Influenza subunit vaccine: antibody responses to one and two doses of vaccine and length of response,with particular reference to the elderly.

Antibody responses to subunit influenza vaccine prepared against A2/England/42/72 (h3n2) were studied in 69 volunteers aged 60 and over and 231 aged 59 and below over 12 months in 1973 and 1974. After two doses of vaccine seroconversion frequencies and geometric mean haemagglutination-inhibition (HI) titres were higher in the elderly, but no differences were observed between the two groups in the length of their responses. Sixteen (23%) of the elderly volunteers seroconverted only after receiving a second dose of vaccine or seroconverted twice after receiving both doses of vaccine. It was considered justifiable, therefore, to recommend the continuation of a two-dose schedule for patients in a high-risk category. Within 30 weeks of vaccination 87 (29%) volunteers had considerably reduced HI titres (less than 48), which might indicate potential susceptibility to influenza during an epidemic, and the number had risen to 132 (44%) by 50 weeks. It was suggested that high-risk patients should receive annnual vaccination two to four months before the possible epidemic period.     

Influence of haemoglobin type and selenium status on peripheral plasma progesterone and corticosteroid concentration in ewes grazing oestrogenic pastures.

Peripheral plasma progesterone and corticosteroid concentrations were studied in ewes grazing oestrogenic pastures during oestrus, pregnancy and parturition in 1974 and during pregnancy in 1975. Haemoglobin (Hb) type A ewes had significantly higher mean corticosteroid concentrations than HbB ewes in both years. In 1974 the concentration of progesterone did not differ significantly between Hb types whilst in 1975 the concentration was significantly (P less than 0.001) higher in HbA ewes. The mean corticosteroid concentrations were higher in selenium-supplemented ewes of both Hb types than in unsupplemented ewes in 1974 but lower in 1975. Selenium treatment did not significantly influence the progesterone concentration in ewes of both Hb types in 1974 but significantly (P less than 0.01) increased in 1975. It is concluded that the higher concentration of plasma corticosteroids or factors regulating the relationship between corticosteroids and progesterone could be responsible for the higher estimates of embryonic mortality reported in HbA ewes.     

Control of adenovirus acute respiratory disease in U.S. Army trainees.

Although limited almost exclusively to military trainees, acute respiratory disease (ARD) caused by adenovirus types 4 and 7 had been the leading cause of hospitalization in U.S. Army personnel. This decrease which resembles influenza in clinical manifestations led to hospitalization of as many as 50% of military trainees in midwinter and imposed a heavy burden on military hospitals and training programs. In studies undertaken from 1965 to 1970, live adenovirus type 4 and subsequently type 7 vaccines were found to be safe and immunogenic and to confer protection against type specific adenovirus ARD. For the past 5 yr. military trainees have been immunized with both adenovirus vaccines during periods of expected adenovirus disease. Since 1966, use of adenovirus vaccines has been monitored through the adenovirus surveillance program which yields weekly data on incidence and etiology of ARD in basic combat trainees. Since 1973, stable adenovirus vaccines have resulted in excellent control of adenovirus ARD. Potential problems with this immunization program are discussed.     

Staphylococcal opsonization and anti-Staphylococcus aureus IgG subclass antibodies in patients with severe or recurrent S. aureus infections

Opsonization of Staphylococcus aureus (Oxford strain) and specific IgG subclass antibodies against formalised staphylococci were measured in plasmas from 27 patients with significant S. aureus infections and 35 healthy adults and 15 children. There were no statistically significant differences in the IgG2 and IgG4 levels between two groups and IgG3 was not detected, but the median plasma IgG1 level was significantly higher in patients with staphylococcal infections (P less than 0.00003). The concentration of IgG2 anti-S. aureus antibodies was 25-47 times greater than that of IgG1. If plasmas were decomplemented, the raised IgG1 levels were associated with increased opsonophagocytosis by normal neutrophils (P less than 0.0002).     

Forecasting barley mildew development in West Scotland

Observations on plots of spring barley cv. Golden Promise during May-July 1973–79 showed that escalation of mildew commenced in mid-June 1976, in late June in 1973 and 1974, in early July in 1978 and 1979, and failed to develop in 1975 and 1977. By mid-July there was 40% infection in 1976, and 13–21% infection in 1973, 1974, 1978 and 1979. Less than 2% mildew occurred in 1975 and 1977. Using as a basis the method of mildew forecasting formulated by Polley & King (1973), it was found that once mildew was established in the crop there was moderately good association between the incidence of high mildew risk according to the Polley weather criteria and the major peaks of spore concentration above the crops. It was not possible to correlate these two features during May and early June each year because of a lack of inoculum, but it is considered that the failure of mildew to develop during the entire growing seasons of 1975 and 1977, in spite of frequent high risk periods, was due in part to low atmospheric humidity during the early part of the season. The relative number of accumulated Polley factors satisfied on days when the relative humidity approx. 1 m above ground was 78% or more (at 0900 GMT) during the period mid-May to mid-June, separated the low mildew years of 1975 and 1977 from the moderate ones of 1973, 1974, 1978 and 1979, and the severe mildew year of 1976. This procedure may provide a practical means of forecasting the level of mildew build-up during the later growth stages of the barley crop.     

Serological evidence of inter-epidemic infection of feral pigs in New South Wales with Murray Valley encephalitis virus.

The sera of 617 feral pigs, collected from three widely separated areas of northern and central New South Wales, were examined for antibody to Murray Valley encephalitis (MVE) virus and to Ross River virus. Haemagglutination-inhibition (HI) antibody was detected to MVE in 58% of sera and to Ross River virus in 15% of sera. Neutralization tests suggested that the MVE HI antibody resulted from infection with MVE virus in the summers of 1971-1972 and 1972-1973 when the virus was not known to be active in New South Wales. These same tests suggested that more than one flavivirus infected the feral pigs in the summer of 1973-1974 and that Kunjin virus was active in the summer of 1975-1976.     

Acute viral infections of upper respiratory tract in elderly people living in the community: comparative,prospective, population based study of disease burden.

OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.     

Staphylococcal opsonization and anti-Staphylococcus aureus IgG subclass antibodies in patients with severe or recurrent S. aureus infections

Abstract Opsonization of Staphylococcus aureus (Oxford strain) and specific IgG subclass antibodies against formalised staphylococci were meausred in plamas from 27 patients with significant S. aureus infections and 35 healty adults and 15 children. There were no statistically significant differences in the IgG2 and IgG4 levels between two groups and IgG3 was not detected, but the median plasma IgG1 level was significantly higher in patients with staphylococcal infections ( P < 0.00003). The concentration of IgG2 anti- S. aureus antibodies was 25–47 times greater than that of IgG1. If plasmas were decomplemented, the raised IgG1 levels were associated with increased opsonophagocytosis by normal neutrophils ( P < 0.0002).     

Heterosubtype Neutralizing Responses to Influenza A (H5N1) Viruses Are Mediated by Antibodies to Virus Haemagglutinin

Background

It is increasingly clear that influenza A infection induces cross-subtype neutralizing antibodies that may potentially confer protection against zoonotic infections. It is unclear whether this is mediated by antibodies to the neuraminidase (NA) or haemagglutinin (HA). We use pseudoviral particles (H5pp) coated with H5 haemagglutinin but not N1 neuraminidase to address this question. In this study, we investigate whether cross-neutralizing antibodies in persons unexposed to H5N1 is reactive to the H5 haemagglutinin.

Methodology/Principal Findings

We measured H5-neutralization antibody titers pre- and post-vaccination using the H5N1 micro-neutralization test (MN) and H5pp tests in subjects given seasonal vaccines and in selected sera from European elderly volunteers in a H5N1 vaccine trial who had detectable pre-vaccination H5N1 MN antibody titers. We found detectable (titer ≥20) H5N1 neutralizing antibodies in a minority of pre-seasonal vaccine sera and evidence of a serological response to H5N1 in others after seasonal influenza vaccination. There was excellent correlation in the antibody titers between the H5N1 MN and H5pp tests. Similar correlations were found between MN and H5pp in the pre-vaccine sera from the cohort of H5N1 vaccine trial recipients.

Conclusions/Significance

Heterosubtype neutralizing antibody to H5N1 in healthy volunteers unexposed to H5N1 is mediated by cross-reaction to the H5 haemagglutinin.     

Letter: Spontaneous pelvic thrombosis in the postmenopausal woman.

An epidemic of rubella reached its peak in the Atlantic provinces in 1974, subsiding in early 1975. With the exception of Quebec the remainder of Canada showed a reverse trend, with a large increase in the numbers of cases reported in the first 41/2 months of 1975. The Halifax virus laboratory reported 106 serologically proven cases of rubella in 1974, 44 of them in pregnant women. In the aftermath of the epidemic many infants were born with the congenital rubella syndrome (CRS). A study carried out from Sept. 1, 1974 through Apr. 30, 1975 showed an 80% correlation between clinical diagnosis and the presence of rubella-specific IgM antibodies in 35 of these infants. Of the 23 infants in whom the diagnosis of CRS was made by laboratory or clinical findings or both, laboratory criteria were met in 20 (87.0%), clinical criteria in 19 (82.6%) and both laboratory and clinical criteria in 16 (69.6%).     

Respiratory viruses and sudden infant death.

Viruses were shown to be present in the respiratory tract in 200 of 763 cases of the sudden infant death syndrome studied in the nine years 1974-82. Epidemiological and pathological evidence suggested that the distribution of viruses in the sudden infant death syndrome differs between infants aged 3 months or less and those aged over 3 months: the incidence of detection of virus was 14% in the younger group compared with 39% in the older group. The distribution of the viruses in these two groups was compared with that in 1341 live infants with respiratory virus infections. Adenovirus, influenza virus, parainfluenza virus, and rhinovirus had similar distribution among the victims of the sudden infant death syndrome and live controls. The incidence of detection of respiratory syncytial virus was increased in the older infants dying of the sudden infant death syndrome (90% of the cases detected) compared with the older group of live infants (53%). Antibody studies, detection of virus, and epidemiological data suggest that respiratory syncytial virus may be a precipitating factor of sudden death in older infants.     

A summary of the prevalence of Parelaphostrongylus tenuis in a captive wapiti population.

A total of 87 brains from harvested and collected wapiti and red deer (Cervus spp.) were examined grossly and microscopically between 1973 and 1977 in a 2104 ha. preserve. Prevalence of infection significantly increased from 26.6% of the sample in 1973 to 64.3% in 1975 (P less than .05). A decline to 47.7% in 1977 (P greater than .05) was not significant. However, the number of clinical cases was significantly higher in 1976-1977 (P less than .02) than previously reported in 1973-1975.     

The use of influenza vaccines and remantadine for protection against influenza in industrial enterprises

The effectiveness of inactivated and live influenza vaccines and remantidin was studied in persons with different annual morbidity rate in influenza and acute respiratory diseases (ARD). After three and more years of immunization with the inactivated vaccine the number of seroconversions to viruses A (H1N1) and A (H3N2) in vaccinees decreased, respectively, from 75.0 to 26.0% and from 79.3 to 38.8%, and after an interval of two years or the alternation of inactivated and live vaccines the number of seroconversions increased to 57.9-64.0%. The significant decrease of morbidity rate in influenza and ARD were observed only in persons, having had frequent ARD in their medical history and immunized with live and inactivated vaccines simultaneously or separately with the alternation of these vaccines every year (the effectiveness index being equal to 1.7-1.8). At the period of epidemic the controlled administration of remantadin to persons with contraindications to immunization ensured the decrease of morbidity rate in influenza 1.5-1.8 times; in vaccinees, highly susceptible to ARD, the administration of remantadin decreased morbidity rate 2.3 times.     

Haemagglutination-inhibiting antibodies against influenza A and B in human sera collected from five ecological zones in Nigeria.

The prevalence of antibodies to the haemagglutinins of two influenza A subtype, H1N1 and H3N2 and influenza B in sera collected from 1986 to 1988 from persons of different ages and from 10 locations in 5 ecological zones of Nigeria was determined. The levels of influenza antibodies in the sera varies with age and ecological zones of the country. A total of 1,022 sera were tested, of which 732 (71.6%) were positive for influenza antibodies. The prevalence of antibodies at titre 1:10 varied between 31.1% in the derived savannah and 94.4% in the swamp forest. The prevalence in the other zones were: rain forest 63.9%, guinea savannah 86.0% and 78.0% in sudan savannah. Reactors with the two influenza A subtypes antigens were more than reactors with influenza B antigens in the country. Antibody levels to influenza A subtypes varied between and within zones. Although there was no significant difference a (P greater than 0.05) in the overall prevalence of antibodies to the two subtypes, more sera had haemagglutination-inhibiting antibody to H1N1 subtype than H3N2 subtype in all the zones except in the rain forest. Prevalence of antibodies to influenza viruses increased with age in all the zones. Overcrowding in big cities and dry, dusty harmattan weather of the northern parts of the country are considered as possible risk factors in the epidemiology of influenza in Nigeria.     

Immuno-pathotyping of Karnal bunt (Tilletia indica) isolates of wheat using anti-mycelial antibodies

Two types of polyclonal antibodies raised against whole lyophilized (LMA) and fractionated mycelial antigen (FMA) of most virulent, Pantnagar isolate of T. indica were used for the development of immunoassay systems, viz. dot immuno-binding assay (DIBA) and indirect enzyme linked immuno-sorbent assay (ELISA) procedures. The immuno-assays were developed by performing antigen concentration kinetics and antibody dilution curves analyses. These assays were employed for immuno-analysis of diversity amongst KB pathogen based on antibodies reactivity pattern and subsequently categorization into distinct sero-groups. The reactivity of two polyclonal antibodies was tested with 15 (P1-P15) isolates of T. indica. When anti-LMA antibodies were tested, four serologically distinct groups were formed based on percent reactivity (>75%, highly reactive; 60-75%; moderately reactive, <50-25%; low reactive and <25%, non-reactive). However, when anti-FMA antibodies were used, two distinct sero-groups were formed based on reactivity patterns (group I, highly reactive P1, P3, P4, P11 and P13, group II, less reactive P2, P4, P5, P6, P7, P8, P9, P10, P12, P14 and P15).     

Protection of Man from Natural Infection with Influenza A2 Hong Kong Virus by Amantadine: A Controlled Field Trial

Prophylactic administration of amantadine in doses of 100 mg. twice a day offered statistically significant protection against influenza A2 infection in a double-blind field trial involving 391 medical student volunteers during the influenza A2 Hong Kong epidemic in Helsinki in the winter of 1969. Serologically verified influenza, as measured by complement fixation and/or haemagglutination inhibition, occurred in 27 out of 192 students in the amantadine group against 57 out of 199 in the placebo group, giving a protection rate of 52%.     

Virus specificity of human influenza virus-immune cytotoxic T cells.

The virus specificity of human in vitro cytotoxic T cell responses to influenza virus was studied with the use of peripheral blood mononuclear leukocytes from normal adult volunteers. Previous natural exposure of these donors to a variety of type A influenza viruses was documented by HI antibody titers. Cells sensitized in vitro with A/HK or A/PR8 were cytotoxic for autologous target cells infected with A/HK, A/PR8, or A/JAP 305 type A influenza viruses, but not for B/HK-infected or uninfected cells. B/HK-sensitized effector cells lysed target cells infected with B/HK but not targets infected with type A viruses. A/HK- and A/PR8-immune effector populations were shown to recognize cross-reactive antigens on A/HK- and A/PR8-infected target cells by cold target competition. Influenza-immune effector cells were cytotoxic for virus-infected autologous targets but much less so for virus-infected allogeneic targets. This self-restriction suggested that the cytotoxicity was largely T cell-mediated and was confirmed by cell separation analysis. Thus, the human secondary cytotoxic T cell response in vitro to influenza viruses is predominantly directed against cross-reactive determinants on cells infected with serologically distinct type A influenza viruses.     

Follow-up study of type C influenza outbreak in a children's home

A follow-up study of type C influenza in a children's home was made where the first outbreak of type C influenza occurred in March, 1981. During the survey period of 2 years, 2 additional outbreaks occurred in April and October, 1982 and 4 cases of the secondary and 2 cases of the tertiary infections were serologically confirmed. All of the children exposed to the outbreaks, except 2 particular cases who were suffering from German measles, showed similar mild respiratory symptoms characterized by fever and long-lasting nasal discharge, irrespective of primary, secondary, and tertiary infections. No case of inapparent infection was observed. Incubation period was estimated to be not longer than 5 days and the period of virus shedding, to be longer than 22 days. Antibody response in the sera of patients to type C influenza virus was equally good after every infection, although it was not efficient to prevent the succeeding infection. Factors involved in the repeated infections of type C influenza were discussed.     

Clinical study to assess the immunogenicity and safety of a recombinant Pseudomonas aeruginosa OprF-OprI vaccine in burn patients

In a recent clinical trial we evaluated the safety and immunogenicity of a recombinant OprF-OprI vaccine consisting of the mature outer membrane protein I (OprI) and amino acids 190-342 of OprF of Pseudomonas aeruginosa in burn patients and compared the elicited antibodies with antibodies against tetanus as response to a simultaneous immunization given on the day of admission. Safety and immunogenicity of the vaccine had been tested before in healthy human volunteers as published in 1999. In this first clinical trial we immunized eight burn patients suffering from second or third degree burns involving between 35% and 55% of the body surface three times with 100 microg of the OprF-OprI vaccine. The vaccine was found to be very well tolerated. The patients did not show any serious side effects - and in particular no activation of the mediator cascade was observed. None of the subjects showed systemic P. aeruginosa infections during or after the treatment of their burns. The serological tests (ELISA) for detection of antibodies against P. aeruginosa and tetanus toxoid showed seroconversion for seven patients after inoculation. The data indicate that OprF-OprI can be a useful vaccine in the therapeutic management of burn injuries.     

Book Reviews

M ycotoxins (1974). Edited by I. F. H. Purchase.
C owan and S teel's M anual for the I dentification of M edical B acteria (1974). S. T. Cowan.
A C olour A tlas of M icrobiology (1975). R. J. Olds.
M embranes and their C ellular F unctions (1974). J. B. Finean, R. Coleman & R. H. Michell.
S ingle C ell P rotein (1974). Edited by P. Davis.
W riting S cientific P apers in E nglish (1975). Maeve O'Connor & F. P. Woodford.
M icrobiology Vol. I (1975). Edited by V. A. Sherin & L. S. Smirnova.