- Email: [email protected]
Holiday haemodialysis and imported hepatitis C virus infection: A series of sixteen cases in two large haemodialysis units
Journal of Clinical Virology 45 (2009) 296–299
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Holiday haemodialysis and imported hepatitis C virus infection: A series of sixteen cases in two large haemodialysis units Sanjay Bhattacharya a , Nicola Price a , Elizabeth Boxall a , Dwomoa Adu b , Graham Lipkin b , Steve Smith c , Husam Osman a,∗ a b c
HPA West Midlands Laboratory, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, United Kingdom Renal Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom Renal Unit, Heart of England Foundation Trust, Birmingham, United Kingdom
a r t i c l e
i n f o
Article history: Received 5 February 2009 Received in revised form 6 April 2009 Accepted 20 April 2009 Keywords: Hepatitis C infection Holiday haemodialysis Infection control
a b s t r a c t Background: Patients in haemodialysis units are at an increased risk of blood borne virus infections. Birmingham city (West Midlands, UK) has a large number of its population from an ethnic origin other than white (30%). Recently due to the increase in number of haemodialysis centres abroad and particularly in the Indian Subcontinent, a large number of haemodialysis patients from these ethnic minorities are encouraged to take holidays in their countries of origin. Objectives: To present the data on a series of cases of holiday haemodialysis acquired hepatitis C virus (HCV) infections from two large dialysis units in Birmingham. Study design: In this retrospective study we have reviewed the case records of all patients in two large dialysis units who had holiday dialysis abroad and developed HCV infection after returning to the UK. Results: A total of 16 patients from two large dialysis units in Birmingham who developed HCV infection after haemodialysing abroad mainly in the Indian Subcontinent are being described. This constituted 44% of the total HCV positive patients in the two haemodialysis units (16/36). The cases occurred over a period of 9 years between 2000 and 2008. The last twelve of these fifteen cases had been diagnosed in the past 17 months. There were 10 male patients with a mean age 62.8 years (range 26–84 years) and 6 female patients with a mean age of 57 years (range 44–68 years). HCV genotypes 1, 3 and 4 were found in 9, 4 and 3 patients, respectively. Conclusion: These cases underline the importance of enhanced surveillance and infection control procedures in haemodialysis units for patients who return after dialysing in resource poor countries. To the best of our knowledge this represents the largest series of imported HCV infection after holiday haemodialysis, and demonstrates clearly the significance of the perceived risk with increasing number of incident infections. © 2009 Elsevier B.V. All rights reserved.
1. Background Patients on haemodialysis are at increased risk of infections with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis delta virus (HDV) and human T cell lymphotropic viruses (HTLV).1 HCV is the most common blood borne virus (BBV) infection among patients on maintenance haemodialysis with a prevalence of 3% in the UK.1,2 It is likely that patients are at increased risk of acquiring a blood borne virus infection when taking holiday haemodialysis in countries where these viruses have high prevalence and where standards of infection control are inadequate.3–7 About 30% of the Birmingham City’s
∗ Corresponding author. Tel.: +44 0121 424 2513; fax: +44 0121 772 6229. E-mail address: [email protected] (H. Osman). 1386-6532/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2009.04.007
population are from a minority ethnic groups8 (mostly from the Indian Subcontinent as well as Afro-Caribbean), and dialysis units in Birmingham hospitals have a significant number of patients from these groups. In the last few years an increasing number of our haemodialysis patients started taking holidays in their country of origin mainly in the Indian Subcontinent. This has been facilitated by the increase in the number of haemodialysis centres on those countries. However, we also noted the increased number of patients who developed hepatitis C infection after returning from holiday. In our centre all patients returning after having had haemodialysis abroad are dialysed on an isolated machine for 6 months in addition to having enhanced surveillance for blood borne viruses for 3 months. In this article we describe a series of sixteen cases of holiday haemodialysis acquired HCV infection, over a 9-year period to raise awareness of this new phenomenon and to help to illustrate the importance of strict infection control measures.
Positive-genotype 4 Positive-genotype 3a Positive-genotype 1b Positive-genotype 4 Positive-genotype 3a Positive-genotype 1a Positive-genotype 3a Positive-genotype 3a Positive-genotype 1a/1b Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 4
297
2. Objectives
Bil—bilirubin; AST—aspartate aminotransferase; AP—alkaline phosphates; ↑—raised; ↔—normal; HBsAg—hepatitis B surface antigen; HBcAb—HBV core antibody.
Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↑AP↔ Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↑AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↔AP↑ Bil↔AST↑AP↑ Bil↔AST↔ AP↔ Bil↔AST↔ AP↑ Bil↔AST↑AP↑ Bil↔AST↔ AP↑ AP↑ Bil↔AST↑AP↑ 2000/India 2005/Pakistan 2005/India 2006/Saudi Arabia 2007/Pakistan 2007/Pakistan 2007/India 2007/India 2007/Bangladesh 2008/Pakistan 2008/India 2008/Pakistan 2008/Pakistan 2008/Pakistan 2008/Pakistan 2008/India 67 F 71 M 45 F 51 M 51 F 73 M 57 M 67 F 63 M 52 M 84 M 44 F 74 M 26 M 77 M 68 F A—UHB B—UHB C—UHB D—UHB E—UHB F—UHB G—UHB H—HoEFT I—HoEFT J—HoEFT K—HoEFT L—HoEFT M—UHB N—UHB O—UHB P—UHB
Liver function at HCV seroconversion Age (years), sex
Year of diagnosis/likely country of acquisition of HCV
HBsAg-neg, HBcAb-pos, HIV-neg HBsAg-neg, HBcAb-pos, HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-posHIV-neg HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-pos HIV-neg HBsAg-neg, HBcAb-neg HIV-neg HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-not tested, HIV-neg HBsAg-neg, HBcAb-pos HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-neg, HIV-neg
35 days 168 days 178 days 127 days 84 days 181 days 153 days 151 days 73 days 69 days 103 days 78 days 122 days 43 days 91 days 181 days
Fig. 1. Hepatitis C virus in the dialysis unit.
Case/location
Table 1 Clinical and virological profile of 16 patients who became HCV positive after holiday haemodialysis outside the UK.
Other BBV serology
Days between travel and HCV seroconversion
HCV PCR
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
To present the data on a series of cases of holiday haemodialysis acquired hepatitis C virus (HCV) infections from two large dialysis units in Birmingham (UK). 3. Study design In this retrospective study we reviewed the case records of all patients in two large dialysis units who had holiday dialysis abroad and developed HCV infection after returning to the UK. There are 8 haemodialysis units affiliated to and managed by the Renal Unit at University Hospital Birmingham (UHB) with a total number of 745 patients and 5 haemodialysis units under Heart of England Foundation Trust (HoEFT) comprising 359 patients. We identified the imported haemodialysis acquired HCV cases through enhanced laboratory surveillance and retrospective review of case records of all patients who developed BBV infection after haemodialysis abroad. In our centre HCV serology is done as part of regular surveillance, and HCV RNA RT-PCR in case of enhanced surveillance. Before going on holiday the patients undergo a pre-holiday screening for HIV Ag/anti-HIV, HBsAg and anti-HCV antibody. Following return to the UK patients are put on quarantine with separate/dedicated dialysis machines for 6 months. A surveillance programme for blood borne viruses has been in place since the report of Rosenheim Advisory Group.9 The enhanced surveillance protocol as per the department of health guidelines involves doing HBsAg test 2- weekly, HCV RNA RT-PCR twice weekly for 3 months, and testing for HIV based on risk assessment. Patients positive for HCV (antibody with or without RNA) were dialysed as a cohort in a dedicated area. In 2007 ninety patients went on holidays from the dialysis units at Heart of England Foundation Trust (HoEFT) and 17 of them dialysed in high-risk regions (3 in India, 10 in Pakistan, 1 each in Bangladesh, UAE, Saudi Arabia, Morocco). 4. Results A total of 16 patients from two large dialysis units in Birmingham who developed HCV infection after haemodialysing abroad, mainly in the Indian Subcontinent, are being described. Eleven cases occurred at UHB over a period of 9 years (2000–2008) whereas the five cases from HoEFT were detected within a 15 months period during 2007 and 2008 (Table 1). The imported cases constituted 44% of all diagnosed HCV positive patients, during the study period, in both units (11/23 at UHB and 5/13 at HoEFT). All cases of HCV seroconversion in the dialysis units were in patients who had travelled abroad. There were no cases of HCV seroconversion in patients who did not travel abroad (Fig. 1). There were 10 male patients with a mean age 62.8 years (range 26–84 years) and 6 female patients with a mean age of 57 years (range 44–68 years). HCV genotypes 1, 3
298
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
and 4 were found in 9, 4 and 3 patients, respectively. Fifteen of the 16 patients acquired the infection from the Indian Subcontinent (8—Pakistan; 6—India; 1—Bangladesh) and one case acquired the infection in Saudi Arabia. An increasing trend was noted with 1 case only in 2000, 2 cases in 2005, 1 case in 2006, then 5 cases in 2007 and finally 7 cases in 2008 (Fig. 1). Elevation of AST with anicteric hepatitis was observed in the majority of patients at seroconversion (except four patients with normal transaminases). The mean time between the last negative HCV serological test and first HCV positive test was 115 days (range 35–181 days). HCV genotypes were consistent with the common genotypes found in the geographical areas from which the infection was acquired.10–13 All patients tested negative for HBsAg on their return from holiday haemodialysis although 5 of the patients had evidence of past infection with HBV (HBcAb positive). HIV testing was carried out after due consent in twelve patients and they were all negative.
5. Discussion In the UK universal screening of blood and blood products for HCV antibodies was introduced in 1991 and for HCV RNA since 1999.14 The risk of transmission of BBV including HCV through blood or blood product is considered exceedingly rare and is estimated to be about 1 in 30 million.15 Transmission of HCV to patients from contaminated dialysis machines or contaminated blood is another route of infection that can occur due to breaches in the dialysis equipment. However, with modern haemodialysis machines as used in our centre, the chances of machine breaches contributing to BBV transmission are minimal. The HCV seroprevalence in the UHB haemodialysis units is 4.3% (32 HCV seropositive patients out of a total of 745 patients) while that in the HoEFT units is 3.6% (13 HCV seropositive patients out of a total of 359 patients). These figures are similar to the national average of HCV infection (3%) among haemodialysis patients in the UK.1 However, the proportion of individuals with imported HCV due to haemodialysis abroad is disproportionately high (44%; 16 out 36 HCV positive patients in both units). And this trend seems to be on the rise with increasing number of imported infections being reported with each passing year, a phenomenon which is of great concern. Break down of universal infection control practices is the single most important factor responsible for horizontal transmission of HCV in haemodialysis units (patient to patient).16–19 These include poor hand washing practices, not changing gloves and plastic aprons between patients, not wiping down machine and other surfaces with anti-viral solutions between dialyses or the use of multi-dose injection vials. Breaches in infection control practices can also occur from understaffing and lack of training. An inadequate patient to nurse ratio has been previously shown to increase HCV seropositivity and seroconversion rates in haemodialysis units.20,21 Physical proximity to an HCV positive patient and being dialysed in the same session with a HCV positive patient have also been shown to be important risk factors for nosocomial transmission of HCV.22 Therefore it is important to dialyse HCV positive patients in a separate area or ideally in a separate room. Although the UK renal association and the department of health guidelines are explicit regarding the need of surveillance of BBV infections including HCV; there is relatively little discussion regarding epidemiology of haemodialysis related imported HCV infection. Haemodialysis in resource poor settings especially in centres with high background prevalence of BBV and inadequate infection control practices increases the chance of acquisition of BBV including HCV. A recent report from London documents two patients who after haemodialysis in the Indian Subcontinent contracted HCV infection.3 Our report documents sixteen such cases. The increased incidence of holiday haemodialysis acquired HCV infections after
2006 is likely to be resulting from increased frequency of travel by the patients to high-risk areas. This might be because of increased availability of dialysis centres in high-risk areas in the recent years.23,24 The reasons for designating certain countries as high-risk areas are multi-factorial and depends on: (a) prevalence of HCV in the general population; (b) prevalence, incidence and trend of antiHCV in haemodialysis centres; (c) screening for blood borne viruses including HCV in blood and blood products; (d) quality control and quality assurance procedures in laboratories; (e) local experience regarding incidence of infections after haemodialysis abroad. The seroprevalence of HCV in haemodialysis centres in the Asian and Indian Subcontinent has been reported to be high.4,5,6,25,26 Limited health care resource is a major constraint to the safety of haemodialysis in some countries especially in the Indian Subcontinent. Transmission of blood borne viruses can also occur in those countries through contaminated blood because it is not mandatory for laboratories to be accredited or to engage in external quality assurance schemes. For example only a handful of laboratories in India are accredited to the National Accreditation Board.27,28 However, it must be emphasized that transmission of HCV in haemodialysis units is not just restricted to resource poor settings. Several reports of nosocomial transmission of HCV in haemodialysis centres have been reported from Glasgow,15 London,16 France,18 Japan29 and it is important for haemodialysis units in the UK to follow current guidelines and screen all patients upon return from holidays abroad. Nosocomial transmission of HCV in haemodialysis units is avoidable.30 Patients travelling on holidays and planning to have haemodialysis abroad should be made aware of the risks and followed up with appropriate surveillance on their return.30 The possibility of transmission of HCV in haemodialysis units particularly in the Indian Subcontinent remains high because of resource limitations and consequently less than adequate infection control practices. Incident HCV infections within a haemodialysis unit, apart from infection risk, increase the overall cost to the laboratory (through increased testing), to dialysis unit (need for dedicated machine; increased staffing requirements) and to the health sector in general (for monitoring, treatment, management of complications). The current series of cases underline the perils and dilemma associated with medical tourism, and outsourcing of health care. This exotic mode of acquisition of HCV represents a new challenge to infection control and public health. The condition is preventable through better education of patients and relatives, better infection control procedures in the dialysis centres in countries visited, and better quality control and assurance in blood safety and diagnostic testing (HCV). Patients undergoing dialysis has the right to travel, but the personal, public health and economic effects of an individual excursion could be far reaching.
Conflict of interest statement We have had no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. The results presented in this paper have not been published previously in whole or part, except in abstract format.
Acknowledgement The authors would like to acknowledge their gratitude to Karen Tullett, Haemodialysis Access Nurse and Blood Borne Virus nurse at University hospital Birmingham for her contributions in the management of haemodialysis patients with blood borne virus infections.
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
References 1. Department of Health. Potential viral hazards in dialysis units. In: Good practice guidelines for renal dialysis/transplantation units. Prevention and control of blood borne virus infection. London: 2002; 12–18. 2. Jadoul M, Poignet JL, Geddes C, Locatelli F, Medin C, Krajewska M, et al. The changing epidemiology of hepatitis C virus (HCV) infection in haemodialysis: European multicentre study. Nephrol Dial Transplant 2004;19:904–9. 3. Ghafur A, Raza M, Labbett W, et al. Travel-associated acquisition of hepatitis C virus infection in patients receiving haemodialysis. Nephrol Dial Transplant 2007;22:2640–4. 4. Agarwal SK, Dash SC, Irshad M. Hepatitis C virus infection during haemodialysis in India. J Assoc Physicians India 1999;47:1139–43. 5. Chandra M, Khaja MN, Hussain MM, et al. Prevalence of hepatitis B and hepatitis C viral infections in Indian patients with chronic renal failure. Intervirology 2004;47:374–6. 6. Gul A, Iqbal F. Prevalence of hepatitis C in patients on maintenance haemodialysis. Coll Physicians Surg Pak 2003;13:15–8. 7. Huraib S, al-Rashed R, Aldrees A, Aljefry M, Arif M, al-Faleh FA. High prevalence of and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies. Nephrol Dial Transplant 1995;10:470– 4. 8. Census 2001. Key statistics for local authorities. Crown Copyright 2003. 9. Report of Rosenheim Advisory Group Hepatitis and the treatment of chronic renal failure. Department of Health and Social Security, 1972. 10. Mellor J, Holmes EC, Jarvis LM, Yap PL, Simmonds P. Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. J Gen Virol 1995;76:2493–507. 11. Raghuraman S, Shaji RV, Sridharan G, et al. Distribution of the different genotypes of HCV among patients attending a tertiary care hospital in south India. J Clin Virol 2003;26:61–9. 12. Shah HA, Jafri W, Malik I, Prescott L, Simmonds P. Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan. J Gastroenterol Hepatol 1997;12:758–61. 13. Al-Knawy B, Okamoto H, Ahmed El-Mekki A, et al. Distribution of hepatitis C genotype and co-infection rate with hepatitis G in Saudi Arabia. Hepatol Res 2002;24:95. 14. Health Protection Agency. Hepatitis C in England. The Health Protection Agency annual report 2007. London: 2007;18. 15. Soldan K, Barbara JA, Ramsay ME, Hall AJ. Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993–2001. Vox Sang 2003;84:274–86.
299
16. McLaughlin KJ, Cameron SO, Good T, et al. Nosocomial transmission of hepatitis C virus within a British dialysis centre. Nephrol Dial Transplant 1997;12:304–9. 17. Irish DN, Blake C, Christophers J, et al. Identification of hepatitis C virus seroconversion resulting from nosocomial transmission on a haemodialysis unit: implications for infection control and laboratory screening. J Med Virol 1999;59:135–40. 18. de Lamballerie X, Olmer M, Bouchouareb D, Zandotti C, De Micco P. Nosocomial transmission of hepatitis C virus in haemodialysis patients. J Med Virol 1996;49:296–302. 19. Olmer M, Bouchouareb D, Zandotti C, de Micco P, de Lamballerie X. Transmission of the hepatitis C virus in an hemodialysis unit: evidence for nosocomial infection. Clin Nephrol 1997;47:263–70. 20. Saxena AK, Panhotra BR. The impact of nurse understaffing on the transmission of hepatitis C virus in a hospital-based haemodialysis unit. Med Princ Pract 2004;13:129–35. 21. Saxena AK, Panhotra BR, Sundaram DS, et al. Impact of dedicated space, dialysis equipment, and nursing staff on the transmission of hepatitis C virus in a haemodialysis unit of the Middle East. Am J Infect Control 2003;31:26–33. 22. dos Santos JP, Loureiro A, Cendoroglo Neto M, Pereira BJ. Impact of dialysis room and reuse strategies on the incidence of hepatitis C virus infection in haemodialysis units. Nephrol Dial Transplant 1996;11:2017–22. 23. Ali Jaffar Naqvi S. Nephrology services in Pakistan. Nephrol Dial Transplant 2000;15:769–71. 24. Hezel MP, Tuorto S, Adusumilli PS. Dialysis dilemmas. Natl Med J India 2007;20:152. 25. Khokhar N, Alam AY, Naz F, Mahmud SN. Risk factors for hepatitis C virus infection in patients on long-term haemodialysis. J Coll Physicians Surg Pak 2005;15:326–8. 26. Hussein MM, Mooij JM, Roujouleh H, el-Sayed H. Observations in a SaudiArabian dialysis population over a 13-year period. Nephrol Dial Transplant 1994;9:1072–6. 27. National Accreditation Board for Testing and Calibration Laboratories. Directory of accredited medical testing laboratories, New Delhi. Department of Science and Technology, Ministry of Science and Technology, Government of India, 2005. 28. Jesudason MV, Mukundan U, John TJ. External quality assessment scheme in microbiology in India. Indian J Med Microbiol 1995;13:26–9. 29. Hosokawa N, Esumi M, Iwasaki Y, Yanai M, Enomoto A, Kawano K. Phylogenetic evidence, by multiple clone analysis of hypervariable region 1, for the transmission of hepatitis C virus to chronic haemodialysis patients. J Viral Hepat 2000;7:276–82. 30. Improving Global Outcomes. KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of Hepatitis C in chronic kidney disease. Kidney Int 2008; 73 (Suppl. 109): S1–S99.
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Holiday haemodialysis and imported hepatitis C virus infection: A series of sixteen cases in two large haemodialysis units Sanjay Bhattacharya a , Nicola Price a , Elizabeth Boxall a , Dwomoa Adu b , Graham Lipkin b , Steve Smith c , Husam Osman a,∗ a b c
HPA West Midlands Laboratory, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, United Kingdom Renal Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom Renal Unit, Heart of England Foundation Trust, Birmingham, United Kingdom
a r t i c l e
i n f o
Article history: Received 5 February 2009 Received in revised form 6 April 2009 Accepted 20 April 2009 Keywords: Hepatitis C infection Holiday haemodialysis Infection control
a b s t r a c t Background: Patients in haemodialysis units are at an increased risk of blood borne virus infections. Birmingham city (West Midlands, UK) has a large number of its population from an ethnic origin other than white (30%). Recently due to the increase in number of haemodialysis centres abroad and particularly in the Indian Subcontinent, a large number of haemodialysis patients from these ethnic minorities are encouraged to take holidays in their countries of origin. Objectives: To present the data on a series of cases of holiday haemodialysis acquired hepatitis C virus (HCV) infections from two large dialysis units in Birmingham. Study design: In this retrospective study we have reviewed the case records of all patients in two large dialysis units who had holiday dialysis abroad and developed HCV infection after returning to the UK. Results: A total of 16 patients from two large dialysis units in Birmingham who developed HCV infection after haemodialysing abroad mainly in the Indian Subcontinent are being described. This constituted 44% of the total HCV positive patients in the two haemodialysis units (16/36). The cases occurred over a period of 9 years between 2000 and 2008. The last twelve of these fifteen cases had been diagnosed in the past 17 months. There were 10 male patients with a mean age 62.8 years (range 26–84 years) and 6 female patients with a mean age of 57 years (range 44–68 years). HCV genotypes 1, 3 and 4 were found in 9, 4 and 3 patients, respectively. Conclusion: These cases underline the importance of enhanced surveillance and infection control procedures in haemodialysis units for patients who return after dialysing in resource poor countries. To the best of our knowledge this represents the largest series of imported HCV infection after holiday haemodialysis, and demonstrates clearly the significance of the perceived risk with increasing number of incident infections. © 2009 Elsevier B.V. All rights reserved.
1. Background Patients on haemodialysis are at increased risk of infections with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis delta virus (HDV) and human T cell lymphotropic viruses (HTLV).1 HCV is the most common blood borne virus (BBV) infection among patients on maintenance haemodialysis with a prevalence of 3% in the UK.1,2 It is likely that patients are at increased risk of acquiring a blood borne virus infection when taking holiday haemodialysis in countries where these viruses have high prevalence and where standards of infection control are inadequate.3–7 About 30% of the Birmingham City’s
∗ Corresponding author. Tel.: +44 0121 424 2513; fax: +44 0121 772 6229. E-mail address: [email protected] (H. Osman). 1386-6532/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2009.04.007
population are from a minority ethnic groups8 (mostly from the Indian Subcontinent as well as Afro-Caribbean), and dialysis units in Birmingham hospitals have a significant number of patients from these groups. In the last few years an increasing number of our haemodialysis patients started taking holidays in their country of origin mainly in the Indian Subcontinent. This has been facilitated by the increase in the number of haemodialysis centres on those countries. However, we also noted the increased number of patients who developed hepatitis C infection after returning from holiday. In our centre all patients returning after having had haemodialysis abroad are dialysed on an isolated machine for 6 months in addition to having enhanced surveillance for blood borne viruses for 3 months. In this article we describe a series of sixteen cases of holiday haemodialysis acquired HCV infection, over a 9-year period to raise awareness of this new phenomenon and to help to illustrate the importance of strict infection control measures.
Positive-genotype 4 Positive-genotype 3a Positive-genotype 1b Positive-genotype 4 Positive-genotype 3a Positive-genotype 1a Positive-genotype 3a Positive-genotype 3a Positive-genotype 1a/1b Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 1a Positive-genotype 4
297
2. Objectives
Bil—bilirubin; AST—aspartate aminotransferase; AP—alkaline phosphates; ↑—raised; ↔—normal; HBsAg—hepatitis B surface antigen; HBcAb—HBV core antibody.
Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↑AP↔ Bil↔AST↑AP↑ Bil↔AST↑AP↑ Bil↑AST↑AP↑ Bil↔AST↑AP↑ Bil↔AST↔AP↑ Bil↔AST↑AP↑ Bil↔AST↔ AP↔ Bil↔AST↔ AP↑ Bil↔AST↑AP↑ Bil↔AST↔ AP↑ AP↑ Bil↔AST↑AP↑ 2000/India 2005/Pakistan 2005/India 2006/Saudi Arabia 2007/Pakistan 2007/Pakistan 2007/India 2007/India 2007/Bangladesh 2008/Pakistan 2008/India 2008/Pakistan 2008/Pakistan 2008/Pakistan 2008/Pakistan 2008/India 67 F 71 M 45 F 51 M 51 F 73 M 57 M 67 F 63 M 52 M 84 M 44 F 74 M 26 M 77 M 68 F A—UHB B—UHB C—UHB D—UHB E—UHB F—UHB G—UHB H—HoEFT I—HoEFT J—HoEFT K—HoEFT L—HoEFT M—UHB N—UHB O—UHB P—UHB
Liver function at HCV seroconversion Age (years), sex
Year of diagnosis/likely country of acquisition of HCV
HBsAg-neg, HBcAb-pos, HIV-neg HBsAg-neg, HBcAb-pos, HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-posHIV-neg HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-pos HIV-neg HBsAg-neg, HBcAb-neg HIV-neg HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-not tested, HIV-neg HBsAg-neg, HBcAb-pos HIV-neg HBsAg-neg, HBcAb-neg, HIV-not tested HBsAg-neg, HBcAb-neg, HIV-neg HBsAg-neg, HBcAb-neg, HIV-neg
35 days 168 days 178 days 127 days 84 days 181 days 153 days 151 days 73 days 69 days 103 days 78 days 122 days 43 days 91 days 181 days
Fig. 1. Hepatitis C virus in the dialysis unit.
Case/location
Table 1 Clinical and virological profile of 16 patients who became HCV positive after holiday haemodialysis outside the UK.
Other BBV serology
Days between travel and HCV seroconversion
HCV PCR
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
To present the data on a series of cases of holiday haemodialysis acquired hepatitis C virus (HCV) infections from two large dialysis units in Birmingham (UK). 3. Study design In this retrospective study we reviewed the case records of all patients in two large dialysis units who had holiday dialysis abroad and developed HCV infection after returning to the UK. There are 8 haemodialysis units affiliated to and managed by the Renal Unit at University Hospital Birmingham (UHB) with a total number of 745 patients and 5 haemodialysis units under Heart of England Foundation Trust (HoEFT) comprising 359 patients. We identified the imported haemodialysis acquired HCV cases through enhanced laboratory surveillance and retrospective review of case records of all patients who developed BBV infection after haemodialysis abroad. In our centre HCV serology is done as part of regular surveillance, and HCV RNA RT-PCR in case of enhanced surveillance. Before going on holiday the patients undergo a pre-holiday screening for HIV Ag/anti-HIV, HBsAg and anti-HCV antibody. Following return to the UK patients are put on quarantine with separate/dedicated dialysis machines for 6 months. A surveillance programme for blood borne viruses has been in place since the report of Rosenheim Advisory Group.9 The enhanced surveillance protocol as per the department of health guidelines involves doing HBsAg test 2- weekly, HCV RNA RT-PCR twice weekly for 3 months, and testing for HIV based on risk assessment. Patients positive for HCV (antibody with or without RNA) were dialysed as a cohort in a dedicated area. In 2007 ninety patients went on holidays from the dialysis units at Heart of England Foundation Trust (HoEFT) and 17 of them dialysed in high-risk regions (3 in India, 10 in Pakistan, 1 each in Bangladesh, UAE, Saudi Arabia, Morocco). 4. Results A total of 16 patients from two large dialysis units in Birmingham who developed HCV infection after haemodialysing abroad, mainly in the Indian Subcontinent, are being described. Eleven cases occurred at UHB over a period of 9 years (2000–2008) whereas the five cases from HoEFT were detected within a 15 months period during 2007 and 2008 (Table 1). The imported cases constituted 44% of all diagnosed HCV positive patients, during the study period, in both units (11/23 at UHB and 5/13 at HoEFT). All cases of HCV seroconversion in the dialysis units were in patients who had travelled abroad. There were no cases of HCV seroconversion in patients who did not travel abroad (Fig. 1). There were 10 male patients with a mean age 62.8 years (range 26–84 years) and 6 female patients with a mean age of 57 years (range 44–68 years). HCV genotypes 1, 3
298
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
and 4 were found in 9, 4 and 3 patients, respectively. Fifteen of the 16 patients acquired the infection from the Indian Subcontinent (8—Pakistan; 6—India; 1—Bangladesh) and one case acquired the infection in Saudi Arabia. An increasing trend was noted with 1 case only in 2000, 2 cases in 2005, 1 case in 2006, then 5 cases in 2007 and finally 7 cases in 2008 (Fig. 1). Elevation of AST with anicteric hepatitis was observed in the majority of patients at seroconversion (except four patients with normal transaminases). The mean time between the last negative HCV serological test and first HCV positive test was 115 days (range 35–181 days). HCV genotypes were consistent with the common genotypes found in the geographical areas from which the infection was acquired.10–13 All patients tested negative for HBsAg on their return from holiday haemodialysis although 5 of the patients had evidence of past infection with HBV (HBcAb positive). HIV testing was carried out after due consent in twelve patients and they were all negative.
5. Discussion In the UK universal screening of blood and blood products for HCV antibodies was introduced in 1991 and for HCV RNA since 1999.14 The risk of transmission of BBV including HCV through blood or blood product is considered exceedingly rare and is estimated to be about 1 in 30 million.15 Transmission of HCV to patients from contaminated dialysis machines or contaminated blood is another route of infection that can occur due to breaches in the dialysis equipment. However, with modern haemodialysis machines as used in our centre, the chances of machine breaches contributing to BBV transmission are minimal. The HCV seroprevalence in the UHB haemodialysis units is 4.3% (32 HCV seropositive patients out of a total of 745 patients) while that in the HoEFT units is 3.6% (13 HCV seropositive patients out of a total of 359 patients). These figures are similar to the national average of HCV infection (3%) among haemodialysis patients in the UK.1 However, the proportion of individuals with imported HCV due to haemodialysis abroad is disproportionately high (44%; 16 out 36 HCV positive patients in both units). And this trend seems to be on the rise with increasing number of imported infections being reported with each passing year, a phenomenon which is of great concern. Break down of universal infection control practices is the single most important factor responsible for horizontal transmission of HCV in haemodialysis units (patient to patient).16–19 These include poor hand washing practices, not changing gloves and plastic aprons between patients, not wiping down machine and other surfaces with anti-viral solutions between dialyses or the use of multi-dose injection vials. Breaches in infection control practices can also occur from understaffing and lack of training. An inadequate patient to nurse ratio has been previously shown to increase HCV seropositivity and seroconversion rates in haemodialysis units.20,21 Physical proximity to an HCV positive patient and being dialysed in the same session with a HCV positive patient have also been shown to be important risk factors for nosocomial transmission of HCV.22 Therefore it is important to dialyse HCV positive patients in a separate area or ideally in a separate room. Although the UK renal association and the department of health guidelines are explicit regarding the need of surveillance of BBV infections including HCV; there is relatively little discussion regarding epidemiology of haemodialysis related imported HCV infection. Haemodialysis in resource poor settings especially in centres with high background prevalence of BBV and inadequate infection control practices increases the chance of acquisition of BBV including HCV. A recent report from London documents two patients who after haemodialysis in the Indian Subcontinent contracted HCV infection.3 Our report documents sixteen such cases. The increased incidence of holiday haemodialysis acquired HCV infections after
2006 is likely to be resulting from increased frequency of travel by the patients to high-risk areas. This might be because of increased availability of dialysis centres in high-risk areas in the recent years.23,24 The reasons for designating certain countries as high-risk areas are multi-factorial and depends on: (a) prevalence of HCV in the general population; (b) prevalence, incidence and trend of antiHCV in haemodialysis centres; (c) screening for blood borne viruses including HCV in blood and blood products; (d) quality control and quality assurance procedures in laboratories; (e) local experience regarding incidence of infections after haemodialysis abroad. The seroprevalence of HCV in haemodialysis centres in the Asian and Indian Subcontinent has been reported to be high.4,5,6,25,26 Limited health care resource is a major constraint to the safety of haemodialysis in some countries especially in the Indian Subcontinent. Transmission of blood borne viruses can also occur in those countries through contaminated blood because it is not mandatory for laboratories to be accredited or to engage in external quality assurance schemes. For example only a handful of laboratories in India are accredited to the National Accreditation Board.27,28 However, it must be emphasized that transmission of HCV in haemodialysis units is not just restricted to resource poor settings. Several reports of nosocomial transmission of HCV in haemodialysis centres have been reported from Glasgow,15 London,16 France,18 Japan29 and it is important for haemodialysis units in the UK to follow current guidelines and screen all patients upon return from holidays abroad. Nosocomial transmission of HCV in haemodialysis units is avoidable.30 Patients travelling on holidays and planning to have haemodialysis abroad should be made aware of the risks and followed up with appropriate surveillance on their return.30 The possibility of transmission of HCV in haemodialysis units particularly in the Indian Subcontinent remains high because of resource limitations and consequently less than adequate infection control practices. Incident HCV infections within a haemodialysis unit, apart from infection risk, increase the overall cost to the laboratory (through increased testing), to dialysis unit (need for dedicated machine; increased staffing requirements) and to the health sector in general (for monitoring, treatment, management of complications). The current series of cases underline the perils and dilemma associated with medical tourism, and outsourcing of health care. This exotic mode of acquisition of HCV represents a new challenge to infection control and public health. The condition is preventable through better education of patients and relatives, better infection control procedures in the dialysis centres in countries visited, and better quality control and assurance in blood safety and diagnostic testing (HCV). Patients undergoing dialysis has the right to travel, but the personal, public health and economic effects of an individual excursion could be far reaching.
Conflict of interest statement We have had no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. The results presented in this paper have not been published previously in whole or part, except in abstract format.
Acknowledgement The authors would like to acknowledge their gratitude to Karen Tullett, Haemodialysis Access Nurse and Blood Borne Virus nurse at University hospital Birmingham for her contributions in the management of haemodialysis patients with blood borne virus infections.
S. Bhattacharya et al. / Journal of Clinical Virology 45 (2009) 296–299
References 1. Department of Health. Potential viral hazards in dialysis units. In: Good practice guidelines for renal dialysis/transplantation units. Prevention and control of blood borne virus infection. London: 2002; 12–18. 2. Jadoul M, Poignet JL, Geddes C, Locatelli F, Medin C, Krajewska M, et al. The changing epidemiology of hepatitis C virus (HCV) infection in haemodialysis: European multicentre study. Nephrol Dial Transplant 2004;19:904–9. 3. Ghafur A, Raza M, Labbett W, et al. Travel-associated acquisition of hepatitis C virus infection in patients receiving haemodialysis. Nephrol Dial Transplant 2007;22:2640–4. 4. Agarwal SK, Dash SC, Irshad M. Hepatitis C virus infection during haemodialysis in India. J Assoc Physicians India 1999;47:1139–43. 5. Chandra M, Khaja MN, Hussain MM, et al. Prevalence of hepatitis B and hepatitis C viral infections in Indian patients with chronic renal failure. Intervirology 2004;47:374–6. 6. Gul A, Iqbal F. Prevalence of hepatitis C in patients on maintenance haemodialysis. Coll Physicians Surg Pak 2003;13:15–8. 7. Huraib S, al-Rashed R, Aldrees A, Aljefry M, Arif M, al-Faleh FA. High prevalence of and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies. Nephrol Dial Transplant 1995;10:470– 4. 8. Census 2001. Key statistics for local authorities. Crown Copyright 2003. 9. Report of Rosenheim Advisory Group Hepatitis and the treatment of chronic renal failure. Department of Health and Social Security, 1972. 10. Mellor J, Holmes EC, Jarvis LM, Yap PL, Simmonds P. Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. J Gen Virol 1995;76:2493–507. 11. Raghuraman S, Shaji RV, Sridharan G, et al. Distribution of the different genotypes of HCV among patients attending a tertiary care hospital in south India. J Clin Virol 2003;26:61–9. 12. Shah HA, Jafri W, Malik I, Prescott L, Simmonds P. Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan. J Gastroenterol Hepatol 1997;12:758–61. 13. Al-Knawy B, Okamoto H, Ahmed El-Mekki A, et al. Distribution of hepatitis C genotype and co-infection rate with hepatitis G in Saudi Arabia. Hepatol Res 2002;24:95. 14. Health Protection Agency. Hepatitis C in England. The Health Protection Agency annual report 2007. London: 2007;18. 15. Soldan K, Barbara JA, Ramsay ME, Hall AJ. Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993–2001. Vox Sang 2003;84:274–86.
299
16. McLaughlin KJ, Cameron SO, Good T, et al. Nosocomial transmission of hepatitis C virus within a British dialysis centre. Nephrol Dial Transplant 1997;12:304–9. 17. Irish DN, Blake C, Christophers J, et al. Identification of hepatitis C virus seroconversion resulting from nosocomial transmission on a haemodialysis unit: implications for infection control and laboratory screening. J Med Virol 1999;59:135–40. 18. de Lamballerie X, Olmer M, Bouchouareb D, Zandotti C, De Micco P. Nosocomial transmission of hepatitis C virus in haemodialysis patients. J Med Virol 1996;49:296–302. 19. Olmer M, Bouchouareb D, Zandotti C, de Micco P, de Lamballerie X. Transmission of the hepatitis C virus in an hemodialysis unit: evidence for nosocomial infection. Clin Nephrol 1997;47:263–70. 20. Saxena AK, Panhotra BR. The impact of nurse understaffing on the transmission of hepatitis C virus in a hospital-based haemodialysis unit. Med Princ Pract 2004;13:129–35. 21. Saxena AK, Panhotra BR, Sundaram DS, et al. Impact of dedicated space, dialysis equipment, and nursing staff on the transmission of hepatitis C virus in a haemodialysis unit of the Middle East. Am J Infect Control 2003;31:26–33. 22. dos Santos JP, Loureiro A, Cendoroglo Neto M, Pereira BJ. Impact of dialysis room and reuse strategies on the incidence of hepatitis C virus infection in haemodialysis units. Nephrol Dial Transplant 1996;11:2017–22. 23. Ali Jaffar Naqvi S. Nephrology services in Pakistan. Nephrol Dial Transplant 2000;15:769–71. 24. Hezel MP, Tuorto S, Adusumilli PS. Dialysis dilemmas. Natl Med J India 2007;20:152. 25. Khokhar N, Alam AY, Naz F, Mahmud SN. Risk factors for hepatitis C virus infection in patients on long-term haemodialysis. J Coll Physicians Surg Pak 2005;15:326–8. 26. Hussein MM, Mooij JM, Roujouleh H, el-Sayed H. Observations in a SaudiArabian dialysis population over a 13-year period. Nephrol Dial Transplant 1994;9:1072–6. 27. National Accreditation Board for Testing and Calibration Laboratories. Directory of accredited medical testing laboratories, New Delhi. Department of Science and Technology, Ministry of Science and Technology, Government of India, 2005. 28. Jesudason MV, Mukundan U, John TJ. External quality assessment scheme in microbiology in India. Indian J Med Microbiol 1995;13:26–9. 29. Hosokawa N, Esumi M, Iwasaki Y, Yanai M, Enomoto A, Kawano K. Phylogenetic evidence, by multiple clone analysis of hypervariable region 1, for the transmission of hepatitis C virus to chronic haemodialysis patients. J Viral Hepat 2000;7:276–82. 30. Improving Global Outcomes. KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of Hepatitis C in chronic kidney disease. Kidney Int 2008; 73 (Suppl. 109): S1–S99.