Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Association of Diabetes and Tuberculosis Disease among US-Bound Adult Refugees, 2009-2014.

Diabetes is associated with an increased risk for active tuberculosis (TB) disease. We conducted a case-control study and found a significant association between diabetes and TB disease among US-bound refugees. These findings underscore the value of collaborative management of both diseases.

Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia.

BACKGROUND: Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program. METHODS: An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) "No Program," 2) U.S. "Domestic Screening and Treatment," 3) "Overseas Albendazole and Ivermectin" presumptive treatment, and 4) "Overseas Albendazole and Domestic Screening for Strongyloides". Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs). RESULTS: The "No Program" option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The "Overseas Albendazole and Ivermectin" option ($418,824) is less expensive than "Domestic Screening and Treatment" ($3,832,572) or "Overseas Albendazole and Domestic Screening for Strongyloides" ($2,182,483). According to the model outcomes, the most effective treatment option is "Overseas Albendazole and Ivermectin," which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to "No Program". DISCUSSION: Overseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic screening and treatment programs. The addition of ivermectin to albendazole reduces the prevalence of chronic strongyloidiasis and the probability of rare, but potentially fatal, disseminated strongyloidiasis.

Diabetes Among United States-Bound Adult Refugees, 2009-2014.

We reported diabetes prevalence among all US-bound adult refugees and assessed factors associated with disease. We analyzed overseas medical evaluations of US-bound refugees from 2009 through 2014 by using CDC's Electronic Disease Notification System. We identified refugees with diabetes by searching for diabetes-related keywords and medications in examination forms with text-parsing techniques. Age-adjusted prevalence rates were reported and factors associated with diabetes were assessed by using logistic regression. Of 248,850 refugees aged ≥18 years examined over 5 years, 5767 (2.3 %) had diabetes. Iraqis had the highest crude (5.1 %) and age-adjusted (8.9 %) prevalence of disease. Higher age group and body mass index were associated with diabetes in all regions. Diabetes prevalence varied by refugee nationality. Although the absolute rates were lower than rates in the United States, the prevalence is still concerning given the younger age of the population and their need for health services upon resettlement.

Latent Tuberculosis Infection Among Immigrant and Refugee Children Arriving in the United States: 2010.

Immigrants and refugees age 2-14 years entering the United States from countries with estimated tuberculosis (TB) incidence rate ≥20 per 100,000 population are screened for TB. Children with TB disease are treated before US arrival. Children with positive tuberculin skin tests (TST), but negative TB evaluation during their pre-immigration examination, are classified with latent TB infection (LTBI) and are recommended for re-evaluation post-arrival. We examined post-immigration TB evaluation and therapy for children arriving with LTBI. We reviewed medical exam data from immigrant children with medical conditions and all refugee children arriving during 2010. Medical examination data were available for 67,334 children. Of these, 8231 (12 %) had LTBI pre-immigration; 5749 (70 %) were re-evaluated for TB post-immigration, and 64 % were retested by TST or IGRA. The pre-immigration LTBI diagnosis was changed for 38 % when retested by TST and for 71 % retested by IGRA. Estimated LTBI therapy initiation and completion rates were 68 and 12 %. In this population, testing with IGRA may limit the number of children targeted for therapy. Increased pre-immigration TB screening with post-immigration follow-up evaluation leading to completion of LTBI therapy should be encouraged to prevent TB reactivation.

A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program.

BACKGROUND: This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. METHODS: Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. RESULTS: For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). CONCLUSIONS: Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases in the United States was not considered in the model.

Cost-Effectiveness of Screening and Treating Foreign-Born Students for Tuberculosis before Entering the United States.

INTRODUCTION: The Centers for Disease Control and Prevention is considering implementation of overseas medical screening of student-visa applicants to reduce the numbers of active tuberculosis cases entering the United States. OBJECTIVE: To evaluate the costs, cases averted, and cost-effectiveness of screening for, and treating, tuberculosis in United States-bound students from countries with varying tuberculosis prevalence. METHODS: Costs and benefits were evaluated from two perspectives, combined and United States only. The combined perspective totaled overseas and United States costs and benefits from a societal perspective. The United States only perspective was a domestic measure of costs and benefits. A decision tree was developed to determine the cost-effectiveness of tuberculosis screening and treatment from the combined perspective. RESULTS: From the United States only perspective, overseas screening programs of Chinese and Indian students would prevent the importation of 157 tuberculosis cases annually, and result in $2.7 million in savings. From the combined perspective, screening programs for Chinese students would cost more than $2.8 million annually and screening programs for Indian students nearly $440,000 annually. From the combined perspective, the incremental cost for each tuberculosis case averted by screening Chinese and Indian students was $22,187 and $15,063, respectively. Implementing screening programs for German students would prevent no cases in most years, and would result in increased costs both overseas and in the United States. The domestic costs would occur because public health departments would need to follow up on students identified overseas as having an elevated risk of tuberculosis. CONCLUSIONS: Tuberculosis screening and treatment programs for students seeking long term visas to attend United States schools would reduce the number of tuberculosis cases imported. Implementing screening in high-incidence countries could save the United States millions of dollars annually; however there would be increased costs incurred overseas for students and their families.

Update: vitamin B12 deficiency among Bhutanese refugees resettling in the United States, 2012.

In 2008, clinicians performing routine medical examinations in the United States reported high rates of hematologic and neurologic disorders caused by vitamin B12 deficiency in resettled Bhutanese refugees. To confirm this finding, CDC screened Bhutanese refugees' serum samples for vitamin B12 levels and found vitamin B12 deficiency in 64% (n = 99) of samples obtained before departure and 27% (n = 64) of samples obtained after arrival in the United States. In response, CDC recommended that arriving Bhutanese refugees receive oral vitamin B12 supplements and nutrition advice. In 2012, based on anecdotal reports of decreasing rates of vitamin B12 deficiency in this population, CDC worked with select domestic refugee health programs to determine if the recommendations had reduced the vitamin B12 deficiency rate among Bhutanese refugees.

Measles outbreak associated with adopted children from China--Missouri, Minnesota, and Washington, July 2013.

On July 5, 2013, CDC was notified of two cases of laboratory-confirmed measles in recently adopted children from an orphanage in Henan Province, China. To find potentially exposed persons, CDC collaborated with state and local health departments, the children's adoption agency, and airlines that carried the adoptees. Two additional measles cases were identified, one in a family member of an adoptee and one in a third adopted child from China. To prevent further importation of measles, CDC worked with health officials in China, including "panel physicians" contracted by the U.S. Department of State to conduct the overseas medical examinations required for all immigrants and refugees bound for the United States. The following measures were recommended: 1) all adoptees examined at panel physician facilities should be screened for fever and rash illness, 2) measles immunity should be ensured among all adoptees from Henan Province who are scheduled for imminent departure to the United States, and 3) all children at the orphanage in Henan Province should be evaluated for measles. This report summarizes the results of the outbreak investigation and underscores the importance of timely routine vaccination for all international adoptees.

Disease surveillance among newly arriving refugees and immigrants--Electronic Disease Notification System, United States, 2009.

PROBLEM/CONDITION: Approximately 450,000 legal permanent immigrants and 75,000 refugees enter the United States annually after receiving required medical examinations by overseas panel physicians (physicians who follow the CDC medical screening guidelines provided to the U.S. Department of State). CDC has the regulatory responsibility for preventing the introduction, transmission, and spread of communicable diseases into the United States as well as for developing the guidelines, known as technical instructions, for the overseas medical examinations. Other conditions that are not infectious might preclude an immigrant or refugee from entering the United States and also are reported as part of the medical examination. After arrival in the United States, all refugees are recommended to obtain a medical assessment by a health-care provider or a health department within 30 days. In addition, immigrants with certain medical conditions such as noninfectious tuberculosis at the time of the original medical examination are recommended to be evaluated after arrival to ensure that appropriate prevention or treatment measures are instituted. Health departments need timely and accurate notifications of newly arriving immigrants, refugees, and persons with other visa types to facilitate these evaluations. Notifications for all newly arriving refugees (with or without medical conditions) and immigrants with medical conditions are provided by CDC's Electronic Disease Notification (EDN) system. This is the first report describing EDN. REPORTING PERIOD: This report summarizes notifications by the EDN system during January-December 2009. DESCRIPTION OF SYSTEM: The EDN system is a centralized electronic reporting system that collects health information on newly arriving refugees and immigrants with Class A and Class B medical conditions. Class A conditions render applicants inadmissible and require a waiver for entry; Class B conditions are admissible but might require treatment or follow-up. Information in the EDN system is used to notify state health departments in all 50 states and the District of Columbia about the arrival of these persons in the United States. RESULTS: In 2009, the EDN system notified U.S. state and local health departments of 104,954 newly arriving refugees and immigrants, of whom 78,899 (75.2%) were refugees (with or without medical conditions), 19,358 (18.4%) were immigrants with medical conditions, and 6,697 (6.4%) were persons with other visa types. Of the 78,899 refugees, 21,319 (27%) had a medical condition. The majority (93.4%) of immigrants with medical conditions had tuberculosis classifications (i.e., either had evidence of latent tuberculosis infection or chest radiograph findings interpreted by the overseas panel physician as consistent with tuberculosis). Of the 41,415 refugees and immigrants with Class A or Class B medical conditions, 405 (1%) had Class A conditions, and 40,994 (99%) had Class B conditions. The majority of refugees and immigrants with suspected Class B tuberculosis were born in the Philippines (41.3%), Mexico (12.1%), Burma (8.7%), Vietnam (7.8%), and the Dominican Republic (5.8%). The majority of refugee notifications were for persons born in Iraq (23.9%), Burma (18.9%), and Bhutan (15.1%). Approximately one third of the tuberculosis notifications were sent to health departments in California (20.5%), Texas (9.8%), and New York (6.3%), and the national reporting rate for tuberculosis follow-up was 75.4% within 30 days of arrival. INTERPRETATION: The findings in this report suggest that 1) overseas medical screening results in a low frequency (0.4%) of inadmissible medical conditions in the United States, 2) the EDN system provides more direct notifications to health departments than the previous paper-based system about newly arriving immigrants and refugees who need medical follow-up, and 3) approximately 75% of follow-up occurs among persons with suspected tuberculosis who are reported to EDN by states receiving newly arriving refugees and immigrants. PUBLIC HEALTH ACTIONS: The data in this report can be used to help state and local health departments provide prompt and effective follow-up, evaluation, and treatment to newly arriving immigrants and refugees. Timely follow-up might prevent additional spread of tuberculosis or other communicable diseases of public health significance into their communities. In addition, information from the EDN system allows health departments to use their resources as effectively as possible by providing clinical information that identifies the refugees and immigrants who should be prioritized for evaluation and treatment.

Influenza activity in Cambodia during 2006-2008.

BACKGROUND: There is little information about influenza disease among the Cambodian population. To better understand the dynamics of influenza in Cambodia, the Cambodian National Influenza Center (NIC) was established in August 2006. To continuously monitor influenza activity, a hospital based sentinel surveillance system for ILI (influenza like illness) with a weekly reporting and sampling scheme was established in five sites in 2006. In addition, hospital based surveillance of acute lower respiratory infection (ALRI) cases was established in 2 sites. METHODS: The sentinel sites collect weekly epidemiological data on ILI patients fulfilling the case definition, and take naso-pharyngeal specimens from a defined number of cases per week. The samples are tested in the Virology Unit at the Institut Pasteur in Phnom Penh. From each sample viral RNA was extracted and amplified by a multiplex RT-PCR detecting simultaneously influenza A and influenza B virus. Influenza A viruses were then subtyped and analyzed by hemagglutination inhibition assay. Samples collected by the ALRI system were tested with the same approach. RESULTS: From 2006 to 2008, influenza circulation was observed mainly from June to December, with a clear seasonal peak in October shown in the data from 2008. CONCLUSION: Influenza activity in Cambodia occurred during the rainy season, from June to December, and ended before the cool season (extending usually from December to February). Although Cambodia is a tropical country geographically located in the northern hemisphere, influenza activity has a southern hemisphere transmission pattern. Together with the antigenic analysis of the circulating strains, it is now possible to give better influenza vaccination recommendation for Cambodia.

Data mining in the US using the Vaccine Adverse Event Reporting System.

The US Vaccine Adverse Event Reporting System (VAERS), which is charged with vigilance for detecting vaccine-related safety issues, faces an increasingly complex immunisation environment. Since 1990, steady increases in vaccine licensing and distribution have resulted in increasing numbers of reports to VAERS. Prominent features of current reports include more routine vaccine co-administration and frequent reports of new postvaccination clinical syndromes. Data-mining methods, based on disproportionality analyses, are one strategy being pursued by VAERS researchers to increase the utility of its complex database. The types of analyses used include proportional reporting ratios, association rule discovery, and various 'historic limits' methods that compare observed versus expected event counts. The use of such strategies in VAERS has been primarily supplemental and retrospective. Signals for inactivated influenza, typhoid and tetanus toxoid-containing vaccines have been successfully identified. Concerns flagged through data mining should always be subject to clinical case review as a first evaluation step. Persistent issues should be subject to formal hypothesis testing in large linked databases or other controlled-study settings. Automated data-mining techniques for prospective use are currently undergoing development and evaluation within VAERS. Their use (as one signal-detection tool among many) by trained medical evaluators who are aware of system limitations is one legitimate approach to improving the ability of VAERS to generate vaccine-safety hypotheses. Such approaches are needed as more new vaccines continue to be licensed.

A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001.

PURPOSE: Post-licensure experience with a new intranasal inactivated influenza vaccine in Switzerland recently identified an increased risk for Bell's palsy. We reviewed reports in the Vaccine Adverse Event Reporting System (VAERS) to assess if parenteral inactivated influenza vaccines (influenza vaccines) may also increase the risk for Bell's palsy. METHODS: Reports of Bell's palsy after influenza vaccines in VAERS from 1/1/1991 to 12/31/2001 were identified by searching the Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) for 'paralysis facial' and by text string search in the automated database. The text descriptions on each report were reviewed to verify the diagnosis. The proportional reporting ratio (PRR) was calculated to aid signal detection. RESULTS: We found a total of 197 reports of Bell's palsy after receipt of influenza vaccines. The diagnosis was verified for 154 (78.2%), of which 145 (94.2%) had received influenza vaccines alone. The verified reports were submitted from 35 states; 58% of the reports involved persons living in states where the risk of Lyme disease, which can also cause facial paralysis, was low, minimal or none. The PRRs in all age groups exceeded the criteria for a signal of possible association. The highest PRR was 3.91 in the > or = 65 years age group. CONCLUSIONS: Our findings revealed a signal of possible association between influenza vaccines and an increased risk of Bell's palsy. A population-based controlled study is needed to determine whether this association could be causal and to quantify the risk.

Severe acute respiratory syndrome, Beijing, 2003.

The largest outbreak of severe acute respiratory syndrome (SARS) struck Beijing in spring 2003. Multiple importations of SARS to Beijing initiated transmission in several healthcare facilities. Beijing's outbreak began March 5; by late April, daily hospital admissions for SARS exceeded 100 for several days; 2,521 cases of probable SARS occurred. Attack rates were highest in those 20-39 years of age; 1% of cases occurred in children <10 years. The case-fatality rate was highest among patients >65 years (27.7% vs. 4.8% for those 20-64 years, p < 0.001). Healthcare workers accounted for 16% of probable cases. The proportion of case-patients without known contact to a SARS patient increased significantly in May. Implementation of early detection, isolation, contact tracing, quarantine, triage of case-patients to designated SARS hospitals, and community mobilization ended the outbreak.

Risk factors for SARS among persons without known contact with SARS patients, Beijing, China.

Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing's strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community's use of this strategy.

Superspreading SARS events, Beijing, 2003.

Superspreading events were pivotal in the global spread of severe acute respiratory syndrome (SARS). We investigated superspreading in one transmission chain early in Beijing's epidemic. Superspreading was defined as transmission of SARS to at least eight contacts. An index patient with onset of SARS 2 months after hospital admission was the source of four generations of transmission to 76 case-patients, including 12 healthcare workers and several hospital visitors. Four (5%) case circumstances met the superspreading definition. Superspreading appeared to be associated with older age (mean 56 vs. 44 years), case fatality (75% vs. 16%, p = 0.02, Fisher exact test), number of close contacts (36 vs. 0.37) and attack rate among close contacts (43% vs. 18.5%, p < 0.025). Delayed recognition of SARS in a hospitalized patient permitted transmission to patients, visitors, and healthcare workers. Older age and number of contacts merit investigation in future studies of superspreading.

Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland.

BACKGROUND: After the introduction of an inactivated intranasal influenza vaccine that was used only in Switzerland, 46 cases of Bell's palsy were reported. METHODS: We conducted a matched case-control study and a case-series analysis. All primary care physicians, ear, nose, and throat specialists, and neurologists in German-speaking regions of Switzerland were requested to identify cases of Bell's palsy diagnosed in adults between October 1, 2000, and April 30, 2001. Each physician was invited to select three control patients for each patient with Bell's palsy, with matching according to age, date of the clinic visit, and physician. Vaccination information was provided by the physicians. RESULTS: A total of 773 patients with Bell's palsy were identified. Of the 412 (53.3 percent) who could be evaluated, 250 (60.7 percent) were enrolled and matched with 722 control patients; the other 162 patients had no controls. In the case-control study, we found that 68 patients with Bell's palsy (27.2 percent) and 8 controls (1.1 percent) had received the intranasal vaccine (P<0.001). In contrast to parenteral vaccines, the intranasal vaccine significantly increased the risk of Bell's palsy (adjusted odds ratio, 84.0; 95 percent confidence interval, 20.1 to 351.9). Even according to conservative assumptions, the relative risk of Bell's palsy was estimated to be 19 times the risk in the controls, corresponding to 13 excess cases per 10,000 vaccinees within 1 to 91 days after vaccination. In the case-series analysis, the period of highest risk was 31 to 60 days after vaccination. CONCLUSIONS: This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy. This vaccine is no longer in clinical use.

Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001.

PROBLEM/CONDITION: Vaccines are usually administered to healthy persons who have substantial expectations for the safety of the vaccines. Adverse events after vaccinations occur but are generally rare. Some adverse events are unlikely to be detected in prelicensure clinical trials because of their low frequency, the limited numbers of enrolled subjects, and other study limitations. Therefore, postmarketing monitoring of adverse events after vaccinations is essential. The cornerstone of monitoring safety is review and analysis of spontaneously reported adverse events. REPORTING PERIOD COVERED: This report summarizes the adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) from January 1, 1991, through December 31, 2001. DESCRIPTION OF SYSTEMS: VAERS was established in 1990 under the joint administration of CDC and the Food and Drug Administration (FDA) to accept reports of suspected adverse events after administration of any vaccine licensed in the United States. VAERS is a passive surveillance system: reports of events are voluntarily submitted by those who experience them, their caregivers, or others. Passive surveillance systems (e.g., VAERS) are subject to multiple limitations, including underreporting, reporting of temporal associations or unconfirmed diagnoses, and lack of denominator data and unbiased comparison groups. Because of these limitations, determining causal associations between vaccines and adverse events from VAERS reports is usually not possible. Vaccine safety concerns identified through adverse event monitoring nearly always require confirmation using an epidemiologic or other (e.g., laboratory) study. Reports may be submitted by anyone suspecting that an adverse event might have been caused by vaccination and are usually submitted by mail or fax. A web-based electronic reporting system has recently become available. Information from the reports is entered into the VAERS database, and new reports are analyzed weekly. VAERS data stripped of personal identifiers can be reviewed by the public by accessing http://www.vaers.org. The objectives of VAERS are to 1) detect new, unusual, or rare vaccine adverse events; 2) monitor increases in known adverse events; 3) determine patient risk factors for particular types of adverse events; 4) identify vaccine lots with increased numbers or types of reported adverse events; and 5) assess the safety of newly licensed vaccines. RESULTS: During 1991-2001, VAERS received 128,717 reports, whereas >1.9 billion net doses of human vaccines were distributed. The overall dose-based reporting rate for the 27 frequently reported vaccine types was 11.4 reports per 100,000 net doses distributed. The proportions of reports in the age groups <1 year, 1-6 years, 7-17 years, 18-64 years, and >/= years were 18.1%, 26.7%, 8.0%, 32.6%, and 4.9%, respectively. In all of the adult age groups, a predominance among the number of women reporting was observed, but the difference in sex was minimal among children. Overall, the most commonly reported adverse event was fever, which appeared in 25.8% of all reports, followed by injection-site hypersensitivity (15.8%), rash (unspecified) (11.0%), injection-site edema (10.8%), and vasodilatation (10.8%). A total of 14.2% of all reports described serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability. Examples of the uses of VAERS data for vaccine safety surveillance are included in this report. INTERPRETATION: As a national public health surveillance system, VAERS is a key component in ensuring the safety of vaccines. VAERS data are used by CDC, FDA, and other organizations to monitor and study vaccine safety. CDC and FDA use VAERS data to respond to public inquiries regarding vaccine safety, and both organizations have published and presented vaccine safety studies based on VAERS data. VAERS data are also used by the Advisory Committee on Immunization Practices and the Vaccine and Related Biological Products Advisory Committee to evaluate possible adverse events after vaccinations and to develop recommendations for precautions and contraindications to vaccinations. Reviews of VAERS reports and the studies based on VAERS reports during 1991-2001 have demonstrated that vaccines are usually safe and that serious adverse events occur but are rare. PUBLIC HEALTH ACTIONS: Through continued reporting of adverse events after vaccination to VAERS by health-care providers, public health professionals, and the public and monitoring of reported events by the VAERS working group, the public health system will continue to be able to detect rare but potentially serious consequences of vaccination. This knowledge facilitates improvement in the safety of vaccines and the vaccination process.