Evaluation of the efficacy of split-product trivalent A(H1N1), A(H3N2), and B influenza vaccines: protective efficacy

A total of 1,995 primary school children (1,464 vaccinees and 531 non-vaccinees) were studied to evaluate the protective efficacy of Tween-ether split trivalent A(H1N1), A(H3N2), and B influenza vaccines by comparison of the incidence of confirmed infection in two groups during 1980 to 1984. During the study period, epidemics caused by antigenically different influenza viruses, that is A(H1N1) epidemics in 1981 and 1984, a B epidemic in 1982 and an A(H3N2) epidemic in 1983, were experienced, and at the same time strains changed by antigenic drift were frequently isolated. In these epidemics, 61% to 87% of the children reported respiratory illnesses and 18% to 48% of the illnesses were influenza confirmed by seroconversion. Throughout these four epidemics, the incidence of confirmed infection among the vaccinees (7.8% to 33.8%) was 6.5% to 34.8% lower than that among the nonvaccinees (35.4% to 51.6%), demonstrating that the vaccine was effective (X2 = 76.34, P less than 0.001). However, this effectiveness was not seen in an epidemic in one of the entrant schools in 1984, possibly caused by a strain with intense antigenic drift. On the basis of data on incidence of various symptoms, duration of fever and the number of days of absence from class, it was considered that clinical symptoms in the vaccinees were milder than those in the nonvaccinees. When the titers of hemagglutination-inhibiting (HAI) antibody against the vaccine strains were measured, the protective level of HAI antibody giving less than or equal to 50% incidence of infection was 1:64, but it increased to 1:256 in the 1984 epidemic, reflecting the high rate of isolates with intense antigenic drift.     

Age Distribution of Influenza Like Illness Cases during Post-Pandemic A(H3N2): Comparison with the Twelve Previous Seasons,in France

In France, the 2011–2012 influenza epidemic was characterized by the circulation of antigenically drifted influenza A(H3N2) viruses and by an increased disease severity and mortality among the elderly, with respect to the A(H1N1)pdm09 pandemic and post-pandemic outbreaks. Whether the epidemiology of influenza in France differed between the 2011–2012 epidemic and the previous outbreaks is unclear. Here, we analyse the age distribution of influenza like illness (ILI) cases attended in general practice during the 2011–2012 epidemic, and compare it with that of the twelve previous epidemic seasons. Influenza like illness data were obtained through a nationwide surveillance system based on sentinel general practitioners. Vaccine effectiveness was also estimated. The estimated number of ILI cases attended in general practice during the 2011–2012 was lower than that of the past twelve epidemics. The age distribution was characteristic of previous A(H3N2)-dominated outbreaks: school-age children were relatively spared compared to epidemics (co-)dominated by A(H1N1) and/or B viruses (including the 2009 pandemic and post-pandemic outbreaks), while the proportion of adults over 30 year-old was higher. The estimated vaccine effectiveness (54%, 95% CI (48, 60)) was in the lower range for A(H3N2) epidemics. In conclusion, the age distribution of ILI cases attended in general practice seems to be not different between the A(H3N2) pre-pandemic and post-pandemic epidemics. Future researches including a more important number of ILI epidemics and confirmed virological data of influenza and other respiratory pathogens are necessary to confirm these results.     

Influenza activity in Czechoslovakia and the USSR, 1980-1985

Between 1980 and 1985, Czechoslovakia had experienced 4 and the USSR 3 major influenza outbreaks. Of the 3 epidemic outbreaks in the USSR, 2 were associated with influenza B virus (in the 1980/81 and 1983/84 seasons) and 1 with influenza A virus of the H3N2 subtype. In the USSR, influenza A (H1N1) virus never predominated as a cause of epidemic during the 5 years period. In Czechoslovakia, 2 epidemics (in the 1980/81 and 1983/84 seasons) were due to influenza A (H1N1) virus. The epidemic in the 1981/82 season had two waves of unequal heights and a mixed type B and subtype A (H3N2) etiology; a two-wave epidemic associated with isolates of influenza A (H1N1) and influenza B viruses was also recorded in the 1983/84 season. The influenza A (H3N2) epidemic in 1983 was of explosive character. All influenza viruses circulating in the two countries between 1980 and 1985 were of the same antigenic profile, but were isolated from the epidemics that occurred in different influenza seasons. The virological surveillance revealed strains of virus closely related to drift variants detected from outbreaks in 1977-1979 and the new variants A/Chile 1/83, A/Philippines 2/82, A/Caen 1/84 and B/USSR 100/83.     

Assessment of the effectiveness of inactivated influenza vaccines for adults

In 9 controlled epidemiological observations (1977-1984) the effectiveness of modern Soviet whole-virion vaccines was studied in organized groups of adults and at industrial enterprises. During the epidemic outbreaks of influenza of different etiology and intensity morbidity rate in influenza and acute respiratory diseases was shown to decrease 1.1-2.2 times among the vaccinees, depending on the correspondence of epidemic and vaccine influenza strains. The absence of influenza virus B in inactivated influenza vaccines was the reason for their low effectiveness during influenza outbreaks of mixed etiology B + A (H1N1).     

Properties of current influenza A (H1N1) virus strains and the characteristics of the epidemics they induce

Three epidemics of influenza A (H1N1) occurring in 1977, 1979 and 1981 were studied. These epidemics were found to be gradually dying down, which was manifested by progressively decreasing morbidity rate, the frequency and intensity of seroconversions, as well as by a decrease in the duration of the epidemic period. Changes in the biological properties of influenza A (H1N1) virus were accompanied by changes in its antigenic properties. The drift of neuraminidase in the influenza A (H1N1) virus of 1981 towards increased relationship with neuraminidase in the virus of 1952 was observed, while hemagglutinin in the strains of each of these two groups retained its individual character.     

Etiology of influenza according to the data of serological diagnostics in hospital patients in St. Petersburg at the period of 1968 - 2000

The specific features of the etiology of influenza in children and adults at the period of the simultaneous circulation of two subtypes of influenza virus A, according to the results in the hemagglutination-inhibition reaction in 261,490 influenza and ARD patients hospitalized in St. Petersburg in the course of 32 years, were analyzed. The results of serological diagnostics was shown to correspond to the data of the identification of influenza viruses in Russia and all over the world. At the period of epidemics diseases caused by the main infective agents of the epidemics were detected in 11.0% - 51.0% of cases and by concomitant infective agents, in 0.6% - 12.4% of cases. After the reappearance of influenza virus A(H1N1) in circulation higher frequency of mixed forms of infection and the presence of competition between the subtypes of influenza virus A was noted. In young children a decrease in differences in the proportion of influenza cases, caused by the main and concomitant infective agents, as well as between the detection of influenza in epidemic and in summer periods, was registered.     

Basic results of a committee trial of the new vaccine Grippovac SE-AZh

In the trial of the trivalent subunit influenza vaccine Grippovac CE-AK observations on children aged 3-6 years were made. The preparation showed insignificant reactogenicity and moderate antigenic potency. The trial established that at the period of the epidemic rise of influenza B morbidity the vaccine showed, according to the data of the clinical diagnosis of influenza, insignificant effectiveness, its index of effectiveness (IE) being 1.08; according to the data of the serological diagnosis of influenza, only the A (H1N1) component of the vaccine was found to have IE equal to 1.58.     

The clinico-epidemiological characteristics of the course of a mixed epidemic of influenza and respiratory syncytial infection in Novoshakhtinsk in the summer of 1986

In the summer of 1986 the epidemic, whose etiological agents were influenza viruses A (H1N1) and respiratory syncytial virus, was registered among the population of Novoshakhtinsk. In a number of mines 15.3-16.7% of the employees were affected. Influenza viruses A (H1N1) proved to be closely related in their antigenic and biological properties to viruses isolated in the USSR in March-June 1986, as well as to viruses A (H1N1), the etiological agents of the epidemic which developed in the USSR in October-December 1986.     

Surveillance for Seasonal Influenza Virus Prevalence in Hospitalized Children with Lower Respiratory Tract Infection in Guangzhou,China during the Post-Pandemic Era

Background

Influenza A(H1N1)pdm09, A(H3N2) and B viruses have co-circulated in the human population since the swine-origin human H1N1 pandemic in 2009. While infections of these subtypes generally cause mild illnesses, lower respiratory tract infection (LRTI) occurs in a portion of children and required hospitalization. The aim of our study was to estimate the prevalence of these three subtypes and compare the clinical manifestations in hospitalized children with LRTI in Guangzhou, China during the post-pandemic period.

Methods

Children hospitalized with LRTI from January 2010 to December 2012 were tested for influenza A/B virus infection from their throat swab specimens using real-time PCR and the clinical features of the positive cases were analyzed.

Results

Of 3637 hospitalized children, 216 (5.9%) were identified as influenza A or B positive. Infection of influenza virus peaked around March in Guangzhou each year from 2010 to 2012, and there were distinct epidemics of each subtype. Influenza A(H3N2) infection was more frequently detected than A(H1N1)pdm09 and B, overall. The mean age of children with influenza A virus (H1N1/H3N2) infection was younger than those with influenza B (34.4 months/32.5 months versus 45 months old; p<0.005). Co-infections of influenza A/ B with mycoplasma pneumoniae were found in 44/216 (20.3%) children.

Conclusions

This study contributes the understanding to the prevalence of seasonal influenza viruses in hospitalized children with LRTI in Guangzhou, China during the post pandemic period. High rate of mycoplasma pneumoniae co-infection with influenza viruses might contribute to severe disease in the hospitalized children.     

Influenza A/H1N1 2009 Pandemic and Respiratory Virus Infections,Beijing, 2009–2010

To determine the role of the pandemic influenza A/H1N1 2009 (A/H1N1 2009pdm) in acute respiratory tract infections (ARTIs) and its impact on the epidemic of seasonal influenza viruses and other common respiratory viruses, nasal and throat swabs taken from 7,776 patients with suspected viral ARTIs from 2006 through 2010 in Beijing, China were screened by real-time PCR for influenza virus typing and subtyping and by multiplex or single PCR tests for other common respiratory viruses. We observed a distinctive dual peak pattern of influenza epidemic during the A/H1N1 2009pdm in Beijing, China, which was formed by the A/H1N1 2009pdm, and a subsequent influenza B epidemic in year 2009/2010. Our analysis also shows a small peak formed by a seasonal H3N2 epidemic prior to the A/H1N1 2009pdm peak. Parallel detection of multiple respiratory viruses shows that the epidemic of common respiratory viruses, except human rhinovirus, was delayed during the pandemic of the A/H1N1 2009pdm. The H1N1 2009pdm mainly caused upper respiratory tract infections in the sampled patients; patients infected with H1N1 2009pdm had a higher percentage of cough than those infected with seasonal influenza or other respiratory viruses. Our findings indicate that A/H1N1 2009pdm and other respiratory viruses except human rhinovirus could interfere with each other during their transmission between human beings. Understanding the mechanisms and effects of such interference is needed for effective control of future influenza epidemics.     

Epidemiological analysis of acute respiratory diseases (ARD) of viral etiology in the Czech Socialist Republic (CSR] and German Democratic Republic (GDR) over the period 1979 to 1984

An analysis is made of the ARD reported in CSR and the GDR over the period July 1st, 1979 to June 30th, 1984. During that time, there were 27,810,000 cases reported in CSR in the framework of ARD epidemiological surveillance, representing 2.67 cases per one inhabitant, whereas in the GDR, the total number of reported ARD was 28,900,000 yielding 1.73 cases per person. However, the GDR reported higher morbidity per one child of preschool age. The authors believe that the differences in the reported incidence of ARD between the two countries are due to differences in the reporting systems and medical officers' activity during an epidemic and in the interim period. Approximately one third of ARD reported annually in the two countries falls to the period of influenza epidemics. The authors also analyze the etiology of the influenza epidemics which affected the two countries in 1980, 1981, 1982, 1983 and 1984. In most seasons, the causative agents and morbidity excesses were different in the two countries. The drift variant B/USSR/100/83, which caused a major epidemy in CSR in 1984, has not to date been implicated in the DGR in the etiology of ARD. The cyclic epidemic due to Mycoplasma pneumoniae occurred in the GDR already in 1979-80, while CSR experienced it a year later. There was a temporal and territorial correlation between the course of A(H1N1) influenza epidemic in the two countries in 1984.     

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized.     

The laboratory epidemiological study of the joint circulation of the influenza virus A subtypes A/H1N1/ and A/H3N2/ in Bulgaria]

The National Influenza Center of Bulgaria made the epidemiological analysis of the spread of influenza virus, type A, for the period of 11 years on the basis of mass laboratory investigations. Subtype A (H1N1) was found to be the main factor of epidemics in 1978 and 1982, while the epidemics of 1980, 1983, 1985, 1986, 1987 and 1988 were mainly caused by subtype A (H3N2). The data of laboratory and epidemiological studies indicated that after 20-year absence influenza virus A, subtype A (H1N1), was found again to circulate among the population of Bulgaria, and in 1978-1988 circulated simultaneously with the previous subtype A (H3N2). The simultaneous circulation of two subtypes of influenza virus was of great importance for the frequency, spread and duration of influenza epidemics.     

Results of virological and serological studies of three influenza A Hong-Kong epidemics in Leningrad.

An analysis of morbidity of the population in the course of 3 influenza A/Hong-Kong epidemics showed a pronounced decrease in influenza affection of adult population in the last epidemic in 1971--1972. Comparative studies of the diagnostic value of CFR and HIT demonstrated identical sensitivity of CFR as a method of influenza diagnostics in both the epidemic and interepidemic periods. HIT was suitable for the detection of influenza only in the epidemic period. In the interepidemic period, the percentage of influenza infection diagnosed by means of HIT ammounted to only 23--24 of all serologically confirmed cases of influenza. The highest percentage of virus isolation was observed when material from patients with serologically confirmed influenza was used. All strains of influenza A virus isolated in 1969 and 1970 were similar in their sensitivity to inhibitors of animal sera. During the last influenza epidemic, 2 of the 136 isolated strains were found to be resistant to gamma inhibitors and highly sensitive to the inhibitors showed their close relationship to gamma inhibitors. Antigenic analysis of the influenza A strains isolated during the 3 influenza epidemics revealed changes in the antigenic structure of the agents of the influenza epidemic in Leningrad in comparison with the standard strain A/Hong-Kong/I/68 (H3N2).     

Immunogenicity and the protective effectiveness of the subunit trivalent influenza vaccine Grippovac

In the process of the immunological approbation of several experimental batches of the triyalent subunit influenza vaccine Grippovac, the pronounced immunogenicity of the antigens of all strains contained in the vaccine was established; most of the vaccinees were found to retain sufficiently high antibody titers for a year, and the essential total increase of antibody titers was found to occur after a single booster immunization. The serological checking of the diagnosed cases of influenza among immunized and nonimmunized children, carried out in two boarding schools during the influenza epidemic in the winter of 1984-1985 provided the proofs of the high effectiveness of Grippovac in preventing viral influenza, types A and B: the decrease of influenza morbidity among the immunized children reached 79,5-67,2-66,5% and the total morbidity rate in influenza in these two boarding scholls dropped, on the average, 3,0-3,5 times.     

Epidemiological effectiveness of an inactivated three-component flu vaccine with an increased concentration of hemagglutinin in the inoculation dose]

The work presents the results of the evaluation of mass immunization of working adults with inactivated trivalent influenza vaccine under the conditions of an epidemic caused by influenza viruses A (H1N1), A (H3N2) and B. This immunization produced no effect on influenza morbidity in the groups of vaccinees in comparison with those of nonvaccinated persons. The index of effectiveness was 1.0 and less. The ineffectiveness of mass immunization was due to a high level of natural immunity to influenza and the extensive use of influenza vaccine in past years.     

The herald waves of influenza virus infections detected in Sendai and Yamagata cities in 1985-1990

The community surveillance of respiratory virus infections performed during 1985-1987 in Sendai and 1988-1990 in Yamagata has identified a total of five herald waves of influenza virus infections: A/H3N2 virus infections in 1985 and 1989, A/H1N1 virus infections in 1986 and 1988, and type B virus infections in 1989. To investigate the antigenic and genetic relationships between the herald wave and epidemic strains, influenza A/H1N1 viruses isolated during the 1986 and 1988 herald waves were compared with those isolated during the 1986-1987 and 1988-1989 epidemic seasons, respectively, utilizing hemagglutination inhibition tests with anti-hemagglutinin monoclonal antibodies and oligonucleotide mapping of total viral RNAs. The results showed that multiple variants differing in antigenic and genetic properties were cocirculating during the 1986 herald wave as well as during each of the two epidemics (only one strain was isolated in the 1988 herald wave). It was also observed that viruses which had the antigenic and/or genetic characteristics closely similar to those of the viruses circulating in the 1986 and 1988 herald waves, were isolated during the winters of 1986-1987 and 1988-1989, respectively.     

The results of state trials of inactivated influenza vaccines for children

Controlled epidemiological surveillance covering the total number of 13,355 schoolchildren aged 11-14 years and adolescents was carried out with a view to compare the efficacies of inactivated influenza vaccines. The children were immunized intradermally in a single injection with inactivated influenza vaccines containing A (H3N2) and A (H1N1) hemagglutinins, 3.5 micrograms per 0.2 ml of the preparation each. The studies demonstrated the safety and low reactogenicity of these vaccines, as well as their high antigenic potency. In 1984 during mixed influenza B + A (H1N1) epidemic the preparations produced a pronounced prophylactic effect: the efficacy indices were 1.6-1.9 (p less than 0.001). The results obtained in these studies made it possible to recommend two inactivated influenza vaccines (chromatographic and centrifugal) for practical medicine with the aim of protecting children aged 11 years and over from influenza.     

Morbidity and mortality in acute viral hepatitides in a hyperendemic region. The role of viral hepatitis E

Official annual statistical data on morbidity in acute viral hepatitides (AVH), including the number of lethal cases, for 1985-1995 were analyzed. Mortality rates per 100,000 of the population at the period of 11 years were calculated for different age groups, sex and the place of residence. 396 and 99 patients were examined for the presence of serological markers of hepatitides A, B and E, respectively, at the periods of epidemic rises in morbidity and satisfactory epidemic situation. In the course of 11 years AVH caused the death of 22,405 persons. In 1985-1987 the average mortality level (ML) reached 12.3-17.8 per 100,000 of the population (with morbidity being 1,200-1,400 and was essentially higher among the rural population in comparison with the urban population. During these years the highest ML, was registered among children aged 0-2 years (190-50 per 100,000) and, among adults, mainly among women aged 20-29 years (21.4-19.6 per 100,000). During the years when the epidemic of AVH was absent, ML among these groups was essentially lower: 40-20 among children aged 0-2 years and 4-5 among women aged 20-29 years. In 1987 in the Fergana Valley hepatitis E was detected in 72.2% of all examined patients, and in the southern areas of the country in 68.7%. A sharp rise on mortality among women of the productive age at the period of the epidemic rise of AVH morbidity in the endemic region indicated that this epidemic was linked with hepatitis E. High ML among young children may be indicative of a highly unfavorable course of hepatitis E in the group of infants, which had never been registered before. This newly established regularity may be used for the retrospective diagnostics of the outbreak of hepatitis E.