Download Perils of medical tourism

Perils of medical tourism
Dr Theo Gouliouris
Microbiology and Infectious Diseases StR
Addenbrooke’s Hospital, Cambridge
Case history
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55 year old man, Pakistani origin
ESRD secondary to hypertensive nephrosclerosis
2007 Haemodialysis via AV fistula
2009 Transplant waiting list
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
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
Examination
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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
Baseline investigations
Blood test
Result
Normal range
Urea
19.9
0.0-7.5 mmol/l
Creatinine
398
35-125 mol/l
Albumin
29
30-51 g/l
ALP
145
30-135 U/l
ALT
6
0-50 U/l
Bilirubin
6
0-17 mol/l
CRP
59
0-6 mg/l
WCC
6.8
4.0-11.0x109/l
Neutrophils
6.3
2.0-8.0x109/l
Lymphocytes
0.26
1.0-4.5x109/l
Haemoglobin
8.8
g/dl
Platelets
258
150-400x109/l
PT
13.4
9.8-12.6 s
CT abdomen and pelvis
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
Microbiology / virology results
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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
Klebsiella pneumoniae antibiogram
Antimicrobial
MIC (mg/l)
S/I/R
Breakpoint
Ampicillin
>64
R
8
Amoxillin/Clavulanate
64
R
8
Cefotaxime
>256
R
1-2
Ceftazidime
>256
R
1-8
Ertapenem
>16
R
0.5-1
Imipenem
16
R
2-8
Meropenem
16
R
2-8
Aztreonam
Not done
R
2-4
Piperacillin/Tazobactam
>64
R
16
Colistin
32
R
2
Ciprofloxacin
>8
R
0.5-1
Gentamicin
1
S
8-16
Amikacin
2
S
8-16
Tobramycin
4
I
2-4
Tigecycline
0.5
S
1-2
Fosfomycin
4
S
(32)
Real-time PCR detection of New Delhi metallo- beta-lactamase
0.6
0.5
0.4
0.3
0.2
0.1
0.0
5
10
20
15
25
30
35
Cycle
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
Histopathology results
GIV Cluster
GII.4 –
Most
prevalent
norovirus
in humans
GI
Cluster
GII Cluster
Adapted from Glass et al. Norovirus Gastroenteritis. N Engl J Med 2009;361:1776
Courtesy of M. Curran, Cambridge HPA
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
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
1. Naqvi et al, Transpl Int 2007; 20: 934
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 60-100%)
• Patient 1-yr survival rate 91.9% (range 68-100%)
• Acute rejection common 23.4% (range 10-50%)
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)
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%
1.
2.
Pappas et al, CID 2010; 50: 1101
Shoham et al, Transplant ID 2010; 12: 371
Outcome
• Discharged from hospital on day 82
• Last clinical review: wound completely healed, incisional
hernia
• HCV RNA negative
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
Acknowledgments
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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)