Is HCV transmitted by the vertical/perinatal route?

Hepatitis type C is the major aetiological cause of both parenterally transmitted and cryptogenic, sporadic or community acquired nonAnonB hepatitis. The lack of known parenteral risk factors in a consistent number of cases with nonAnonB hepatitis has stimulated the search of other possible modes of viral transmission. The aim of this report is to review the evidence both for and against vertical/perinatal transmission of HCV from anti-HCV positive mothers to infants.

[Survey of the use of vaccination against measles and pertussis in a city of the Milanese hinterland]. / Inchiesta sulla applicazione delle vaccinazioni contro la pertosse e contro il morbillo in una citta dell'hinterland Milanese.

In april 1986 a questionnaire was submitted to the mothers of a randomized sample of children born in 1984 in a city of the hinterland of Milan. The aim of the investigation was to get information on the level of knowledge of the population on pertussis and measles diseases and on pertussis and measles vaccinations that are optional in our country. The mothers were also asked to specify the reasons of not having vaccinated their children. Aut of 146 questionnaires distributed, 137 (93%) were filled. According to the mother's recall, 22 (16%) children had been vaccinated against pertussis and 36 (26%) against measles. On the whole, the results indicate that the lack of pertussis and measles vaccinations was mainly due to ignorance about the diseases and about the vaccines. Indeed, the reasons for the lack of vaccination most frequently given by the mothers were: " belief that a child msut get these diseases" (23% of the answers for pertussis and 36% for measles), " ignorance of the availability of vaccines " (32% for anti-pertussis and 16% for anti-measles vaccination); "poor knowledge on the facilities in which to get child vaccinated" (23% for anti-pertussis and 16% for anti-measles vaccination). Moreover, on the total of the 137 interviewed mothers only 37% and 56%, respectively, knew that natural pertussis and natural measles may be accompanied or followed by complications. The frequency of the various answers was rather homogeneous regardless of the mother's schooling and of mother being a house-wife or working outside the home. It is therefore concluded that to obtain a satisfactory compliance to measles and pertussis vaccinations, it is necessary to educate parents and to improve their knowledge of the diseases and of the benefits of the vaccines.

[Characteristics of the virus and of measles vaccines (author's transl)]. / Generalità sul virus del morbillo e sui relativi vaccini.

Characteristics of measles virus and some aspects of virus-cell interaction are reported. For their interest, findings from recents investigations on comparison between SSPE isolates and wild strains are summarized. Both inactivated and live attenuated measles vaccines are then briefly described. The former has been used in the U.S.A. from 1963 to 1968 and discontinued thereafter mainly for safety problems, the latter, prepared with Schwarz or with Moraten strain, are in use today for the prophylaxis against measles.

Anti-neuraminidase antibody response in hamsters experimentally infected with Sendai virus.

Investigations were performed to study the behaviour of neuraminidase-inhibiting (n.i.a.) and, by comparison, of neutralizing, hemagglutinin-inhibiting (h.i.a.) and anti-S and anti-V complement-fixing (c.f.a.) antibodies in hamsters inoculated intranasally with a Sendai virus strain of recent isolation. Moreover the distribution of the virus in the respiratory tract was followed. Preliminary experiences were done to assure a correct performance of the neuraminidase-inhibition test. First of all the optimal pH and then the influence of the normal hamster serum on the enzyme activity were evaluated. The n.i.a. as well as h.i.a. and anti-S and anti-V c.f.a. were demonstrable from day 6th after infection, neutralizing antibody from 8th day. The n.i.a. reached the peak of 24 days, that is later than the other types of antibodies, and started to decline after 1 month, together with the drop of the h.i.a and c.f.a. On the contrary the neutralizing antibody persisted at high titres till the end of the observation period (75 days). Detectable antibody response was coincidental with a marked drop in the titers of virus recovered from the respiratory tract. Because of the association of both hemagglutinating and neuraminidase activities with the same Sendai glycoprotein, it is stressed the possibility that hemagglutination-inhibition and neutraminidase-inibition tests titrate the same antibody.

Relative antigenicity in mice of H1N1, H3N2 and B strains present in inactivated influenza virus vaccines.

The results of a study on serum HAI and neutralizing antibodies induced in mice by whole influenza virus vaccines containing A/Brazil/11/78 (H1N1), A/Bangkok/1/79 (H3N2) and B/Singapore/222/79 viruses are reported. According to the GMT of HAI, the antigenic potency of the three vaccine strains appear to be different. The A/Brazil/11/78 antigen induced the lowest HAI antibody responses and the A/Bangkok/1/79 antigen the greatest. This behaviour, with a few exceptions, was noted regardless of the HA amount (0.08 microgram 0.4 microgram, 2 micrograms) of each strain present in the vaccine, the number of doses (one or two), or the kind of preparation (monovalent or trivalent). The data obtained with the neutralization test with vaccines with medium HA content are concordant with previous findings. On the basis of the ratios of the GMT of the neutralizing antibodies to the GMT of the HAI antibodies, it was concluded that the HAI antibodies to A/Bangkok/1/79 antigen possess, on the whole, a neutralizing activity that is higher than that found for the HAI antibodies to A/Brazil/11/78 and B/Singapore/222/79 strains. For the latter strains, the neutralizing activity increased after the second dose. The observation of the different degrees of antigenicity of the three vaccine strains suggests that, with currently used inactivated influenza virus vaccines containing equivalent amounts of all three antigens, the dosage should be taken into consideration when the vaccines are used for subjects lacking in previous exposure to vaccine strains.

Serological evidence of human infections with avian influenza viruses. Brief report.

Two hundred ninety-four subjects from Milan were tested for serum hemagglutination-inhibiting (HI) and neuraminidase-inhibiting (NI) antibodies to five avian influenza viruses. No HI antibodies were found in all the serum samples. On the contrary, NI antibodies to each strain were detected depending on the year of birth of the subjects.

[Neutralizing and inhibiting activity of hemagglutination of serum antibodies after natural infection and after vaccination with influenza virus A/USSR/90/77 (H1N1) strain]. / Attività neutralizzante ed inibente l'emoagglutinazione degli anticorpi sierici dopo infezione naturale e dopo vaccinazione con lo stipite di virus influenzale A/USSR/90/77 (H1N1).

Sera with different content of hemagglutination-inhibiting antibody (h.i.a.) collected from healthy subjects in late summer 1978, from influenza cases which occurred in winters 1977-78 and 1978-79 and from vaccinees in autumn 1978 were checked for neutralizing antibodies (n.a.) to A/USSR/90/77 influenza virus strain. Neutralizing activity (Geometric mean titer of n.a.) of h.i.a. was found dependent chiefly on the previous antigenic experience of the subjects. This because, given the same h.i.a. level, geometric mean titers of n.a. were lower in children and adolescents than in adults more than 24-year-old. For the age of the subjects and for time of collection of sera, the presence of antibodies in the former group is very likely due to the first antigenic stimulus. Moreover among the vaccinated adults the Geometric mean titers of n.a. in sera with the same h.i.a. content were higher in the age group 25-40 years. With any probability this is the cohort with an original antigenic sin due to H1N1 variants. The results have been also discussed in relation to the epidemiological behaviour of H1N1 strains in the first years of the second prevalence era. The above observations suggest caution in adopting the only hemagglutination-inhibition test for evaluating the immune status of populations and the immunizing efficacy of influenza virus vaccines.

[Age of measles vaccination in Lombardy from the results of a seroepidemiological survey in Milan]. / Indicazioni sull'eta' di applicazione della vaccinazione antimorbillo in Lombardia come risulta da una indagine sieroepidemiologica effettuata a Milano.

In view of the introduction of measles vaccination in Lombardy and since the age of vaccination is of paramount importance, measles h.i.a. were titrated in sera from 209 children between 0 and 6 years of age (of whom 171/0--2) and from 40 woman in the child-bearing age. As it could be expected from the high prevalence of adults with antibody (95%), 90% of umbelical cord sera have h.ia.,, Over 50% of children 15 days-3 months of age are still positive and afterwards the positivity decreases progressivley till a minimum of 8% in children 10--12 months old. Beginning with the second year of life the percentage of immune children grows slowly to reach 50% in the age group 3--6 years. The distribution of antibody titers between 6 and 12 months, time at which maternal antibody are largely waned, suggested that the infection with measles virus is a rare event in the first year of life, while a substantial number of children gets the infection between 18 and 24 months. From these results it appears that also in Lombardy measles vaccination should be given not before 13 months and not after 18 months of age.

[Prevalence of antibodies to A/New Jersey/76, A/Victoria/3/75 and B/Hong Kong/5/72 influenza viruses in the population of Milan examined in the late spring of 1976 and evaluation of the past experience of the same population with probable agent of the 1918-20 pandemics]. / Prevalenza degli anticorpi verso i virus influenzali A/New Jersey/76, A/Victoria/3/75 e B/Hong Kong/5/72 nella popolazione milanese esaminata nella tarda primavera 1976 e valutazione dell'esperienza della popolazione in istudio nei confronti del probabile agente della pandemia del 1918-20

Hemagglutination inhibiting antibodies (h.i.a.) to influenza viruses A/New Jersey/76, A/Victoria/3/75 and B/Hong Kong/5/72 were titrated in 227 serum samples collected in Milan in the late spring 1976 from healthy subjects of 0 to 90 years of age. In 185 of these neuraminidase-inhibiting antibodies (n.i.a.) for the type A strains were also titrated. Subjects up to 40 years of age lack h.i.a. to A/New Jersey/76 strain; antibody levels equal to or greater than 1:40 are occasionally present in the 41-50 year group and the incidence rises to 75% and more after 60 years. N.i.a. are absent in the sera from persons of 0-30 years and titers equal to or greater than 1:100 were found only in the age group over 40. Of the sera examined 44% is lacking in h.i.a. to A/Victoria/3/75 strain and antibodies at protective levels were found in 14% of the subjects, usually among the youngest (0-15 years) and the elderly (over 60 years). N.i.a. for this strain are present in 40% of the samples and 10% have titers equal to or greater than 1.100. Half of the sera under test has h.i.a. to B/Hong Kong/5/72 strain, but only 19% with titers equal to or greater than 1:40. The age distribution of h.i. and n.i. antibodies to A/New Jersey/76 virus suggests that strains antigenically related to the swine virus were widespread in our population until about 1929. The presence of n.i.a., but not of h.i.a. in subjects born between 1935 and 1946 supports the hypothesis of cross-reaction between the neuraminidases of the swine and of the A-O strains.

[Capacity of anti-influenza subunit vaccines to elicit the formation of heterologous antibodies]. / Capacita' dei vaccini antiinfluenzali contenenti sub-unita' nell'indurre la formazione di anticorpi eteologhi.

The hemoagglutination-inhibiting antibody (h.i.a) response to A/Brazil/11/78 (H1 N1), A/Bangkok/1/79 (H3 N2) and B/Singapore/222/79 strains was evaluated in children and adults after administration of trivalent A/USSR/ 90/77 (H1 N1), A/Texas/1/77 (H3 N2), B/Hong Kong/8/73 influenza vaccines, two containing sub-unit and one whole virus. For each group of vaccinees, the behaviour of heterologous h.i.a. was compared to that of homologous antibodies. The rates of titer increases and the post-vaccinal geometric mean titers indicate that sub-unit vaccines are as immunogenic as whole virus vaccine in evoking heterologous antibodies. The greater difference between homologous and heterologous h.i.a. titers was found in adults for H3 N2 strains, the smaller for H1 N1 viruses. For the latter strains low post-vaccinal h.i.a. levels have been observed in all groups of vaccinees. In this regard the hypothesis has been put forward that immunogenicity of vaccines may be dependent on some intrinsic virus properties.

HIV antibody screening and confirmatory testing of Italian blood donors. One-year experience of a reference center.

During the first year (1986) of blood donor screening for antibody to HIV, 201,750 subjects were tested in 40 blood banks of Lombardia (Italy). All sera repeatedly positive by ELISA were submitted to our reference center for confirmation by Western blot (WB). Only 40 (0.02%) of 286 repeatedly reactive donors were positive by WB, whereas another 45 (0.022%) gave atypical antibody reactivities on WB, mainly directed against HIV core proteins. Of the 16 donors with inconclusive WB results followed for 4-12 months, 3 developed a full-blown antibody response, 5 maintained the anti-core reactivity throughout the follow-up period, and 8 lost all reactivities. The use of recombinant env and core antigen ELISAs seems to decrease the proportion of sera with inconclusive WB reactions, and to identify as true positive all seroconverting donors in advance of the WB test. The large majority (35 out of 40) of WB-positive donors and all seroconverters for antibody to HIV admitted to belong to a group at risk for AIDS. Among the 19 first-time donors with HIV infection, we found 3 subjects with serological evidence of LAV-2 infection. We describe also the diagnostic and ethical issues when a donor notification policy is based on WB confirmatory procedures.

A survey on factors affecting acceptance of measles vaccine.

The reasons for the low level of acceptance of measles vaccine were investigated through interviews with the mothers at the time of their children enrollment in the first year of attendance at several nursery schools in Milan city and its suburbs. Data were also collected on the natural disease. Only 192 (13.8%) of the 1386 children included in the study had already suffered natural measles and 45 of them before the age of 12 months. Of the total, 10% of the children had been vaccinated, more in the city of Milan than in the suburbs. Approximately one-half of the vaccinations had been administered by family doctors and the other half in Public Health facilities. Less than half of the vaccinations administered in the city of Milan proved to have been registered in Public Health Office records. The frequency of vaccinated children was significantly higher among mother with higher levels of education than among those with lower levels of education. The reasons for the lack of vaccination most frequently given by the mothers of the 1247 unvaccinated children were "ignorance about the vaccine" (38% of the mothers) and the "belief that measles is an innocuous disease" (36%). These were followed by "fear of post-vaccinal reactions" and "advice against measles vaccine" given, in most cases, by family doctors. The frequency of responses for each one of these reasons was significantly different in Milan with respect to the suburbs. This difference was also evident in the comparisons between mothers with higher levels of education with respect to mothers with low levels of education.

[Relation between serologic verification and anamnestic data on the principal virus diseases of infancy]. / Correlazione tra riscontri sierologici e dati anamnestici nell'ambito delle principali malattie virali dell'infanzia.

Serologic status of about 300 subjects (age: 2-15 years) for measles, rubella, varicella and mumps was compared with the anamnestic recall of their mothers. Measles, rubella and varicella antibodies were determined by ELISA methods. Mumps antibodies were titrated by hemagglutination-inhibition test. Serology agreed with the clinical history of the subject in 83% of the cases for measles, in 69% for rubella, in 87% for varicella and in 82% for mumps. The frequency of seronegative subjects who were reported to have had the disease was low (less than 8%) for each of the four viruses. The opposite situation was found in the 8% of the subjects for measles, in 23% for rubella, in 10% for varicella and in 13% for mumps. In general there was no significant difference in the rate of disagreements between serology and history of the disease in relation to mothers' schooling and occupation (house wives or mothers who work outside the home). Geometric mean titers of hemagglutination-inhibiting antibody to mumps virus sharply declined 3-4 years after the disease and stabilized thereafter. Prevalence of antibodies according to age shows that measles, rubella and varicella antibodies are acquired early in life, while 29% of the subjects 14-15 years of age still lacked mumps antibodies.

[An influenza outbreak of type A and type B influenza viruses]. / Osservazioni su di un episodio epidemico da virus influenzali di tipo A e di tipo B.

Results of investigations carried out during an outbreak of influenza occurred in January 1981 in a School of Milan are reported and discussed. A total of 9 type A (H1N1) influenza virus strains, antigenically intermediate between A/USSR/90/77 and A/Brazil/11/78 variants, and 2 type B influenza virus strains, antigenically intermediate between B/Hong Kong/8/73 and B/Singapore/222/79 variants, have been isolated. In one case both epidemic strains have been simultaneously detected. From the results of type-specific complement-fixing antibody titration it appears that an influenza virus infection occurred in 64% of the 300 subjects serologically examined. In 43% of the cases type A strain was involved, in 12% type B strain and in 9% both serotypes. Judging from the data of school absenteeism it seems that infections by type A virus were more severe than those by type B virus. Finally, because a group of pupils attending the school had been vaccinated in December 1978, it has been demonstrated that the rate of type A presumptive infections was correlated to the hemagglutination-inhibiting antibody titers attained after vaccination.

[Incidence of hemagglutination-inhibiting antibodies in the population of Milan and of Bari against strains of influenza viruses of epidemiological importance in the winter of 1977-78]. / Incidenza degli anticorpi inibenti l'emoagglutinazione nelle popolazioni di Milano e di Bari verso i ceppi di virus influenzali d'importanza epidemiologica per l'inverno 1977-78.

A sero-epidemiological survey was carried out on 555 serum samples from normal subjects of both sexes (age: from few months to over 60 years) collected in the late summer 1977 in Milan and Bari, two towns with rather different climatic conditions. In both localities a further large spread of A/Victoria/3/75 strain seems unlikely, since 54% of sera from Milan and 58% of those from Bari have h.i.a. at protective titers. On the contrary, the degree of immunity against B/Hong Kong/8/73 virus is still faiitical level for the survival of A/Hong Kong/68 pandemic strain appears almost reached in the population of Milan, where 76% of subjects have antibody at protective titers. In Bari such percentage is 60%. The statistical analysis (X2 test) of the data concerning the subjects with h.i.a. at titers greater than or equal to 1:40 shows only one significant difference between Milan and Bari, that is the A/Hong Kong/68 antibody prevalence. Probably this is due to the low number of males of Bari with protective antibody levels.

[Role of the virologic laboratory in the diagnosis of subacute sclerosing panencephalitis. Report of 12 cases studied between May, 1977 and March, 1978]. / Il ruolo del laboratorio virologico nella diagnosi della PESS. Osservazioni su 12 casi studiati tra il maggio 1977 ed il marzo 1978.

Measles h.i.a. and c.f.a. were titrated in serum and cerebrospinal fluid of 12 SSPE patients. Specific IgM h.i.a. in the same specimens were also determined. Pretreatment of the sera by monkey red blood cell absorption, by kaolin or by heparin MnCl2, did not significantly affect h.i.a. titres, but h.i.a. were no more demonstrable in cerebrospinal fluids after kaolin and titres were somewhat lowered by heparin-MnCl2 treatment. By both h.i. and c.f. tests measles antibody were found at much higher titres in sera of SSPE patients than in controls of the same age. H.i.a. and, with one exception, c.f.a. were found in each of the 9 available cerebrospinal fluids from patients, but in none of the 6 specimens from non-SSPE cases. Ratio GM titers h.i.a. over GM titers c.f.a. in sera of SSPE patients was about 1, a value far from that found under different immunization conditions. In control sera, for instance, the ratio was 5.3. Specific IgM were never found in the cerebrospinal fluids and in only 2 out of the 10 sera examined.

[Serologic survey of human type A influenza virus infection following 10-year periods of prevalence of H3N2 strains]. / Ricapitolazione sierologica delle passate infezioni con virus influenzali di tipo A dopo circa un decennio di prevalenza degli stipiti H3N2.

Distribution of h.i.a. against A/New Jersey/8/76 (Hsw1N1), A/PR/8/34 (H0N1), A/FM/1/47 (H1N1), A/Japan/305/57 (H2N2) influenza virus strains was determined in 553 serum samples, previously tested for A/Hong Kong/1/68 virus, collected in the late summer of 1977 in Milan and Bari. For all variants, distinctive antibody patterns were obtained which reflect periods of prevalence of these viruses in man. So, the peak of positivity and the higher h.i.a. levels were found for A/New Jersey/8/76 strain in subjects born between 1907 and 1916, in the case of A/PR/8/34 virus for the birth years 1927-36, ten years later (1937-46) for A/FM/1/47 strain and for A/Japan/305/57 and A/Hong Kong/1/68 variants respectively for the birth years 1947-56 and 1962-66. The presence of antibodies to influenza A viruses not supposed to have been current during the person's lifetime has been discussed.

[Optimal temperature of enzyme activity and heat resistance of neuraminidases as attenuation markers for influenza viruses]. / Temperatura ottimale d'attivita' enzimatica e termoresistenza della neuraminidasi come marcatori di attenuazione per i virus influenzali.

Neuraminidase activity of virulent and vaccinal strains A/England/42/72, A/Scotland/840/74 and A/Victoria/3/75 assessed at different temperatures did not show significant differences in the temperature optima of enzyme activity. Vaccinal strains were attenuated by APR-8 recombination and selection of mutants resistant to serum inhibitors (Alice, RIT 4025, RIT 4050 strains). On the contrary, differences were found in the thermal inactivation of the neuraminidase between wild and vaccinal strains, the latter being more thermolabile. Increasing from 0.5 to 5.0 mM/1 the Ca++ concentration, an enhancement of the heat stability was observed, more marked for the attenuated strains. The amount of NANA released by 1 hemagglutinating unit varied widely between strains. To be pointed out, however, that within each antigenic variant the vaccinal strain showed a lower enzymatic activity than the corresponding wild strain.

A seroepidemiologic survey of immunity against poliomyelitis in a group of HIV positive and HIV negative drug addicts.

In a seroepidemiological study performed to investigate immunity against poliomyelitis in a population of drug addicts in a rehabilitative residential centre we demonstrated a widespread lack of poliovirus neutralizing antibodies. This was more evident in the HIV positive subjects, 27% of whom were seronegative for poliovirus type 1, 27% for type 2 and 34% for type 3, with 11% seronegative for all three types. These results indicate a gap in immunity to poliomyelitis in the examined population.