientists and ethicists
1. Naqvi et al, Transpl Int 2007; 20: 934

16. Literature review of outcomes
21 case series between 1990 and 2012
Total no. of patients 1331 (range 5 – 515)
Countries: India (62%), Pakistan (13%), China (12%), Philippines (3%), Egypt (3%), Iran
Graft 1-yr survival rate 86.9% (range %)
Patient 1-yr survival rate 91.9% (range %)
Acute rejection common 23.4% (range 10-50%)

17. Infective complications
Infections common, esp. CMV, wound infections
Significant risk of BBV acquisition
HIV 0.8%
HBV 4%
HCV 16%
Risk of TB 3%
Malaria reported (1.8%)
Little emphasis on resistant organisms (mainly ESBL producing Enterobacteriaceae, one panresistant Acinetobacter baumannii)

18. Aspergillus infections in renal transplants
1.3% one-year cumulative incidence of invasive fungal infections in renal transplants1
14% of IFI caused by Aspergillus spp. (<5% A. terreus)
Usually pulmonary or disseminated infection
Recognised association with transplant tourism2
17 cases identified
Infection in transplanted graft 35%
Graft loss or death 76%
TRANSNET 1500 patient American cohort
Pappas et al, CID 2010; 50: 1101
Shoham et al, Transplant ID 2010; 12: 371

19. Outcome Discharged from hospital on day 82
Last clinical review: wound completely healed, incisional hernia
HCV RNA negative

20. Conclusions
Transplant tourism is associated with significant morbidity and mortality, particularly related to infection
NDM-1 producers, pose a significant risk to patients who travel to the Indian subcontinent for medical treatment
Patients returning following hospitalisation in endemic countries should be screened for the presence of resistant bacteria and isolated
Rapid molecular detection methods for antimicrobial resistance facilitate prompt diagnosis

21. Acknowledgments
Dr S.H. Aliyu, Dr S. Ojha, Prof S. J. Peacock, Dr M.E. Török
Renal Transplant team
Microbiology and Infectious Diseases colleagues
Dr Matthew Ellington, Dr Rosie Swayne (Cambridge HPA)
Dr Martin Curran (Cambridge HPA)
Dr Verena Broecker (Histopathology Department)
Dr Winterbottom (Radiology Department)