Human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma in the Inuit people of Nunavut.
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Adult↗
Biomedical subjects
Antonio Giulivi
Publications and source records attributed to Antonio Giulivi.
Enhanced surveillance of newly acquired hepatitis C virus infection in Canada, 1998 to 2004.
The purpose of this study was to determine trends in disease incidence and recent patterns of hepatitis C virus (HCV) transmission in Canada, using the Enhanced Hepatitis Strain Surveillance System (EHSSS). Demographic, clinical, and potential risk factor information on newly acquired HCV infection, from 1998 to 2004, was collected using standardized questionnaires. During this time period, the reported incidence of newly acquired HCV infection declined by 36.4% from 3.3 cases per 100,000 in 1998, to 2.1 cases per 100,000 in 2004. The disease incidence peaked at 15 to 39 y of age, confirming injecting drug use as the most frequently reported route of transmission. The proportion of cases attributed to health care-acquired HCV infection decreased over this time period. Although the incidence of newly acquired HCV infection in the EHSSS was found to be declining, hepatitis C remains an important public health threat to Canadians. Prevention efforts for HCV should focus on injection drug use, especially for people aged 15 to 39 y.
Adolescent↗
Genetic prion disease: the EUROCJD experience.
A total of 10-15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12-88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt-Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term "gTSE" is preferable to "familial TSE". Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.
Adult↗
Occult hepatitis B virus infection in a North American community-based population.
BACKGROUND/AIMS: Occult hepatitis B virus (HBV) infection [HBV-DNA detection in hepatitis B surface antigen (HBsAg)-negative individuals] may cause acute and/or chronic liver disease. The objective of this study was to document the prevalence of occult HBV in an isolated, North American Inuit community. METHODS: Four hundred and eighty seven HBsAg negative sera (61% of the community population) were available for HBV-DNA testing by real time PCR. Of these, 80 (Group 1) had serologic evidence of resolved HBV infection and 407 (Group 2) were HBV-seronegative. RESULTS: HBV-DNA was detected in 14/80 (18%) and S-variants in 12/14 (86%) samples from Group 1. In Group 2, HBV-DNA was detected in 33/407 (8.1%) and S-variants in 17/33 (52%). In all cases (Groups 1 and 2) viral loads were low (<10(5) viral copies/ml) and clinical or biochemical features did not distinguish HBV-DNA positive from negative individuals. However, S-variants were more common (P<0.0001) in older age groups. CONCLUSIONS: The results of this study indicate that in this community-based population; (1) the prevalence of occult HBV infection is 18% in those with serologic evidence of previous HBV infection and 8.1% in HBV seronegative individuals, (2) age, gender and liver biochemistry findings do not identify those with occult HBV and (3) S-variants are present in the majority of individuals with occult HBV.
Adolescent↗
Economic burden of hepatitis C in Canada and the potential impact of prevention. Results from a disease model.
This Canadian hepatitis C model estimates economic burden of disease using Markov modeling to predict progression over 11 health states annually from 2001 to 2040. Incidence-based estimates help demonstrate the capability to determine cost-effectiveness of programs to prevent different proportions of incident cases. Benefits of prevention increase linearly with the number of incident cases prevented. The model forecasts annual health care costs for the treatment of HCV-related disease ranging from $103 to $158 million over time. Health care costs attributable to 2001 incidence cohort are forecast at $14.6 million for prevention. The increasing cost of HCV provides a framework for further analysis and implementation of long-term policies aimed at appropriate allocation of resources for health in Canada.
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Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2.
Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma worldwide. The purpose of this study was to determine how the HCV structural proteins affect the dynamic structural and functional properties of hepatocytes and measure the extra-hepatic manifestations induced by these viral proteins. A transgenic mouse model was established by expressing core, E1 and E2 proteins downstream of a CMV promoter. HCV RNA was detected using RT-PCR in transgenic mouse model tissues, such as liver, kidney, spleen and heart. Expression of the transgene was analysed by real-time PCR to quantify viral RNA in different tissues at different ages. Immunofluorescence analysis revealed the expression of core, E1 and E2 proteins predominantly in hepatocytes. Lower levels of protein expression were detected in spleen and kidneys. HCV RNA and viral protein expression increased in the liver with age. Histological analysis of liver cells demonstrated steatosis in transgenic mice older than 3 months, which was more progressed with age. Electron microscopy analysis revealed alterations in nuclei, mitochondria and endoplasmic reticulum. HCV structural proteins induce a severe hepatopathy in the transgenic mouse model. These mice became more prone to liver and lymphoid tumour development and hepatocellular carcinoma. In this model, the extra-hepatic effects of HCV, which included swelling of renal tubular cells, were mild. It is likely that the HCV structural proteins mediate some of the histological alterations in hepatocytes by interfering with lipid transport and liver metabolism.
Age Factors↗
Epidemiological study of Creutzfeldt-Jakob disease death certificates in Canada, 1979-2001.
INTRODUCTION: A descriptive epidemiological analysis to update trends of Creutzfeldt-Jakob disease (CJD) deaths, from 1979-2001, was undertaken. METHODS: Cases with CJD as underlying cause were extracted. Age-adjusted death rates by age, sex, and province were calculated. Information on birthplace, autopsy indications and type of work were examined for death certificates from 1979 to 1997. RESULTS: 462 cases were identified between 1979 and 1997. The average annual age-standardized mortality rate was 0.93 deaths per million persons during this period and 1.03 for 1998-2001. Persons 60 years or older demonstrated the highest average annual mortality rate. Rates were slightly higher among males and increased with age. Persons born in Canada accounted for 72% of deaths. Cause of death was verified by autopsy for 9.1% of patients while 21% of deaths indicated that additional information relating to underlying cause was expected. The service industry occupation represented the largest mortality (Quebec does not capture these data). CONCLUSIONS: Canadian rates are consistent with those of the United States and slightly higher than those of certain European countries. Approximately 44% of CJD cases had an autopsy record, though many were incomplete. We are unable to determine a relation with occupation. We recommend annual analysis of CJD death registrations for updated surveillance of trends, as mortality data are an efficient tool for monitoring incidence.
Adolescent↗
Occult hepatitis B virus infection in a North American adult hemodialysis patient population.
Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one adult hemodialysis patients were screened for occult HBV. HBV DNA testing was performed by real-time polymerase chain reaction (PCR) with 2 independent primer sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg positive. Of the remaining 239 HBsAg-negative patients, 9 (3.8%) were HBV DNA positive. Viral loads in these individuals were low (10(2)-10(4) viral copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive. Demographic, biochemical, and HBV serological testing did not help to identify those with occult HBV. In conclusion, the prevalence of occult HBV in adult hemodialysis patients in this North American urban center is approximately 4 to 5 times higher than standard HBsAg testing would suggest. The majority of these infections are associated with low viral loads and a high prevalence of the sG145R mutant. Finally, the demographic, biochemical, and/or serological features of HBV DNA-positive subjects do not distinguish these individuals from the remainder of the dialysis patient population.
Adult↗
Genomic analysis of a recently identified virus (SEN virus) and genotypes D and H by polymerase chain reaction.
BACKGROUND/AIMS: SEN virus (SENV) was discovered in 1999 as a DNA virus with hepatotropic properties. Nine genotypes (A-I) have been identified with genotypes D and H being more prevalent in cases of chronic hepatitis. Attempts to determine whether SENV causes liver disease have been hampered by limited diagnostic testing. METHODS: In the present study, we developed two PCR based assays; a general SENV screening and genotype-specific assay. RESULTS: By screening PCR, the specificity for all SENV genotypes and SENV-related sequences was 20/20 (100%) with confirmation of the results being provided by genomic sequencing. With the genotype-specific PCR, specificities for SENV-D and SENV-H were 7/7 (100%) and 7/11 (64%), respectively. All screening PCR products were cloned and sequenced. The results of sequencing showed high genetic diversity in representative SENV genotypes. Five of twenty patients (25%) had mixed infections with several SENV genotypes. CONCLUSIONS: The screening PCR was useful for identifying cases of SENV infection. However, because of high genetic divergence and mixed co-infection, it was difficult to establish a specific method for genotype distinction. Hence, sequencing is still required for further investigations of SENV as a potential cause of liver disease.
Amino Acid Sequence↗
Comparison of DNA amplification, mRNA amplification, and DNA hybridization techniques for detection of cytomegalovirus in bone marrow transplant recipients.
A total of 676 specimens from 63 recipients of bone marrow allografts were tested for cytomegalovirus (CMV) by the following assays: CMV pp67 NucliSens (NS), AMPLICOR CMV MONITOR (RA), and the Digene CMV DNA test (DG). In a consensus analysis, the sensitivities and specificities were 60 and 99% (NS), 96 and 98% (RA), and 90 and 76% (DG), respectively; for detection of symptomatic CMV infection, they were 60 and 97% (NS), 65 and 97% (RA), and 95 and 77% (DG), respectively. In multivariate analysis, the major risk factor for symptomatic CMV infection was an increase in the viral load in the DG assay; in univariate analyses, maximum viral loads in both DG and RA assays and a rising viral load in the RA assay were also significant. The earliest detection of CMV replication was provided by the RA assay (mean, 39 days posttransplantation), followed by the DG assay (mean, 48 days) and the NS assay (mean, 58 days).
Adolescent↗
Insights into SEN virus prevalence, transmission, and treatment in community-based persons and patients with liver disease referred to a liver disease unit.
To document the prevalence and routes of transmission of SEN virus (SEN-V) in community-based individuals and patients referred to a liver disease unit, stored serum samples obtained from 160 Canadian Inuit and 140 patients with liver disease were tested for SEN-V DNA by polymerase chain reaction. In the community-based population, SEN-V was present in 57 (36%) of 160 persons. SEN-V-positive individuals tended to be younger and were more often male. Liver enzyme levels and serologic markers for hepatitis A and B viruses were similar in SEN-V-positive and SEN-V-negative individuals. SEN-V was present in 30 (21%) of the 140 patients with liver disease. Age, sex, risk factors for viral acquisition, prevalence of symptoms, and liver biochemical and histological findings were similar in SEN-V-positive and SEN-V-negative patients. These results indicate that SEN-V infection is a common viral infection in both healthy individuals and patients with chronic liver disease, that transmission likely occurs via nonparenteral routes, and that SEN-V infection is not associated with higher rates of or more-severe liver disease in persons with preexisting liver disease.
Adult↗
More should be done to protect surgical patients from intraoperative hepatitis B infection.
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General Surgery↗
Effectiveness of leucoreduction for removal of infectivity of transmissible spongiform encephalopathies from blood.
In 1999, the UK implemented universal leucoreduction as a precaution against transmission of variant Creutzfeldt-Jakob disease by transfusion of domestic blood or red blood cells. We aimed to assess how effectively leucoreduction reduced infectivity of transmissible spongiform encephalopathies (TSEs) in blood. 450 mL of whole blood collected and pooled from scrapie-infected hamsters was leucoreduced with a commercial filter. Blood cell concentrations were quantified, and infectivity titres measured. Blood cell recovery and white blood cell removal complied with American Association of Blood Banks standards. Leucofiltration removed 42% (SD 12) of the total TSE infectivity in endogenously infected blood. Leucoreduction is necessary for the removal of white-cell-associated TSE infectivity from blood; however, it is not, by itself, sufficient to remove all blood-borne TSE infectivity.
Animals↗
Hepatitis A, B, and C in Canada. Results from the National Sentinel Health Unit Surveillance System, 1993-1995.
OBJECTIVES: To estimate the incidence of and to describe the risk factors that were associated with the acquisition of hepatitis A, B, and C in well-defined Canadian populations from the Sentinel Health Unit Surveillance System (SHUSS). METHODS: We used the 1993 to 1995 data on hepatitis A, B, and C infection in Canada, collected by SHUSS, a national surveillance system established by the Laboratory Centre for Disease Control in Health Canada in 1993, through consultation and collaboration with provincial partners. We calculated the rates of, and described and discussed the risk factors that were associated with, hepatitis A, B, and C infection, based on the SHUSS surveillance data. RESULTS: From 1993 to 1995, SHUSS reported 92 cases of hepatitis A, 89 hepatitis B, and 720 hepatitis C, yielding a rate of 3.9, 3.8, and 30.3 per 100,000, respectively. The reported rates varied substantially among participating health units, ranging from 0.8 to 8.1 per 100,000 for hepatitis A, 0.0 to 9.0 for hepatitis B, and 5.4 to 73.3 for hepatitis C. The most frequently reported risk factor for hepatitis A was a history of street drug use, followed by recent international travel and household contact with a hepatitis A case, household crowding, and a history of raw or undercooked shellfish consumption. The most frequently reported risk factors for the acquisition of hepatitis B included history of street drug use and occupational exposure. The most frequently reported risk factor for the acquisition of hepatitis C was a history of street drug use, followed by health care exposure and occupational exposure. Only 5% of persons with hepatitis B infection had a history of hepatitis B immunization. INTERPRETATION: Despite the limitations of possible bias due to selective participation of SHUSS and the lack of information on risk factors among controls, the high exposure to known risk factors and the low rate of vaccination among hepatitis patients can provide useful information for the development of public health policies to control hepatitis A, B, and C infection in Canada.
Canada↗
Development of a computer linkage system for a blood recipient notification program in Nova Scotia.
OBJECTIVES: To assess the potential uses of computer-assisted record linkage in the surveillance of infectious diseases, using the Nova Scotia blood recipient notification program as the example. METHODS: We developed a computer-assisted, multiple-pass, probabilistic record linkage to link records for blood recipients identified by the Nova Scotia notification program (Nova Scotia Phase I Blood Bank File information) with corresponding Nova Scotia Health Card Registration File records to obtain current mailing addresses to contact potentially living recipients. We used variables available from both files (e.g., name, date of birth, gender, and health care registration number) to link records, after eliminating duplicates/deceased cases. RESULTS: Among 23,925 eligible records in the Nova Scotia Phase I Blood Bank File (1984-1990), there were 1,818 (7.8%) duplications and 8,675 deceased cases, leaving 13,432 cases for linkage. 8,713 (65%) cases were successfully linked to the 1998 Health Card Registration Data File for current mailing addresses. INTERPRETATION: Multiple-pass linkage seems acceptable for maximizing detection of correctly matched records for look-back projects. To overcome quality/lack of information obstacles, future look-back linkages should explore the use of supplementary data files (tax files, voter lists, license files, other provincial databases) to obtain most current addresses.
Disease Notification↗
An epidemiologic study of hepatocellular carcinoma in Canada.
BACKGROUND AND METHODS: To provide information on poorly described Canadian hepatocellular cancer epidemiology, we analyzed incident cases abstracted from the Canadian Cancer Registration Database (1969-1997) and Canadian annual death data (1969-1998). Age, sex, geographic distribution, and secular trends were described. Projection models were developed for the next decade. RESULTS: Results indicated much higher incidence and mortality rates in males than females, with substantial increases for both with age. Age-standardized incidence rates increased an average of 3.4% per year in males, 1.2% per year in females (1969-1997). Age-standardized mortality rates increased an average of 1.48% in males, but decreased an average of 0.46% per year in females (1969-1998). Join-point analysis of the linear trends in the age-standardized incidence and mortality rates suggested that a new trend started to emerge about 1991. The fitted non-linear multiplicative model predicted the occurrence of 1,565 new cases and 802 deaths in the year 2010. HCC incidence was the highest in British Colombia, followed by Quebec, and the lowest in the Atlantic region. CONCLUSIONS: Incidence rates of hepatocellular carcinoma have increased substantially, consistent with the reported increase in the prevalence of Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) infections in recent decades.
Canada↗
Physician survey on knowledge and reporting practices of transfusion-transmitted infections in Canada.
OBJECTIVE: To assess physicians' knowledge and reporting practices of transfusion-transmitted infections (TTI). DESIGN: Cross-sectional postal survey. TARGET POPULATION: Family physicians and specialists. METHODS: A survey questionnaire was sent by mail to 1,359 randomly selected physicians across Canada, and was followed up by a reminder telephone call. RESULTS: A total of 546 (40%) physicians completed and returned the questionnaire. The data from 512 eligible practitioners across Canada were analyzed. Almost all physicians were knowledgeable on the transmission of HIV, HBV and HCV through blood and plasma derivatives. However, physicians' knowledge, particularly the family physicians', was generally lower for less well-known TTIs. For example, only 7.2% of family physicians recognized Babesiosis as a TTI. Of the total 318 physicians who have encountered patients with possible TTI, 50% of them reported such cases to public health or other authorities and many reported to more than one organization. Of the total 159 non-reporting physicians, 91.1% explained that the cases were already reported by laboratories or other physicians. More than 90% of respondents think that it is important or very important that physicians report the cases of TTI to public health authorities for the purpose of surveillance, and more than 80% of them think that it is important or very important to include TTI as a separate entity in the communicable diseases surveillance systems. CONCLUSION: The majority of physicians recognize the more common TTIs and only 50% of them reported such cases. The majority of physicians support the reporting of TTI to public health authorities for surveillance. Recommendations are made to increase physicians' knowledge and reporting of TTI.
Canada↗