Tuberculosis in immigrants in Finland, 1995-2013.

Increasing immigration from high tuberculosis (TB) incidence countries is a challenge for surveillance and control in Finland. Here, we describe the epidemiology of TB in immigrants by using national surveillance data. During 1995-2013, 7030 (84·7%) native and 1199 (14·4%) immigrant cases were identified. The proportion of immigrant cases increased from 5·8% in 1995 to 32·1% in 2013, consistent with increasing immigrant population (2·1-5·6%) and decreasing incidence of TB in the native population (from 12·1 to 3·5/100 000). TB cases in immigrants were significantly younger, more often female, and had extrapulmonary TB more often than native cases (P < 0·01 for all comparisons); multidrug resistance was also more common in immigrants than natives (P < 0·01). Immigrant cases were born in 82 different countries; most commonly in Somalia and the former Soviet Union/Russia. During 2008-2013, 433 Mycobacterium tuberculosis isolates from immigrants were submitted for spoligotyping; 10 different clades were identified. Clades were similar to those found in the case's country of birth. Screening immigrants from high-incidence countries and raising awareness of common characteristics and symptoms of TB is important to ensure early diagnosis and to prevent transmission.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

Two cases of food-borne botulism in Finland caused by conserved olives, October 2011.

In October 2011 in Finland, two persons fell ill with symptoms compatible with botulism after having eaten conserved olives stuffed with almonds. One of these two died. Clostridium botulinum type B and its neurotoxin were detected in the implicated olives by PCR and mouse bioassay, respectively. The olives were traced back to an Italian manufacturer and withdrawn from the market. The public and other European countries were informed through media and Europe-wide notifications.

Molecular genetics of drug-resistant Mycobacterium tuberculosis isolates in Finland, 1995-2004.

SETTING: Modern molecular methods help us to understand the transmission and epidemiology of Mycobacterium tuberculosis. OBJECTIVE: To analyse the molecular epidemiology of drug-resistant tuberculosis (TB), and to characterise isoniazid (INH) and rifampicin (RMP) resistance conferring mutations in Finland during 1995-2004. DESIGN: A total of 3959 new M. tuberculosis isolates underwent drug susceptibility testing; all phenotypically resistant isolates were genotyped by IS6110 restriction fragment length polymorphism and spoligotyping if necessary. INH- and/or RMP-resistant isolates were sequenced for their resistance associated genes, katG locus 315 and rpoB, respectively. RESULT: Of the 3959 isolates tested (92.4% of culture-positive cases), 183 (4.6%) were resistant to at least one first-line anti-tuberculosis drug; 14 (0.4%) isolates were multidrug-resistant. Thirty-seven (20.4%) resistant isolates belonged to 17 clusters, and the largest cluster included four isolates. The Beijing family genotype accounted for 8.8% (16 isolates) of all drug-resistant isolates. A Ser315Thr mutation in katG was found in 46.7% (56 isolates) of the INH-resistant isolates and rpoB was mutated in 85.7% (18 isolates) of the isolates resistant to RMP. CONCLUSION: Transmission of drug-resistant TB is rare in Finland, especially between indigenous and immigrant populations. Screening of mutations that confer INH and RMP resistance seems to be feasible if risk factors for multidrug resistance exist.

Healthcare-associated infections in Finnish acute care hospitals: a national prevalence survey, 2005.

The objectives of the first national prevalence survey on healthcare-associated infections (HAIs) in Finland were to assess the extent of HAI, distribution of HAI types, causative organisms, prevalence of predisposing factors and use of antimicrobial agents. The voluntary survey was performed during February-March 2005 in 30 hospitals, including tertiary and secondary care hospitals and 10 (25%) other acute care hospitals in the country. The overall prevalence of HAI was 8.5% (703/8234). Surgical site infection was the most common HAI (29%), followed by urinary tract infection (19%) and primary bloodstream infection or clinical sepsis (17%). HAI prevalence was higher in males, among intensive care and surgical patients, and increased with age and severity of underlying illness. The most common causative organisms, identified in 56% (398/703) of patients with HAIs, were Escherichia coli (13%), Staphylococcus aureus (10%) and Enterococcus faecalis (9%). HAIs caused by multi-resistant microbes were rare (N = 6). A total of 122 patients were treated in contact isolation due to the carriage of multi-resistant microbes. At the time of the survey, 19% of patients had a urinary catheter, 6% central venous line and 1% were ventilated. Antimicrobial treatment was given to 39% of patients. These results can be used for prioritising infection control measures and planning more detailed incidence surveillance of HAI. The survey was a useful tool to increase the awareness of HAI in participating hospitals and to train infection control staff in diagnosing HAIs.

A randomized study on donor immunization with tetanus-diphtheria, Haemophilus influenzae type b and inactivated poliovirus vaccines to improve the recipient responses to the same vaccines after allogeneic bone marrow transplantation.

The HLA-identical sibling donors of 111 bone marrow transplantation (BMT) recipients were randomised to receive or not to receive tetanus-diphtheria (T-d), Haemophilus influenzae type b (Hib), and inactivated poliovirus (IPV) vaccines 2-10 weeks before BM harvest. Fifty-three (DV+ group) recipients received the graft from a vaccinated donor and 58 (DV- group) from an unvaccinated donor. All recipients were vaccinated with the T-d, Hib and IPV vaccines at 3, 6 and 12 months after BMT. Diphtheria and Hib antibody concentrations were consistently higher in the DV+ than in the DV- group from 6 months post transplantation onwards. The differences were significant at 6 and 13 months for diphtheria and at 12 months for Hib antibody concentrations. Tetanus, PV1, PV2 and PV3 antibody levels were similar in both groups. Patients transplanted from donors with high tetanus, diphtheria and Hib antibody concentrations had higher respective antibody concentrations after BMT than those transplanted from donors with low antibody concentrations. Especially patients whose donors have low-specific antibody concentrations may benefit from donor vaccination with protein and conjugate vaccines.

Serious community-acquired neonatal infections in rural Southeast Asia (Bohol Island, Philippines).

OBJECTIVE: To determine the bacterial etiology, clinical presentation and risk factors for outcome of serious community-acquired infections in young infants. STUDY DESIGN: Infants younger than 60 days, admitted for severe pneumonia or suspected sepsis/meningitis were prospectively evaluated using complete blood count, blood culture, chest radiograph, cerebrospinal fluid (CSF) culture in suspected meningitis. chi2 or Fisher's exact test and stepwise logistic regression were used for analysis. RESULTS: Thirty-four of 767 enrolled infants had a positive blood or CSF culture. Gram-negative bacteria were more frequent than Gram positive: overall (P=0.004), in those below 7 days of age (P=0.002) and among home deliveries (P=0.012). Case fatality rates were higher among infants below 1 week old (OR 4.14, P<0.001), those with dense (OR 2.92, P<0.001) or diffuse radiographic infiltrates (OR 2.79, P=0.003). CONCLUSIONS: Gram-negative enteric bacteria are the predominant causes of community-acquired infections in Filipino infants below 2 months old. Age below 7 days and radiographic pneumonia predicted death.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD)--mainly meningitis and septicaemia--and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100,000 in the general population, with a total of 23,470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD) - mainly meningitis and septicaemia - and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100 000 in the general population, with a total of 23 470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculosis, Finland, 1995-2013.

Recurrent tuberculosis (TB) is caused by an endogenous re-activation of the same strain of Mycobacterium tuberculosis (relapse) or exogenous infection with a new strain (re-infection). Recurrence of TB in Finland was analysed in a population-based, 19-year study, and genotyping was used to define relapse and re-infection. The M. tuberculosis isolates from patients with suspected relapse were further analysed by whole genome sequencing (WGS) to determine the number and type of mutations occurring in the bacterial genome between the first and second disease episodes. In addition, publicly available tools (PhyResSE and SpolPred) were used to predict drug resistance and spoligotype profile from the WGS data. Of the 8299 notified TB cases, 48 (0.6%) patients had episodes classified as recurrent. Forty-two patients had more than one culture-confirmed TB episode, and isolates from two episodes in 21 patients were available for genotyping. In 18 patients, the M. tuberculosis isolates obtained from the first and second TB episodes had identical spoligotypes. The WGS analysis of the 36 M. tuberculosis isolates from the 18 suspected relapse patients (average time between isolates 2.8 years) revealed 0 to 38 single nucleotide polymorphisms (median 1, mean 3.78) between the first and second isolate. There seemed to be no direct relation between the number of years between the two isolates, or treatment outcome, and the number of single nucleotide polymorphisms. The results suggest that the mutation rate may depend on multiple host-, strain- and treatment-related factors.

High sensitivity for tuberculosis in a national integrated surveillance system in Finland.

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.

High sensitivity for tuberculosis in a national integrated surveillance system in Finland.

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Nosocomial bloodstream infections in Finnish hospitals during 1999-2000.

Prospective laboratory-based surveillance in 4 Finnish hospitals during 1999-2000 identified 1477 cases of nosocomial bloodstream infection (BSI), with an overall rate of 0.8 BSIs per 1000 patient-days. Of BSI cases, 33% were in patients with a hematological malignancy and 15% were in patients with a solid malignancy; 26% were in patients who had undergone surgery preceding infection. Twenty-six percent of BSIs were related to intensive care, and 61% occurred in patients with a central venous catheter. Sixty-five percent of the 1621 causative organisms were gram positive, 31% were gram negative, and 4% were fungi. The most common pathogens were coagulase-negative staphylococci (31%), Escherichia coli (11%), Staphylococcus aureus (11%), and enterococci (6%). Methicillin resistance was detected in 1% of S. aureus isolates and vancomycin resistance in 1% of enterococci. The 7-day case-fatality ratio was 9% and was highest for infections caused by Candida (21%) and enterococci (18%). The overall rate of nosocomial BSIs was similar to rates in England and the United States, but S. aureus, enterococci, and fungi were less common in our study, and the prevalence of antibiotic resistance was lower.

Effect of transplacentally acquired tetanus antibodies on the antibody responses to Haemophilus influenzae type b-tetanus toxoid conjugate and tetanus toxoid vaccines in Filipino infants.

BACKGROUND: Pregnant women in developing countries are vaccinated with tetanus toxoid (TT) to prevent neonatal tetanus. In populations in which the maternal TT-vaccination program is efficiently implemented, responses of the infant to TT and TT-conjugated vaccines such as Haemophilus influenzae type b (Hib) capsular polysaccaride (PS) TT-conjugate (Hib-TT) vaccine may be depressed. OBJECTIVES: To study the influence of transplacentally acquired anti-TT antibodies on responses to TT vaccination and to Hib-TT vaccine. METHODS: One hundred ninety-four healthy Filipino infants received three doses of a Hib conjugate (either Hib-TT, PRP-OMP or HbOC) with diphtheria-tetanus-pertussis vaccine (DTP) given simultaneously but in a separate syringe at the age of 6, 10 and 14 weeks (primary series). In addition 54 of the study children received a booster dose of Hib-TT at 9 months simultaneously with the measles vaccine. RESULTS: Transplacentally acquired anti-TT did not interfere with the anti-Hib PS antibody (anti-Hib PS) response to any of the conjugates. The transplacentally acquired anti-TT was not significantly associated with the concentration of anti-Hib PS either before or after the booster dose of Hib-TT. High concentrations (> or =1 IU/ml) of transplacentally acquired anti-TT inhibited the infants' anti-TT responses. CONCLUSIONS: High concentration of transplacentally acquired anti-TT did not depress anti-Hib PS responses to the Hib-TT vaccine. On the other hand the high anti-TT concentrations somewhat depressed the anti-TT responses of the infants. However, the anti-TT concentrations attained were in the protective range in all study children after either the primary series (DTP + Hib-TT) or the booster dose of Hib-TT.

Coinfection is common in measles-associated pneumonia.

BACKGROUND: Measles continues to be a significant health problem in developing countries. OBJECTIVES: To describe the clinical features of measles-associated pneumonia (MAP) and to identify other pathogens involved. METHODS: Measles diagnosis was ascertained either by the typical symptom complex or by a sensitive enzyme immunoassay for antibody among children < 5 years of age admitted to the hospital with pneumonia. Other pathogens were identified by blood culture, virus isolation or antigen detection from nasopharyngeal aspirate and antibody determination from serum. RESULTS: Of 182 MAP cases 162 (89%) had clinically typical measles. Twenty patients had a diagnostic antibody finding with an atypical clinical presentation. Thirteen percent were younger than 9 months of age. The case fatality rate was 17%, with a significantly increased odds ratio (OR) for those with cyanosis [OR 4.6, 95% confidence interval (CI) 1.7 to 13], respiratory rate > or = 60/min (OR 3, 95% CI 1.3 to 7) or fulfilling criteria for very severe pneumonia (OR 5.3, 95% CI 2.3 to 12). Mixed infection was found in 53% of patients. Blood culture was positive in 10 patients, Streptococcus pneumoniae (N = 5) being the most common finding. Adenovirus (19%) and parainfluenza (25%) viruses were the most frequent other viruses. A dense infiltrate was seen significantly more often among measles patients with bacterial coinfection (87.5%) than those with other viruses (36%, P = 0.007) or no evidence of other infection (33%, P = 0.004). CONCLUSION: In MAP, coinfection with other microbes is common. Cyanosis and a respiratory rate of > or = 60/min predict a greater risk of dying.

Loss of protective immunity to polio, diphtheria and Haemophilus influenzae type b after allogeneic bone marrow transplantation.

Immunity to poliovirus, diphtheria and Haemophilus influenzae type b (Hib) was studied in 16 adult recipients of a bone marrow transplant from an HLA-identical sibling donor in order to evaluate the need for revaccinations. T-cell depletion was not done in any case. The donors and patients were studied before bone marrow transplantation (BMT) and the patients 1, 3, 6, and 12 months later. Prior to the BMT 10 of 11 patients were immune (titre > or = 4) to all vaccine poliovirus types by a standard microneutralization assay. At 12 months after BMT only two of seven patients were immune to all vaccine types, and none had immunity against an antigenically altered poliovirus type 3 strain Finland. The geometric means of antibody titres against poliovirus types 1, 2, and 3 strain Saukett and strain Finland declined gradually after 1 month postgrafting, being 4.4, 5.4, 3.3, and 1.3 respectively at 12 months after BMT. At 1 year 6 of 11 patients had immunity against diphtheria by a toxin neutralization method, but the antitoxin geometric mean level had decreased to a barely protective level, 0.01 IU/ml. The geometric mean Hib antibody concentration decreased during the first 6 months after BMT and thereafter increased slightly. A significant proportion of BMT recipients lose their protection against polio, diphtheria and Hib, and revaccinations are necessary.

Hepatitis C infection in BMT patients.

Eighty-five patients who had undergone BMT for malignant blood disease or aplastic anemia at the Helsinki University Central Hospital, Finland were tested for hepatitis C antibodies (anti-HCV). Eight (9.4%) patients were anti-HCV positive according to a second generation enzyme linked immunosorbent assay (ELISA). Seven (87.5%) of the ELISA positive results could be confirmed by a supplemental test, the second generation recombinant immunoblot assay (RIBA-4). Two patients were constantly seropositive, one patient was seropositive prior to BMT but became antibody negative soon after BMT, and four patients seroconverted after BMT. Six of the seven confirmed anti-HCV positive patients had biochemical evidence of liver damage, but none had fulminant hepatitis or hepatic failure. Liver enzyme abnormalities consistent with a possible non-A, non-B hepatitis were significantly more prevalent among the seropositive than seronegative patients (p < 0.05). The intensive immunosuppression associated with BMT seemed to have little effect on the ability to produce antibodies for hepatitis C virus (HCV). The pattern of antibodies towards different HCV antigens in RIBA-4 was inconsistent, but the present results suggest that antibodies to a core antigen (C22) may, in some cases, be detected earlier than other HCV antibodies during early HCV infection. Moreover, ELISA became positive earlier than RIBA-4 in some patients.