| | Impact of dedicated space, dialysis equipment, and nursing staff on the transmission of hepatitis c virus in a hemodialysis unit of the middle east☆Abstract Background: Infection with the hepatitis C virus (HCV) is endemic in hemodialysis (HD) units, especially in Middle Eastern countries. The meticulous isolation policy recommended for patients with the hepatitis B virus (HBV) in an HD unit resulted in a significant drop in HBV incidence globally. This study was developed to prospectively investigate the impact of an identical isolation policy on incidence of nosocomial HCV infection in this HD unit of the Middle East. Methods: In phase I of the study, we retrospectively reviewed the records of 189 patients with a mean age of 47.5 ± 11.4 years (range, 15-85 years) who were receiving maintenance HD from December 7, 1995, to December 6, 2000, for the mean duration of 73 ± 6.3 months (range, 3-144 months) to record the prevalence of HCV. Factors such as blood transfusions and dialytic age (time span that patient has received dialysis since its initiation) implicated in transmission of HCV in the HD unit also were recorded. Phase II involved stringent isolation of anti-HCV positive patients detected during phase I through provision of dedicated space, dialysis equipment, and nursing staff from December 7, 2000, to December 6, 2001. Liver function and anti-HCV tests were repeated for all the 198 patients every 6 months to identify new HCV seroconversions. Results: An HCV prevalence rate of 43.9% (83/189) and an annual HCV seroconversion rate of 6.8% were identified in this cohort. No significant association with blood tranfusion was observed. Eighty-three anti-HCV positive (43.9%) patients had a mean dialytic age of 48.5 ± 14.2 months compared with 25.0 ± 8.6 months among 106 (56.1%) anti-HCV negative patients (relative risk [RR], 1.89; 95% confidence interval [CI], 1.39-5.86; P < .001). Only 2 new HCV seroconversions (1.01% [2/198]) were identified. Conclusions: Evidently, the sharing of facilities in a high-risk HD environment for a prolonged dialytic age facilitates the nosocomial transmission of HCV infection. A significant decline of annual seroconversion rate from 6.8% to 1.01% (odds ratio [OR], 7.535; 95% CI, 1.598-48.89; P < .005) suggests that a comprehensive, strictly enforced isolation policy for HCV-positive patients may play a significant role in limiting HCV transmission in HD units, just as it has in drastically reducing HBV transmission in these settings. (Am J Infect Control 2003;31:26-33.)
More than 100 million people worldwide and approximately 4 million people in the United States are chronically infected with the hepatitis C virus (HCV).1 The prevalence of HCV infection in patients undergoing dialysis is persistently greater than that in the general population. It is endemic in hemodialysis (HD) units around the world, predominantly in Mediterranean and developing countries of the Middle East and Far East (Table 1).2, 3, 4, 5, 6, 7, 8, 9, 10, 11
Several risk factors for HCV transmission in patients undergoing HD have been recognized, including multiple blood transfusions, dialytic age, dialyzer reuse, and the environment of HD units. Nosocomial transmission of HCV has been reported to be the major route of HCV infection in modern hospital dialysis units.11, 12, 13, 14, 15 Thus, HD creates a high-risk environment for the spread of viral infections, including the hepatitis B virus (HBV). Even though the incidence of new cases of HBV has significantly declined in HD units because of stringent isolation of patients, routine screening of blood products, and beneficial effects of prophylactic vaccination, the incidence of HCV infection is still rising at an alarming pace among patients undergoing HD despite adherence to the universal infection control precautions recommended by the Centers for Disease Control and Prevention (CDC). Increased seroconversion rates have been reported from HD units with high prevalence rates, resulting in increased morbidity, mortality, cost of managing end-stage renal disease (ESRD), and human suffering as well as an enormous economic burden on limited health care resources, especially in developing countries.15, 16
As a result, the prevention of HCV transmission in HD units through novel means must be emphasized. The strict implementation of CDC guidelines for isolation of HBV-positive patients might be valuable in limiting the seroconversion rates to HCV in HD units.
Methods  This study attempts to determine the impact of stringent isolation of anti-HCV positive patients undergoing HD and meticulous adherence to universal infection control measures recommended by the CDC, on the transmission of HCV infection at this tertiary care center. Patient isolation included the provision of dedicated dialysis space, hemodialysis equipment, and nursing staff. Phase I of the study consisted of a retrospective review of the records of 189 patients with ESRD who had diverse etiologic findings and were enrolled for HD from December 7, 1995, to December 6, 2000, at King Fahad Hospital and Tertiary Care Center in Hofuf, Saudi Arabia. The mean age of the patients was 47.5 ± 11.4 years (range, 15-85 years). There were 91 (48.2%) men and 98 (51.8%) women in the study. All the patients had ESRD and had been undergoing HD for a mean duration of 73.5 ± 6.3 months (range, 3-144 months). These ESRD patients underwent dialysis 2 or 3 times per week with disposable single-use high-flux dialyzer membranes (polysulphone; Bellco, Mirandola, Italy, and polyacrylonitrile [Filtrat 10 AN 69; Hospal, Meyzieu, France]) and disposable single-use blood lines in a common space devoid of any permanent partition between HCV-positive and HCV-negative patients, except for a washable polyvinyl screen hanging from the ceiling between them. There was no specific assignment of HD staff nurses regarding serologic status of patients to HCV during this phase. The patient-to-nursing staff ratio was 3:1, with the same staff nurses taking care of HCV-positive and HCV-negative patients at the same time. However, male and female patients were dialyzed in separate areas. Infection control precautions Strict adherence to Universal Precautions for infection control as recommended by CDC was practiced routinely for all the patients, irrespective of their serologic status for HCV or HBV, throughout and beyond this study period in our HD center.17 This includes changing gloves after each patient manipulation and frequent handwashings between care of each patient. All the staff members taking care of patients undergoing HD wear gowns, masks, gloves, and protective eyewear while performing procedures and during initiation and termination of dialysis. These protective coverings are changed immediately if they are soiled with blood, body fluids, secretions, or excretions and also before initiation of the next dialysis session. Meticulous cleaning and disinfection of environmental surfaces at each dialysis station before the beginning of the next HD session are routinely performed. Environmental disinfection included cleaning the dialysis equipment, dialysis beds, chairs, tables, and countertops with detergent germicide solutions, with special attention given to the control panels of dialysis machines and other surfaces that are frequently touched and potentially contaminated with a patient's blood. Items taken to the dialysis rooms were either disposable or dedicated for use only on a specific patient (eg, adhesive tapes, cloth-covered blood pressure cuffs, scissors, clamps, stethoscopes). If there was a blood spill, the area was immediately cleaned with cloth soaked in a 1:100 dilution of sodium hypochlorite solution. After all visible blood was cleaned up, a new towel was used to apply disinfectant a second time. All disposable items were placed in a plastic bag thick enough to prevent leakage. Wastes generated in our center were routinely disposed of properly in an incinerator, according to the Saudi regulations governing medical waste disposal. Eating by staff nurses and other dialysis personnel is restricted to the dining room only. However, patients were served snacks and lunch in disposable containers covered with aluminum foil supplied from the hospital kitchen, especially for renal patients. Patients were not allowed to share articles with each other, including food and drinks. Medications were supplied through the pharmacy of the HD unit to each patient only after the dialysis session was completed. Only single-dose vials of human recombinant erythropoietin injections were used. Disinfection of hemodialysis machines The HD machines for HCV-positive patients were used after chemical and hot water disinfection for the HCV-negative patients. A strict protocol of careful chemical disinfection (citrosteril), as per manufacturer instructions, was performed at 85°C for 35 minutes after each dialysis session before the machine was used with the next patient. Hot water, at 80°C to 90°C, was run at a high flow rate after full chemical disinfections for 60 minutes. This procedure was performed at the end of the day on every machine in preparation for the next day's work, and disinfection of the dialysate circuit was performed with sodium hypochlorite after each individual session. External, disposable venous and arterial pressure transducer filters were also changed and discarded between each patient treatment after single use. Isolation of HbsAg-positive patients Patients with HBV infection underwent dialysis separately in isolated rooms in both the male and female areas with dedicated machines, equipment, instruments, supplies, and medications, as per guidelines of CDC (see Fig 1).18 Staff nurses (patient-to-nurse ratio, 2:1) who were caring for HbsAg-positive patients were not allowed to take care of other patients at the same time, including during the period when dialysis was terminated on 1 patient and initiated on another. Disinfections of HD machines (2008 E Fresenius; Schweinfurt, Germany, and Monitral S; Hospal, Medolla, Italy) were performed with hot water as well as chemical disinfectants per manufacturer recommendations before initiation of each dialysis session. Dialyzers and blood lines and other disposable items were discarded after single use. Blood samples were collected from all the HD patients, and serum was stored at −20°C until analyzed for anti-HCV antibodies with second generation enzyme-linked immunosorbent assays (ELISA-2) that use Murex version III kits (Murex Diagnostics, France). All the anti-HCV positive samples were confirmed with immunoblot assay, CHIRON-RIBA-HCV 3.0 (Ortho Clinical Diagnostics, Raritan, NJ). HbsAg ELISA was performed for all these patients with use of Abott Diagnostic kits, Chicago, Ill). Isolation of anti-HCV positive patients Phase II was a prospectively designed study comprising strict isolation of all the HCV-positive patients, which is identical to that recommended by CDC for HbsAg-positive patients, from December 7, 2000, to December 6, 2001. Patient isolation included the provision of designated dialysis space, dedicated hemodialysis machines, and nursing staff, with the patient-to-nurse ratio remaining at 3:1. The strict isolation of HBV-positive patients, heat and chemical disinfection of HD machines, and rigorous implementation of universal infection control precautions adhered to in phase I were continued in phase II. HCV and HBV serologic statuses were repeated for all the 198 ESRD patients after 1 year with identical assays as those in phase I. Five renal physicians, 38 staff nurses, and 2 HD technicians were directly involved in patient care. All personnel are regularly tested (once/year) for anti-HCV/HbsAg and liver enzymes. No HD personnel had positive results for HBV/HCV at any stage during or after the study. Each nurse and HD technician was independently interviewed and regularly observed while at work by a panel that included the chief of infection control and nursing supervisor to assess for adherence to universal safety measures for infection control. Blood and the blood products used for transfusion that had been acquired from voluntary donors were routinely screened for anti-HCV, HbsAg, and HIV. Statistical analysis The quantitative variables are expressed as mean ± standard deviation (SD). The statistical analysis was performed with the Web χ2 Calculator (Georgetown University, Washington, DC). Statistical significance was set at the .05 level.
Results  In phase I, 83 (43.9%) of 189 ESRD patients undergoing HD (mean age, 44.8 ± 10.6 years) were anti-HCV positive, including 35 (42.2%) men and 48 (57.8%) women. The remaining 106 (56.1%) patients (mean age, 49.2 ± 22.3 years) were anti-HCV negative. No significant relationship of anti-HCV positivity with age or sex was observed in the study (P < NS). However, there was a positive correlation between the HCV positivity and the dialytic age (the time span of the administration of hemodialysis since its initiation). The cohort of 83 patients who had positive results for anti-HCV antibodies had a mean dialytic age of 48.5 ± 14.2 months, compared with 25.0 ± 8.6 months among the 106 anti-HCV-negative patients (RR, 1.89; 95% CI, 1.39-5.86; and P < .001). Of the 83 anti-HCV positive patients, 79 (95.2%) had received multiple blood transfusion (9.2 ± 4 units) at some stage during the period they underwent HD, whereas the remaining 4 (4.8%) patients who had positivie results for anti-HCV antibodies had never received blood transfusions since the beginning of their HD treatment. Moreover, of 106 anti-HCV negative patients, 92 had received multiple (mean, 7 ± 2.2) units of blood transfusions. An average seroconversion rate of 6.8% per year for HCV was recorded during phase I of the study (Table 2).
| | |  | HCV serologic findings | No. of patients (%) | Age (y) Mean ± SD | No. of men (%) | No. of women (%) | Dialytic age (mo)* Mean ± SD | Blood transfusion (No. units) Mean ± SD | Seroconversions/y Mean (%) |  |
 | Anti-HCV positive | 83 (43.9) | 44.8 ± 10.6 | 35 (42.2) | 48 (57.8) | 48.5 ± 14.2† | 9.2 ± 4 | 13.5 (6.8) |  |
 | Anti-HCV negative | 106 (56.1) | 49.2 ± 22.3 | 56 (52.8) | 50 (47.2) | 25.0 ± 8.6† | 7 ± 2.2 | |  |
 | Total | 189 | | 91 (48.2) | 98 (51.8) | | | |  |
 | *Dialytic age is the time span of the administration of hemodialysis since its initiation. †Relative risk, 1.89; 95% confidence interval, 1.39-5.86; P < .001. |  | | | |
Only 14 (7.4%) of 189 patients had positive results for HbsAg dialyzed in strict isolation. No new HBV seroconversion was documented during this phase of the study. In phase II, 85 (42.9%) of 198 patients (mean age, 45.2 ± 12.6 years) had anti-HCV positive results, including 37 (43.0%) men and 48 (57.0%) women. The other 113 (57.1%) patients (mean age, 51.3 ± 24.2 years) continued to have a negative status for anti-HCV antibodies. The number of units of blood transfused in anti-HCV positive and anti-HCV negative cohorts was comparable (12.9 ± 3 vs 8.8 ± 5 units), indicative of no significant relationship between an anti-HCV positive rate and units of blood transfusion (Table 3).
| | |  | HCV serologic findings | No. of patients (%) | Age (y) Mean ± SD | No. of men (%) | No. of women (%) | Dialytic age (mo)* Mean % SD | Blood transfusion (No. units) Mean % SD | Seroconversions/y No. (%) |  |
 | Anti-HCV positive | 85 (42.9) | 45.2 ± 12.6 | 37 (43) | 48 (57) | 50.2 ± 14 | 12.9 ± 3 | 2 (1.01) |  |
 | Anti-HCV negative | 113 (57.1) | 51.3 ± 24.2 | 59 (51.8) | 54 (48.2) | 26.3 ± 9.5 | 8.8 ± 5 | |  |
 | Total | 198 | | 96 (48.5) | 102 (51.5) | | | |  |
 | *Dialytic age is the time span of the administration of hemodialysis since its initiation. |  | | | |
Two new anti-HCV positive cases (none of them belonging to the added 9 after phase I) occurred over 12 months of study period, leading to an HCV seroconversion rate of 1.01% per year. However, no new HBV seroconversion was documented during this phase of the study as well.
Discussion  An anti-HCV antibody prevalence rate of 43.9% observed in this study is comparable to the reported HCV prevalence rate of 43.2% in the Eastern Province of the Kingdom of Saudi Arabia.19 However, it is much less than that reported by other HD centers in the kingdom. Higher anti-HCV positivity (72.3%) has been reported in the Western Province of Saudi Arabia.20 In another multicenter study,21 an anti-HCV positivity rate of 68% was reported. Even though, repeated blood transfusions have been reported to be a risk factor for HCV transmission in HD units, data on correlation between anti-HCV positivity and number of blood transfusions are inconclusive.6, 8, 15, 21, 22, 23 Our results do not link the acquisition of HCV in an HD unit with transfusions, as 4 (4.8%) of our patients undergoing HD who received no blood transfusions had positive results for anti-HCV antibodies. The majority of the patients undergoing HD (56.1%) who remained HCV-negative received multiple blood transfusions (mean, 7 ± 2.2 units) during the period they underwent HD. Blood transfusions had been the major source of HCV infection for many years, but with sensitive HCV screening tests for blood donors (ELISA-HCV), the risk of post-transfusion HCV infection has been found to be less than 1/100,000 blood units.24 Moreover, HCV antibody positivity among blood donors in this region is 1.5% (B.R. Panhotra, personal communication), which is significantly less than that of the HD cohort of this center, indicating that overall anti-HCV positivity in the Al-Hasa general population is low. This would seem to indicate an alternative mode of HCV transmission. In our study, as in many others, the time span of dialysis since its initiation (dialytic age) is clearly associated with the risk of development of HCV infection.5, 25 Phase I of this study shows a significant relationship between dialytic age and anti-HCV positivity. Patients with a dialytic age of 48.5 ± 14.2 months had an 89% (RR, 1.89) higher risk of developing HCV infection than those with a dialytic age of 25.0 ± 8.6 months (P < .001). However, an increased dialytic age, per se, conceivably is not a precise risk factor for the development of HCV infection because it merely increases the time span of patients' exposure to a high-risk HD environment to facilitate the HCV nosocomial transmission. Molecular studies of HCV implicate nosocomial transmission of the virus in patients undergoing HD.26 Nosocomial transmission has been reported to be the foremost route of HCV infection in HD units worldwide. Transmission often occurs through blood contamination of gloves and hands of HD staff nurses, dialysis equipment, and dialyzer and blood line surfaces and the use of reprocessed dialyzers.12, 13, 14, 15 A recent clinicovirologic study27 from the Middle East demonstrated the presence of HCV-RNA in the handwashing of nurses administering dialysis to HCV-positive and HCV-negative patients. The sharing of HD machines has been shown to play a role in the transmission of HCV infection,8, 15, 22, 28 whereas the use of separate machines for HCV-positive patients in addition to strict adherence to universal infection control measures led to a decline in the incidence of HCV seroconversion.29 Abu-Aisha et al30 observed that chemical disinfection does not appear to be an adequate safeguard against HCV. The passage of HCV across the dialysis membrane is a controversial issue.31, 32 The passage of HCV is theoretically not possible since the diameter of the virus is much larger than pore size of dialysis membranes. Conversely, disruption of the membrane integrity could hypothetically permit the passage of the virus into the blood compartment in the units where reprocessing of dialyzers is practiced routinely.33 However, Valtuille et al34 recently detected Hepatitis C virus-ribonucleic acid (HCV-RNA) by polymerase chain reaction (PCR) in the ultrafiltrate from HCV-positive patients undergoing HD through single-use dialyzers. The viral contamination of the ultrafiltrate may constitute a potential risk for HCV infection in HD units. In addition, sporadic failures to observe strict measures of asepsis and infection control have led to outbreaks of HCV transmission in HD units.34 Gilli et al35 reported an outbreak of HCV in an HD unit due to the sharing of multidose heparin vials by patients on the same shift. We observed an average annual seroconversion rate of 6.8% at this center, which is comparable to the seroconversion rates of 7% to 9% per year in other HD centers in Saudi Arabia and those reported elsewhere.21, 36 Annual seroconversion rates of more than 5% per year have been reported in HD units with prevalence rates of 20%.15 In phase II of this study, strict isolation of all the anti-HCV positive patients was carried out for 12 months and continued subsequently through the provision of designated dialysis space, and dedicated hemodialysis machines, and the nursing staff. Nevertheless, the similar patient-to-nurse ratio of 3:1 and carefully HCV-screened blood transfusions, and when necessary the optimal use of recombinant human erythropoietin (EPO) that tends to reduce the blood transfusion requirement, were continued to be practiced as in phase I. However, regardless of complete isolation of anti-HCV positive patients and rigorous implementation of meticulous universal control measures, 2 new anti-HCV positive cases occurred over 12 months of the study period, resulting in an HCV seroconversion rate of 1.01% per year in phase II. These 2 newly seroconverted patients were men who underwent dialysis during different shifts and in different rooms. Yet, the seroconversion rate observed in the study was significantly less (6.8% vs 1.01% per year) than that recorded during phase I of this study (OR, 7.535; 95% CI, 1.598-48.89; P < .005.) One of the patients who underwent seroconversion had traveled to a Far East country 6 months before having anti-HCV positive test results to explore the possibility of obtaining a live, unrelated donor transplant. A strong correlation between “holiday dialysis” and anti-HCV seroconversion has been reported in patients who underwent dialysis in units with a high anti-HCV prevalence during their holidays.14, 37 A time interval of 4 to 6 months between the exposure to HCV infection and the appearance of detectable levels of anti-HCV antibodies in the blood has been reported.38 The other patient who tested anti-HCV positive 8 months later never underwent dialysis outside this unit, suggesting that his exposure to HCV infection was within this HD unit, possibly before the implementation of the isolation policy. A number of studies have shown that incidence of HCV infection in patients treated with continuous ambulatory peritoneal dialysis or home hemodialysis is clearly less than that for those treated in hospital-based HD units.39 It is evident that simply sharing the high-risk dialysis environment for 3 to 4 hours for each HD session per week may be sufficient for the spread of HCV through cross-infection. A significant decline in the HCV seroconversion rate was achieved within 12 months of implementation of an isolation policy on the basis of removing anti-HCV positive patients from the cohort of noninfected dialysis patients. It may, therefore, be concluded that a comprehensive, strictly implemented isolation policy of HCV-antibody positive patients can play a significant role in limiting HCV transmission in HD units.
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Nephrol Dial Transplant. 1995;10:240–246. MEDLINE Hofuf, Al-Hasa, Saudi Arabia From the Division of Nephrologya; Post-graduate Department of Microbiologyb; and Department of Infection Control.c ☆ Reprint requests: Anil K. Saxena, MD, MRCP, King Fahad Hospital and Tertiary Care Center, Hofuf, Al-Hasa-31982, Saudi Arabia. PII: S0196-6553(02)48255-7 doi:10.1067/mic.2003.55 © 2003 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. | |
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