Effectiveness and Cost-Effectiveness of Inactivated Vaccine to Address COVID-19 Pandemic in China: Evidence From Randomized Control Trials and Real-World Studies.

Objective: This study aimed to determine the efficacy, effectiveness, and cost-effectiveness of inactivated COVID-19 vaccines (CoronaVac and BBIBP-CorV) in China using existing international clinical trials and real-world evidence. Methods: Through a search of PubMed, Embase, Web of Science, and CNKI, studies investigating the effectiveness of inactivated COVID-19 vaccines were identified, and a meta-analysis was undertaken to synthesize the vaccine efficacy and effectiveness data. Moreover, a decision-analytic model was developed to estimate the cost-effectiveness of inactivated vaccines for combating the COVID-19 pandemic in the Chinese context from a societal perspective. Results of the meta-analysis, along with cost data from official websites and works of literature were used to populate the model. Sensitivity analysis was performed to test the robustness of the model results. Results: A total of 24 studies were included in the meta-analysis. In comparison to no immunization, the effectiveness of inactivated vaccine against COVID-19 infection, hospitalization, ICU admission and death were 65.18% (95% CI 62.62, 67.75), 79.10% (95% CI 71.69, 86.51), 90.46% (95% CI 89.42, 91.50), and 86.69% (95% CI 85.68, 87.70); and the efficacy against COVID-19 infection and hospitalization were 70.56% (95% CI 57.87, 83.24) and 100% (95% CI 61.72, 100). Inactivated vaccine vaccination prevented more infections, hospitalizations, ICU admissions, and deaths with lower total costs, thus was cost-saving from a societal perspective in China. Base-case analysis results were robust in the one-way sensitivity analysis, and the percentage of ICU admission or death and direct medical cost ranked the top influential factors in our models. In the probabilistic sensitivity analysis, vaccination had a 100% probability of being cost-effective. Conclusion: Inactivated vaccine is effective in preventing COVID-19 infection, hospitalization, ICU admission and avoiding COVID-19 related death, and COVID-19 vaccination program is cost-saving from societal perspective in China.

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.

BACKGROUND: GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. METHODS: The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18-49 years; N = 120), children (3-17 years; N = 821), and infants (6-35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 µg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. RESULTS: The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). CONCLUSIONS: The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.

Vaccines for preventing influenza in healthy children.

BACKGROUND: The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. This is an update of a review published in 2011. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated because of their lack of influence on the review conclusions. OBJECTIVES: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 12), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1966 to 31 December 2016), Embase (1974 to 31 December 2016), WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017). SELECTION CRITERIA: Randomised controlled trials comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy children under 16 years. Previous versions of this review included 19 cohort and 11 case-control studies. We are no longer updating the searches for these study designs but have retained the observational studies for historical purposes. DATA COLLECTION AND ANALYSIS: Review authors independently assessed risk of bias and extracted data. We used GRADE to rate the certainty of evidence for the key outcomes of influenza, influenza-like illness (ILI), complications (hospitalisation, ear infection), and adverse events. Due to variation in control group risks for influenza and ILI, absolute effects are reported as the median control group risk, and numbers needed to vaccinate (NNVs) are reported accordingly. For other outcomes aggregate control group risks are used. MAIN RESULTS: We included 41 clinical trials (> 200,000 children). Most of the studies were conducted in children over the age of two and compared live attenuated or inactivated vaccines with placebo or no vaccine. Studies were conducted over single influenza seasons in the USA, Western Europe, Russia, and Bangladesh between 1984 and 2013. Restricting analyses to studies at low risk of bias showed that influenza and otitis media were the only outcomes where the impact of bias was negligible. Variability in study design and reporting impeded meta-analysis of harms outcomes.Live attenuated vaccinesCompared with placebo or do nothing, live attenuated influenza vaccines probably reduce the risk of influenza infection in children aged 3 to 16 years from 18% to 4% (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.41; 7718 children; moderate-certainty evidence), and they may reduce ILI by a smaller degree, from 17% to 12% (RR 0.69, 95% CI 0.60 to 0.80; 124,606 children; low-certainty evidence). Seven children would need to be vaccinated to prevent one case of influenza, and 20 children would need to be vaccinated to prevent one child experiencing an ILI. Acute otitis media is probably similar following vaccine or placebo during seasonal influenza, but this result comes from a single study with particularly high rates of acute otitis media (RR 0.98, 95% CI 0.95 to 1.01; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. Vaccinating children may lead to fewer parents taking time off work, although the CI includes no effect (RR 0.69, 95% CI 0.46 to 1.03; low-certainty evidence). Data on the most serious consequences of influenza complications leading to hospitalisation were not available. Data from four studies measuring fever following vaccination varied considerably, from 0.16% to 15% in children who had live vaccines, while in the placebo groups the proportions ranged from 0.71% to 22% (very low-certainty evidence). Data on nausea were not reported.Inactivated vaccinesCompared with placebo or no vaccination, inactivated vaccines reduce the risk of influenza in children aged 2 to 16 years from 30% to 11% (RR 0.36, 95% CI 0.28 to 0.48; 1628 children; high-certainty evidence), and they probably reduce ILI from 28% to 20% (RR 0.72, 95% CI 0.65 to 0.79; 19,044 children; moderate-certainty evidence). Five children would need to be vaccinated to prevent one case of influenza, and 12 children would need to be vaccinated to avoid one case of ILI. The risk of otitis media is probably similar between vaccinated children and unvaccinated children (31% versus 27%), although the CI does not exclude a meaningful increase in otitis media following vaccination (RR 1.15, 95% CI 0.95 to 1.40; 884 participants; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. We identified no data on parental working time lost, hospitalisation, fever, or nausea.We found limited evidence on secondary cases, requirement for treatment of lower respiratory tract disease, and drug prescriptions. One brand of monovalent pandemic vaccine was associated with a sudden loss of muscle tone triggered by the experience of an intense emotion (cataplexy) and a sleep disorder (narcolepsy) in children. Evidence of serious harms (such as febrile fits) was sparse. AUTHORS' CONCLUSIONS: In children aged between 3 and 16 years, live influenza vaccines probably reduce influenza (moderate-certainty evidence) and may reduce ILI (low-certainty evidence) over a single influenza season. In this population inactivated vaccines also reduce influenza (high-certainty evidence) and may reduce ILI (low-certainty evidence). For both vaccine types, the absolute reduction in influenza and ILI varied considerably across the study populations, making it difficult to predict how these findings translate to different settings. We found very few randomised controlled trials in children under two years of age. Adverse event data were not well described in the available studies. Standardised approaches to the definition, ascertainment, and reporting of adverse events are needed. Identification of all global cases of potential harms is beyond the scope of this review.

Effectiveness of seasonal influenza vaccine in Australia, 2015: An epidemiological, antigenic and phylogenetic assessment.

BACKGROUND: A record number of laboratory-confirmed influenza cases were notified in Australia in 2015, during which type A(H3) and type B Victoria and Yamagata lineages co-circulated. We estimated effectiveness of the 2015 inactivated seasonal influenza vaccine against specific virus lineages and clades. METHODS: Three sentinel general practitioner networks conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness in Australia. Data from the networks were pooled to estimate vaccine effectiveness (VE) for seasonal trivalent influenza vaccine in Australia in 2015 using the case test-negative study design. RESULTS: There were 2443 eligible patients included in the study, of which 857 (35%) were influenza-positive. Thirty-three and 19% of controls and cases respectively were reported as vaccinated. Adjusted VE against all influenza was 54% (95% CI: 42, 63). Antigenic characterisation data suggested good match between vaccine and circulating strains of A(H3); however VE for A(H3) was low at 44% (95% CI: 21, 60). Phylogenetic analysis indicated most circulating viruses were from clade 3C.2a, rather than the clade included in the vaccine (3C.3a). VE point estimates were higher against B/Yamagata lineage influenza (71%; 95% CI: 57, 80) than B/Victoria (42%, 95% CI: 13, 61), and in younger people. CONCLUSIONS: Overall seasonal vaccine was protective against influenza infection in Australia in 2015. Higher VE against the B/Yamagata lineage included in the trivalent vaccine suggests that more widespread use of quadrivalent vaccine could have improved overall effectiveness of influenza vaccine. Genetic characterisation suggested lower VE against A(H3) influenza was due to clade mismatch of vaccine and circulating viruses.

Influenza vaccination in HIV-infected individuals: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness and safety.

BACKGROUND: Influenza infection in HIV-infected individuals is associated with increased severity of illness. We performed a systematic review of the available evidence on efficacy, effectiveness and safety of seasonal influenza vaccination in HIV-infected individuals. DESIGN: Systematic review, meta-analysis and assessment of evidence quality. METHODS: Using a previous systematic review as starting point, we searched MEDLINE, EMBASE and Cochrane data base for studies on efficacy, effectiveness or safety of trivalent inactivated influenza vaccines (TIV) in HIV-infected individuals. Evidence quality was assessed for each outcome using the GRADE methodology. RESULTS: Three randomized-controlled trials and three cohort studies were identified, including a total of 1562 HIV-infected individuals. In adults, TIV prevented laboratory-confirmed influenza with a pooled efficacy of 85% (95% CI, 22-97%) (evidence quality: moderate), but no significant effects on other clinical outcomes were observed (evidence quality: moderate to low). One cohort study showed an effectiveness of 71% (95% CI, 44-85%) for prevention of laboratory-confirmed influenza, whereas no effect on influenza-like illness was found. However, risk of bias was high in all observational studies. In children aged 6-59 months, efficacy of TIV in preventing laboratory-confirmed influenza was 11% (95% CI, -30 to 54%) (evidence quality: moderate). Regarding other endpoints, no statistically significant effects were reported (evidence quality: moderate to low). No severe adverse events following influenza vaccination were observed in these studies. CONCLUSION: This systematic review indicates that TIV is effective in preventing influenza infection in HIV-infected adults but not in young children. For both age-groups, only limited evidence exists for other outcomes, indicating a need for further studies.

Cost-effectiveness analysis of universal influenza vaccination with quadrivalent inactivated vaccine in the United States.

To address influenza B lineage mismatch and co-circulation, several quadrivalent inactivated influenza vaccines (IIV4s) containing two type A strains and both type B lineages have recently been approved in the United States. Currently available trivalent inactivated vaccines (IIV3s) or trivalent live attenuated influenza vaccines (LAIV3s) comprise two influenza A strains and one of the two influenza B lineages that have co-circulated in the United States since 2001. The objective of this analysis was to evaluate the cost-effectiveness of a policy of universal vaccination with IIV4 vs. IIV3/LAIV3 during 1 year in the United States. On average per influenza season, IIV4 was predicted to result in 30,251 fewer influenza cases, 3512 fewer hospitalizations, 722 fewer deaths, 4812 fewer life-years lost, and 3596 fewer quality-adjusted life-years (QALYs) lost vs. IIV3/LAIV3. Using the Fluarix Quadrivalent(TM) (GlaxoSmithKline) prices and the weighted average IIV3/LAIV3 prices, the model predicts that the vaccination program costs would increase by $452.2 million, while direct medical and indirect costs would decrease by $111.6 million and $218.7 million, respectively, with IIV4. The incremental cost-effectiveness ratio (ICER) comparing IIV4 to IIV3/LAIV3 is predicted to be $90,301/QALY gained. Deterministic sensitivity analyses found that influenza B vaccine-matched and mismatched efficacies among adults aged ≥65 years had the greatest impact on the ICER. Probabilistic sensitivity analysis showed that the cost per QALY remained below $100,000 for 61% of iterations. In conclusion, vaccination with IIV4 in the US is predicted to reduce morbidity and mortality. This strategy is also predicted to be cost-effective vs. IIV3/LAIV3 at conventional willingness-to-pay thresholds.

Vaccines for preventing influenza in healthy children.

BACKGROUND: The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children, assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness (ILI)) and document adverse events associated with influenza vaccines. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) which includes the Acute Respiratory Infections Group's Specialised Register, OLD MEDLINE (1950 to 1965), MEDLINE (1966 to November 2011), EMBASE (1974 to November 2011), Biological Abstracts (1969 to September 2007), and Science Citation Index (1974 to September 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years of age. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included 75 studies with about 300,000 observations. We included 17 RCTs, 19 cohort studies and 11 case-control studies in the analysis of vaccine efficacy and effectiveness. Evidence from RCTs shows that six children under the age of six need to be vaccinated with live attenuated vaccine to prevent one case of influenza (infection and symptoms). We could find no usable data for those aged two years or younger.Inactivated vaccines in children aged two years or younger are not significantly more efficacious than placebo. Twenty-eight children over the age of six need to be vaccinated to prevent one case of influenza (infection and symptoms). Eight need to be vaccinated to prevent one case of influenza-like-illness (ILI). We could find no evidence of effect on secondary cases, lower respiratory tract disease, drug prescriptions, otitis media and its consequences and socioeconomic impact. We found weak single-study evidence of effect on school absenteeism by children and caring parents from work. Variability in study design and presentation of data was such that a meta-analysis of safety outcome data was not feasible. Extensive evidence of reporting bias of safety outcomes from trials of live attenuated influenza vaccines (LAIVs) impeded meaningful analysis. One specific brand of monovalent pandemic vaccine is associated with cataplexy and narcolepsy in children and there is sparse evidence of serious harms (such as febrile convulsions) in specific situations. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in preventing cases of influenza in children older than two years of age, but little evidence is available for children younger than two years of age. There was a difference between vaccine efficacy and effectiveness, partly due to differing datasets, settings and viral circulation patterns. No safety comparisons could be carried out, emphasising the need for standardisation of methods and presentation of vaccine safety data in future studies. In specific cases, influenza vaccines were associated with serious harms such as narcolepsy and febrile convulsions. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months of age in the USA, Canada, parts of Europe and Australia. If immunisation in children is to be recommended as a public health policy, large-scale studies assessing important outcomes, and directly comparing vaccine types are urgently required. The degree of scrutiny needed to identify all global cases of potential harms is beyond the resources of this review. This review includes trials funded by industry. An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry-funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favourable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in the light of this finding.

A two year BTV-8 vaccination follow up: molecular diagnostics and assessment of humoral and cellular immune reactions.

The compulsory vaccination campaign against Bluetongue virus serotype eight (BTV-8) in Germany was exercised in the state of Bavaria using three commercial monovalent inactivated vaccines given provisional marketing authorisation for emergency use. In eleven Bavarian farms representing a cross sectional area of the state the immune reactions of sheep and cattle were followed over a two year period (2008-2009) using cELISA, a serum neutralisation test (SNT) and interferon gamma (IFN-γ) ELISPOT. For molecular diagnostics of BTV genome presence two recommended real time quantitative RT-PCR protocols were applied. The recommended vaccination scheme led to low or even undetectable antibody titers (ELISA) in serum samples of both cattle and sheep. A fourfold increase of the vaccine dose in cattle, however, induced higher ELISA titers and virus neutralising antibodies. Accordingly, repeated vaccination in sheep caused an increase in ELISA-antibody titers. BTV-8 neutralising antibodies occurred in most animals only after multiple vaccinations in the second year of the campaign. The secretion of interferon gamma (IFN-γ) in ELISPOT after in vitro re-stimulation of PBMC of BTV-8 vaccinated animals with BTV was evaluated in the field for the first time. Sera of BTV-8 infected or vaccinated animals neutralising BTV-8 could also neutralise an Italian BTV serotype 1 cell culture adapted strain and PBMC of such animals secreted IFN-γ when stimulated with BTV-1.

Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding.

The killed oral cholera vaccine Dukoral is recommended for adults and only children over 2 years of age, although cholera is seen frequently in younger children and there is an urgent need for a vaccine for them. Since decreased immunogenicity of oral vaccines in children in developing countries is a critical problem, we tested interventions to enhance responses to Dukoral. We evaluated the effect on the immune responses by temporarily withholding breast-feeding or by giving zinc supplementation. Two doses of Dukoral consisting of killed cholera vibrios and cholera B subunit were given to 6-18 months old Bangladeshi children (n=340) and safety and immunogenicity studied. Our results showed that two doses of the vaccine were safe and induced antibacterial (vibriocidal) antibody responses in 57% and antitoxin responses in 85% of the children. Immune responses were comparable after intake of one and two doses. Temporary withholding breast-feeding for 3 h before immunization or supplementation with 20 mg of zinc per day for 42 days resulted in increased magnitude of vibriocidal antibodies (77% and 79% responders, respectively). Administration of vaccines without buffer or in water did not result in reduction of vibriocidal responses. This study demonstrates that the vaccine is safe and immunogenic in children under 2 years of age and that simple interventions can enhance immune responses in young children.

Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States.

BACKGROUND: The US Advisory Committee on Immunization Practices (ACIP) recently expanded the influenza vaccine recommendation to include children 24-59 months of age. In a large head-to-head randomized controlled trial, live attenuated influenza vaccine, trivalent (LAIV) demonstrated a 54% relative reduction in culture-confirmed influenza illness compared with trivalent inactivated influenza vaccine (TIV) among children aged 24-59 months. OBJECTIVE: To evaluate the relative cost and benefit between two influenza vaccines (LAIV and TIV) for healthy children 24-59 months of age. METHODS: Using patient-level data from the clinical trial supplemented with cost data from published literature, we modeled the cost-effectiveness of these two vaccines. Effectiveness was measured in quality-adjusted life years (QALY) and cases of influenza avoided. The analysis used the societal perspective. RESULTS: Due to its higher acquisition cost, LAIV increased vaccination costs by USD7.72 per child compared with TIV. However, compared with TIV, LAIV reduced the number of influenza illness cases and lowered the subsequent healthcare use of children and productivity losses of parents. The estimated offsets in direct and indirect costs saved USD15.80 and USD37.72 per vaccinated child, respectively. LAIV had a net total cost savings of USD45.80 per child relative to TIV. One-way and probabilistic sensitivity analyses indicated that the model was robust across a wide range of relative vaccine efficacy and cost estimates. CONCLUSIONS: Due to its increased relative vaccine efficacy over TIV, LAIV reduced the burden of influenza and lowered both direct health care and societal costs among children 24-59 months of age.

Evolution, benefits, and shortcomings of vaccine management.

BACKGROUND: The reduction of childhood mortality by vaccines has been one of the greatest public health successes of the past century. However, many targets for immunization remain uncontrolled, and new or improved vaccines are emerging to meet these challenges. OBJECTIVE: To review the evolution of vaccination and take an objective look at current vaccine development technologies, thereby framing the discussion of vaccine management. SUMMARY: The genesis of vaccinology is generally considered to have been a direct result of the observation that persons who had contracted smallpox rarely developed a second case. From this observation, the concept of variolation was born, which involved the inoculation of uninfected individuals using material collected from smallpox lesions with the goal of inducing immunity to future infection. The use of attenuated, live virus to induce immunity was the next step in the evolution of vaccinology, followed by inactivation of the virus when diseases caused by organisms not amenable to attenuation were targeted. More recently, a variety of adjuvant strategies have been developed to improve the immunogenicity of inactivated vaccines, and genetic engineering has been employed to increase the safety, reduce the reactogenicity, and improve the immunogenicity of different vaccines. CONCLUSION: Clinical (efficacy and safety) and economic (cost and profit) considerations are competing priorities that need to be reconciled within a discussion encompassing the government, the public, the pharmaceutical industry, third-party payers, and private individuals or companies who administer these vaccines.

Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients.

Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other "at risk" groups to reduce morbidity, save lives, and reduce health care costs.

Assessment of effectiveness of Vaxigrip.

In order to assess the effectiveness of Vaxigrip in 1996-1997, we chose 1356 people in the Chinese Army, who had not recently had influenza and who were divided into an injection group and a control group. The injection group consisted of 80 children aged 3-6 years, 363 adults aged 18-59 years and 235 people over 60 years of age. The control group consisted of 88 children aged 3-6, 372 adults aged 18-59 and 218 people over 60. They were observed from the 21st day to the 6th month after Vaxigrip administration. Each person was requested to report having a body temperature over 38.5 degrees C, headache, myalgia or arthalgia, cough, pharyngodynia or nasal obstruction. Fever due to other causes was not included in the influenza symptoms. We counted the symptoms of influenza and common cold only once during the observation period. Our final finding was that the incidence rates of the influenza and common cold symptoms were reduced by 84.8% in children, 74.0% in adults and 68.6% in elderly people. In comparison with the control group, the incidence rate of influenza-like symptoms was reduced by 71.1% in the injection group, and the incidence rate of common cold symptoms in the injection group was lower than that in the control group. There was no large difference by age. The incidence rate of symptoms of upper respiratory tract infection in the injection group was 47.5% lower than that in the control group. Our findings are basically the same as those in other countries.

Consideraciones sobre el uso programático de vacuna inactivada contra la hepatitis A en Chile / Considerations about the programatic use of inactivated hepatitis A vaccine in Chile

La epidemiología de la hepatitis A está cambiando en Chile como consecuencia del desarrollo económico y cultural. Estudios recientes de seroprevalencia efectuados en Santiago permiten afirmar que actualmente coexisten en el país poblaciones que adquieren la infección tempranamente en la vida y otras que permanecen susceptibles hasta la adultez. Dos vacunas elaboradas con virus inactivado, con alta eficacia y seguridad están licenciadas en el país y se comercializan libremente. La inexistencia de registros nacionales acabados sobre la incidencia de la enfermedad por edad y regiones geográficas dificulta efectuar estudios de costo/beneficio para considerar la introducción de la vacuna anti hepatitis A al Programa Ampliado de Inmunizaciones (PAI). Una acabada vigilancia de la morbimortalidad por hepatitis A y estudios de seroprevalencia representativos de todo el país permitirán orientar la decisión de las autoridades de salud hacia la aplicación programática de esta vacuna en relación con otras prioridades en el área. Es necesario evaluar la seroconversión conferida por las vacunas inactivadas en el primer año de vida a hijos de madres seropositivas en la perspectiva de combinar esta vacuna con las utilizadas en el PAI. Por otra parte, el impacto de la inmunización artificial temprana de una población altamente expuesta a la infección con una vacuna cuyo efecto protector es de duración aún desconocida, es un aspecto a vigilar en caso de iniciarse este programa. Se hace énfasis en la indicación de inmunización selectiva de grupos de mayor riesgo de infectarse (politransfundidos), homosexuales masculinos, drogadictos intravenosos), desarrollar enfermedad severa (portadores de hepatopatías crónicas) o impacto epidemiológico (manipuladores de alimentos)