Epidemiological, biological and histological characterization of patients with indeterminate third-generation recombinant immunoblot assay antibody results for hepatitis C virus.

We studied the epidemiological, laboratory and histological characteristics of a group of patients with positive antibodies against hepatitis C virus (HCV) as determined by third-generation enzyme-linked immunosorbent assay (ELISA), and with indeterminate HCV antibody positivity as established by third-generation recombinant immunoblot assay (RIBA-3). The results obtained were compared with those recorded in a group of RIBA-3-positive patients. Both groups correspond to blood donors in whom the prevalence of hepatitis C is low. There were no statistically significant intergroup differences in mean age, or in the presence of infection risk factors. RNA positivity was much more frequent in the RIBA-positive group (71%vs 10%; P < 0.05), as was transaminase elevation during the 3 years of follow-up (54%vs 13%; P < 0.05). In 46% of the RIBA-indeterminate patients the liver biopsy proved normal, or only liver steatosis or minimal changes were detected, while 33% had persistent chronic hepatitis, and 21% showed active chronic hepatitis. A mean Knodell index score of 2.28 was recorded; 50% of the subjects showed no fibrosis, 46% grade 1 fibrosis (fibrous portal expansion), 4% grade 2 fibrosis (bridging fibrosis), and none grade 3 fibrosis (liver cirrhosis). In the RIBA-positive group, a greater percentage of patients had active chronic hepatitis, a greater Knodell index, and increased-grade fibrosis. It can be concluded that the RIBA-3-indeterminate group is epidemiologically similar to the RIBA-3-positive series, although with a lesser prevalence of laboratory test alterations, a lower viral replication index, and more likely to have benign disease - particularly in subjects without viral replication.

Long-term response to interferon plus ribavirin in patients with chronic hepatitis C refractory to interferon.

OBJECTIVE: A sustained response (SR) to interferon (IFN) is only observed in 15-20% of patients with chronic hepatitis C (CHC). The aim of this study was to determine the long-term effectiveness and safety of the treatment with IFN plus ribavirin (RIB) over two years in CHC patients without SR to IFN. DESIGN: A prospective and open longitudinal follow-up study was conducted over 3 years. PATIENTS AND METHODS: A total of 77 CHC patients were included: 63 non-responders (NR) and 14 relapsers (R) to IFN. Patients were treated with IFN (3 MU s.c. three times a week) and RIB (1,000-1,200 mg p.o. daily) for 12 months. Treatment tolerance and viral response (HCV-RNA in serum < 1,000 copies/ml) were assessed after 1, 3, 6 and 12 months of treatment. SR and relapsing rates were subsequently evaluated 6, 12 and 24 months after the end of the treatment, together with those variables capable of predicting SR. RESULTS: At the end of the treatment, 19/77 patients responded (24.7%), 9/63 (14.3%) were non-responders and 10/14 (71.4%) relapsers, and these same patients exhibited SR after 6 months. The SR rate two years after treatment was 22.1% [8/63 (12.7%) NR and 9/14 (64.3%) R]. The relapse rate after 6 months and two years was respectively 0 and 10.5% (2/77). Independent variables capable of predicting SR were negative viremia conversion within the first month of treatment, maintenance of such negative viremia after 6 months, and R status to IFN. Side effects were recorded in 90.9% of cases (70/77), the most frequent being pseudoinfluenza syndrome. Treatment had to be discontinued in 33.8% of patients (26/77). CONCLUSIONS: Combined IFN-RIB therapy for 12 months in CHC patients without SR to IFN obtains a long-term SR of 22.1%, this rate being higher in relapsers to prior IFN therapy (64.3% in R versus 12.7% in NR).

Prevalence of HTLV infection in pregnant women in Spain.

OBJECTIVE: To estimate the prevalence of HTLV infection among pregnant women in Spain. METHODS: A commercial ELISA incorporating HTLV-I and HTLV-II antigens was used for HTLV antibody screening. Repeatedly reactive samples were further examined by western blot. Moreover, confirmation with PCR was performed when cells were available. RESULTS: 20,366 pregnant women in 12 different Spanish cities were tested in a 3 year period (July 1996 to August 1999). 32 samples were repeatedly reactive by ELISA, and 10 of them were confirmed as positive by western blot (eight for HTLV-II and two for HTLV-I). In addition, three of 13 women who had an indeterminate western blot pattern yielded positive results for HTLV-II by PCR. All 11 HTLV-II infected women had been born in Spain, and all but one were former drug users. Seven of them were coinfected with HIV-1. One HTLV-I infected woman was from Peru, where HTLV is endemic and where she most probably was infected during sexual intercourse. CONCLUSION: The overall prevalence of HTLV infection among pregnant women in Spain is 0.064% (13/20,366), and HTLV-II instead of HTLV-I is the most commonly found variant. A strong relation was found among HTLV-II infection and specific epidemiological features, such as Spanish nationality and injecting drug use. Although HTLV-II can be vertically transmitted, mainly through breast feeding, both the low prevalence of infection and its lack of pathogenicity would not support the introduction of HTLV antenatal screening in Spain.

[Prevalence of anti-hepatitis A in patients with chronic liver disease]. / Prevalencia de anti-VHA en pacientes con hepatopatías crónicas.

The recent availability of an effective vaccine for preventing hepatitis A has led to the performance of a prevalence study of antibodies versus the hepatitis A virus (HAV) in our patients with chronic liver disease by hepatitis B and C, as a step prior to vaccination. The sera of 425 patients with a mean age of 40 years was studied, with the global antibodies versus HAV being determined (Abbott). The prevalence was to 75.2% varying from 20% at 19 years to 93% in those over the age of 40. The prevalence was not related to sex, previous parenteral history, or drug addiction or infection by hepatitis B or C. Due to previous cost-benefit studies and the high prevalence found, the determination of anti-HAV in patients with chronic viral liver diseases prior to vaccination against HAV is recommended.

Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain. HTLV Spanish Study Group.

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-I (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.

Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts.

BACKGROUND/METHODS: As a high number of patients with antibodies to hepatitis C (anti-HCV) do not have a known history of parenteral acquisition, other non-parenteral means of hepatitis C virus transmission must be studied. We investigated 1451 household contacts of 535 anti-HCV positive, human immunodeficiency virus-negative index patients. RESULTS: Overall, the prevalence of anti-HCV in household contacts was 4.5%. Thirty (7.6%) out of the 394 heterosexual stable partners were anti-HCV positive as compared to 35 (3.3%) out of 1057 non-sexual contacts (p < 0.01). The prevalence of anti-HCV was lowest in children of the index cases (1.8%). In this group, the prevalence of anti-HCV was 3% (10/330) when the mother was the index case, as opposed to 0.6% (2/328) when the father was the index case (p < 0.05). The prevalence of anti-HCV increased with age, being highest (18.6%) in family contacts older than 60 years. CONCLUSIONS: Transmission of hepatitis C virus may occur among household contacts of anti-HCV positive patients. Sexual contact or the use of non-disposable medical material in the past might explain the higher prevalence of anti-HCV found in sexual partners and in family contacts older than 60 years of age. Anti-HCV screening should be performed in family contacts of anti-HCV positive patients, particularly in those contacts older than 20.

Epidemiology of HIV-2 infection in Spain. The HIV-2 Spanish Study Group.

Human immunodeficiency virus type 2 (HIV-2) infection is endemic in West Africa, where it is responsible for many cases of AIDS. HIV-2-infected subjects have been described in other countries, mainly African immigrants, although infection in native individuals has been reported as well. The first cases of HIV-2 infection in Spain were identified in 1988. Through December 1995, 56 HIV-2 infected individuals have been diagnosed, primarily in large urban areas (23 cases in Madrid and 18 in Barcelona). All are African immigrants, except for 12 natives (21.4%), six of whom acquired the infection in endemic areas; the remaining six (2 women with numerous sexual partners and 4 homo/bisexual men) acquired the infection in Spain. Heterosexual transmission was probable in all but seven cases: five homo/bisexual males, a subject who likely acquired infection through parenteral exposure, and a child born to an HIV-2-infected mother. Nine patients (all Spanish born) have developed AIDS (16%), six of whom have died. In conclusion, HIV-2 infection is present in Spain at a low rate, and there is little evidence supporting an emerging ongoing transmission outside the population of African immigrants.

[HTLV-II infection in Spain. Analysis of 113 cases identified until November, 1994. Spanish Group for the Study of HTLV/I/II]. / Infección por HTLV-II en España. Análisis de 113 casos identificados hasta noviembre de 1994. Grupo Español para el Estudio del HTLV-I/II.

BACKGROUND: HTLV-II is a human retrovirus considered to be responsible for the genesis of some lymphoproliferative and neurologic syndromes. The virus is endemic in some Amerindian and African tribes as well amongst injecting drug addicts (IDA) in North America and Europe. METHODS: The clinical, epidemiologic and virologic characteristics of the patients with HTLV-II infection identified in Spain up to November 1994 are described. RESULTS: One hundred thirteen subjects have been identified with HTLV-II infection in Spain with 4 being African immigrants residing in Madrid and the remaining being IDA from other European countries. Most were males (94/113; 83%). All were IDA except six (5 had acquired the infection by sexual contact and one by blood transfusion). Most of the IDA infected with HTLV-II were coinfected with HIV-1 (93/113; 83%). No patient showed clinical manifestations attributable to HTLV-II infection although one drug addict male coinfected with HIV-1 and HTLV-II developed a non-inflammatory proximal myopathy. CONCLUSIONS: Infection by HTLV-II is present in Spain and affects with preference to injecting drug addicts. It has been shown to be of growing incidence with a current global prevalence of 2% in IDA.

[Evaluation of various criteria for the interpretation of western blot for the diagnosis of human immunodeficiency virus infection. Spanish Group for the Study of HIV-2]. / Evaluación de diferentes criterios de interpretación del Western blot para el diagnóstico de la infección por el virus de la inmunodeficiencia humana. Grupo Español para el Estudio del VIH-2.

BACKGROUND: The Western blot (WB) is the most commonly used test to confirm the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Different criteria of interpretation of the band profile have been proposed with there being no unanimity as to its reliability. The sensitivity and specificity of several criteria proposed for the interpretation of WB were evaluated and the individual significance of the reactivity of each band of the WB was analyzed. METHODS: The presence of antibodies against HIV-1 was prospectively studied in 8,073 samples of subjects with risk of infection. A total of 1,993 (25%) were reactive by ELISA and 1,261 were analyzed by WB, with a semiquantitative reading of the bands with a point scale from 0 to 2 being performed. The final interpretation of the WB (negative, doubtful, or positive) was carried out following 5 recommendations of usage. A test designed with synthetic peptides (Pepti-lav) was used as a reference and in discordant cases, other more specific serologic tests and/or genetic analysis by polymerase chain reaction (PCR) were performed. RESULTS: In order of frequency, the greater sensitivity was found to be for the CRSS (Consortium for Retrovirus Serology Standardization) criteria (97.9%), OMS (96.6%), CDC (Center for Disease Control) (95.9%), ARC (American Red Cross) (95.6%) and FDA (99.8%). The greatest specificity was for the criteria of the OMS, and FDA (99.8%). In order of frequency, the most frequent bands in HIV-1 + individuals were gp160 (99%), gp120, p24, p31, p55, p68, gp41, and p17 (68%). In non infected individuals, the recognized bands were, in decreasing order, p24, p17, p55, p68, p31, and glucoproteins. CONCLUSIONS: Different criteria of interpretation of the Western blot provide different degrees of sensitivity and specificity. The Western blot is a non standardized, expensive, laborious technique of subjective interpretation which provides an appreciable number of undetermined results.

[A multicenter study of infection with human immunodeficiency virus type-2 (HIV-2) in Spain (1991). The Spanish Group for the Study of HIV-2]. / Estudio multicéntrico de la infección por el virus de la inmunodeficiencia humana tipo 2 (VIH-2) en España (1991). Grupo Español para el Estudio del VIH-2.

BACKGROUND: To January 1991 thirteen cases of HIV-2 infection had been reported in Spain. Paradoxically, neighboring countries, i.e. France and Portugal, have reported more than one thousand cases, and are the most HIV-2 prevalent areas outside West Africa. We report the results of a prospective, nationwide study on the prevalence of HIV-2 infection conducted in Spain in 1991. In addition, an evaluation of testing methodologies is made. METHODS: Sera collected from 8,073 individuals at high-risk for HIV infection were screened by a combined HIV-1 plus HIV-2 ELISA. Reactive samples were further evaluated by three tests, as HIV-1 Western blot (WB), HIV-2 specific WB, and a synthetic peptide assay immuno-dot (Pepti-lav, Pasteur). RESULTS: Fifteen (0.18%) individuals met criteria of HIV-2 infection in both specific WB and SPA. Four (27%) of them showed reactivity to both HIV-1 and HIV-2, and the dual infection was confirmed by polymerase chain reaction (PCR) in 2 out of 3 available samples. The SPA showed higher sensitivity and specificity than WB in the diagnosis and distinction of HIV-1 and HIV-2 infections. CONCLUSIONS: To January 1992, 28 cases of HIV-2 infection have been described in Spain. All but two were African immigrants. The first cases of HIV-1 plus HIV-2 coinfection have been identified. In HIV high-risk populations, SPA may provide an excellent alternative to WB to confirm ELISA reactive samples.