The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions.

Contribution of second stool specimen to increased sensitivity of poliovirus detection in India, 1998-2000.

Acute flaccid paralysis (AFP) surveillance data from India were analysed to examine sensitivity of poliovirus isolation from stool specimens and the added sensitivity obtained from collection of a second stool specimen. Analysis was restricted to Indian AFP cases, 1998-2000, with two adequate stool specimens. The proportion of cases confirmed with wild poliovirus isolation by the second specimen only was calculated, regardless of specimen quality. Overall specimen sensitivity (1998-2000) was 81% using the first specimen, 78% using the second, and 96% using both. Sensitivity increased from 1998 to 2000, with slightly higher sensitivity each year for the first specimen. The second specimen increased sensitivity by 15% overall and contributed more when the first specimen was collected late or was in poor condition. As wild poliovirus disappears, increased sensitivity provided by a second stool specimen may reduce the risk of missing circulating virus.

Mass measles vaccination in urban Burkina Faso, 1998.

OBJECTIVE: To assess the impact of the National Immunization Days (NIDs) on measles vaccine coverage in Burkina Faso in 1998. METHODS: During the week after the campaign, in which measles vaccine was offered to children aged 9-59 months in six cities regardless of vaccination history, a cluster survey was conducted in Ouagadougou and Bobo Dioulasso, the country's two largest cities. Interviewers visited the parents of 1267 children aged up to 59 months and examined vaccination cards. We analysed the data using cluster sample methodology for the 1041 children who were aged 9-59 months. FINDINGS: A total of 604 (57%) children had received routine measles vaccination prior to the campaign, and 823 (79%) were vaccinated during the NIDs. Among those who had previously had a routine vaccination, 484 (81%) were revaccinated during the NIDs. Among those not previously vaccinated, 339 (78%) received one dose during the NIDs. After the campaign, 943 (91%) children had received at least one dose of measles vaccine. Better socioeconomic status was associated with a higher chance of having been vaccinated routinely, but it was not associated with NID coverage. CONCLUSION: The mass campaign enabled a substantial increase in measles vaccine coverage to be made because it reached a high proportion of children who were difficult to reach through routine methods.

The burdens of uninsured hospitalizations in an urban county.

CONTEXT: Few data at the level of local health jurisdictions are available to characterize health problems specific to persons without health insurance. PRACTICE PATTERN EXAMINED: Hospitalization patterns of residents of DeKalb County, Georgia, who have no health insurance. DATA SOURCE: 1996 Georgia hospital discharge records for persons living within ZIP code areas included in or overlapping with DeKalb County. RESULTS: Of 67,156 hospital discharges, 6781 (10%) were for uninsured patients. Sixty-eight percent of uninsured hospitalizations took place in publicly owned and controlled hospitals, where uninsured persons represented 45% of all discharges. Charges associated with uninsured hospitalizations amounted to $51.3 million in 1996, of which $35.3 million (69%) was claimed by public hospitals. The uninsured were overrepresented in many diagnostic groups, including diabetes, injury and poisoning, chronic liver disease, skin disease, and infectious or parasitic disease. CONCLUSIONS: In DeKalb County, Georgia, the burden of uninsured hospitalizations falls disproportionately on the public sector. Policy initiatives are needed to more equitably share the burden of uninsured hospitalization with for-profit hospitals. Because the uninsured were overrepresented in several conditions, public health initiatives aimed at preventing these conditions should also be a priority.

Disparities in hospital utilization in an urban county: use of local consumer marketing data for priority setting.

National data sets are often insufficient for priority setting by local public health systems and the communities they serve. We used marketing data to conduct an ecological analysis of hospital discharge rates in DeKalb County, Georgia, during 1996. Persons living in poorer areas had significantly higher discharge rates for the following conditions: hypertensive disease, blood-related conditions, pneumonia/influenza, diabetes, and chronic obstructive pulmonary diseases. Local marketing data helped identify conditions associated with higher hospital utilization in poorer areas of this urban county. This identification of priority issues informs plans for behavior modification, access to primary care and a healthy environment.

Increased risk of Mycobacterium tuberculosis infection related to the occupational exposures of health care workers in Chiang Rai, Thailand.

SETTING: Chiang Rai, the northernmost province of Thailand. OBJECTIVE: To evaluate the occupational risk for tuberculous infection of health care workers (HCWs) and the utility of tuberculin skin test (TST) in a developing country setting. DESIGN: A cross-sectional TST survey, including a risk assessment questionnaire, of Chiang Rai Hospital HCWs. RESULTS: Of 911 HCWs tested, 623 (68%) had indurations of > or = 10 mm and 322 (35%) indurations of > or = 15 mm. Factors most predictive for TST positivity, using either cut-off, were employment > 1 year, frequent direct patient contact, and male sex. Moreover, having a bacillus Calmette-Guérin (BCG) scar was predictive of a > or = 10 mm, but not a > or = 15 mm, reaction. CONCLUSIONS: Chiang Rai Hospital HCWs had an increased risk for Mycobacterium tuberculosis infection, which was significantly associated with occupational exposure. Where BCG coverage is high, a TST cut-off of > or = 15 mm may correlate better with M. tuberculosis infection than does a cut-off of > or = 10 mm. Effective, affordable infection control measures are needed for health care facilities in developing countries such as Thailand, where HCWs may be at increased risk for M. tuberculosis infection from occupational exposures.

Tuberculosis among foreign-born residents of southern Florida, 1995.

OBJECTIVE: To examine the characteristics of foreign-born people with tuberculosis (TB) in Southern Florida, their contribution to the total number of TB cases, and available data on their HIV status as well as to determine the number of cases detected by the overseas medical screening of immigrants and refugees. METHODS: The authors reviewed TB cases reported by Broward, Dade, and Palm Beach counties in 1995. Case records were matched against the CDC Division of Quarantine database of immigrants and refugees suspected to have TB at the time of visa application overseas. RESULTS: Nearly half (49%) of TB cases in the three counties were among people born outside the United States--34% in Broward County, 58% in Dade County, and 40% in Palm Beach County. A high percentage (26%) were co-infected with HIV. Of those with known date of arrival, 68% had been in the United States for five or more years. Only three cases had been identified by overseas immigrant screening. CONCLUSIONS: A low percentage of TB cases in foreign-born people were identified through the overseas screening system. Controlling TB in South Florida will require efforts targeted toward high risk populations, including people with HIV infection.

Tuberculosis prevention among foreign-born persons in Seattle--King County, Washington.

The purpose of this study was to evaluate the outcomes of classified immigrant and refugee (I&R) screening and of contact investigation (CI) of foreign-born TB cases in Seattle--King County (SKC), Washington. We reviewed I&R evaluations from the SKC TB clinic for 1992-1994 and contact evaluation records for 54 randomly selected U.S.-born and foreign-born pulmonary TB patients from 1993. Among 942 I&R evaluated, 693 (74%) had positive tuberculin skin tests (TST). Preventive therapy (PT) was prescribed for 324 (34%) and treatment for 49 (5%). The remaining 377 were dismissed, of whom 96% did not meet American Thoracic Society PT criteria. Contacts of foreign-born cases were more numerous (6.0 versus 3.4 per case, p = 0.04), and significantly more likely to be TST-positive (50% versus 18%) and to be started on PT (40% versus 23%). The large number of I&R eligible for treatment or PT emphasizes the benefit of prompt evaluation of new arrivals. CI provides an excellent opportunity to screen foreign-born persons at high risk for active TB.

Long-term risk of tuberculosis among foreign-born persons in the United States.

CONTEXT: Cases of tuberculosis (TB) in the United States have declined for 4 consecutive years, but cases among foreign-born persons account for an increasing percentage. OBJECTIVE: To describe the risk of tuberculosis among foreign-born persons with respect to their length of residence in the United States. DESIGN: Cross-sectional analysis of national surveillance data. SETTING: The United States. PATIENTS: All verified TB cases reported to the Centers for Disease Control and Prevention between 1986 and 1994. MAIN OUTCOME MEASURE: Stratum-specific incidence rates of TB by age, place of birth, length of residence, age at arrival in the United States, or combinations of these variables. RESULTS: Several groups of persons from countries with a high prevalence of TB had incidence rates higher than 20 per 100,000 person-years more than 20 years after arrival. Among long-term residents, those who arrived in the United States after their fifth birthday had incidence rates of TB 2 to 6 times higher than those of similar age who arrived before their fifth birthday. A total of 45% of the TB cases were among persons younger than 35 years and an additional 18% were among persons who arrived in the United States before their 35th birthday. CONCLUSIONS: Imported Mycobacterium tuberculosis infection (active or latent) is responsible for most TB cases among foreign-born persons in the United States. Detection of active cases among recent arrivals is the main priority in these populations, but many cases were in persons who arrived in the United States before the age of 35 years that could potentially have been avoided with preventive therapy. Elimination of TB in the United States may not be feasible using available diagnostic and treatment modalities without increased efforts to address the global burden of this disease.

Overseas screening for tuberculosis in immigrants and refugees to the United States: current status.

The number of reported cases of tuberculosis (TB) in foreign-born persons in the United States during 1995 was 8,042, 36% of the national total. The overseas screening of immigrants and refugee visa applicants, which relies on a chest radiograph and smear microscopy, is designed to identify future U.S. residents who have active TB or who are at high risk for TB. In this commentary, we summarize current policies and review retrospective evaluations of the screening system currently in place. The system appears to detect most persons who have active TB at the time of screening. However, active TB is actually diagnosed in < 15% of persons who are identified by screening as having suspected TB and who are evaluated in the United States. To improve the system, more sensitive and specific techniques as well as improved means of data transmission to state and local health departments are needed.

Tuberculosis among foreign-born persons in Los Angeles County, 1992-1994.

OBJECTIVES: To describe the epidemiology of foreign-born tuberculosis (TB) cases in Los Angeles County and to evaluate current TB screening and follow-up of immigrants and refugees (I&R) to the USA. DESIGN: Retrospective analysis of the Los Angeles County TB registry between October 1992 and December 1994. We matched all cases who entered the USA during fiscal year 1993 (FY93) with a database from the tracking system of I&R with suspected TB. RESULTS: Foreign-born persons accounted for 64% of all reported TB cases. Half were born in Mexico or Central America. Standardized incidence rates were 3-5 times higher than those of US-born persons for Mexicans and Central Americans, 6-7 times higher for North-east Asians, and 10-15 times higher for South-east Asians. Among foreign-born cases who arrived during FY93, 5% of the Mexicans and Central Americans, 48% of the North-east Asians and 67% of the South-east Asians were registered by the tracking system. CONCLUSION: Mexicans and Central Americans accounted for the majority of cases but had a lower incidence of TB than Asians. The current screening procedures identify a large proportion of cases among recently arrived South-east Asians, but contribute little to the control of TB among Mexicans and Central Americans.

Research issues involving HIV-associated tuberculosis in resource-poor countries.

Each year, there are an estimated 8 million new cases of tuberculosis (TB) and 3 million deaths due to TB, most of which occur in resource-poor countries. Tuberculosis incidence is increasing rapidly in countries with high rates of human immunodeficiency virus (HIV) infection, and despite the availability of effective interventions, many TB programs are failing to cope with the increased TB caseload. This report highlights gaps in current understanding of the interaction between TB and HIV that contribute to failure of optimal TB management and control; we focus on the diagnosis of TB, its epidemiology and transmission, preventive strategies, and programmatic issues in the integration of HIV and TB services. Research into how best to apply existing knowledge will be at least as important as searching for new knowledge. The global control of TB will also require increased resources, greater political commitment, and stronger international public health leadership.

Tuberculosis screening for immigrants and refugees. Diagnostic outcomes in the state of Hawaii.

The effectiveness of the required overseas tuberculosis (TB) screening for immigrants and refugees to the United States has not been evaluated since new guidelines were introduced in 1991. Using data from the Hawaii State TB register for 1992-1993, patient records, and data from the U.S. government notifications of suspect TB among aliens, we determined the percentage of persons either classified as having active TB (B1), inactive TB (B2), or considered "normal" overseas, who were evaluated and subsequently diagnosed with active TB within 1 yr of arrival in the United States. Of the 124 TB cases among immigrants and refugees evaluated within 1 yr of arrival, 78 (63%) had been classified overseas as B1, 17 (14%) as B2, and 29 (23%) as "normal." The proportion of TB cases diagnosed after arrival in the United States was 14.0% for B1s and 2.1% for B2s. This proportion decreased with increasing age. A positive skin test was a strong predictor (OR: 10.7; 95% CI: 1.4-80.1) of culture-confirmed TB. These data document that immigrants and refugees with B1 and B2 TB status have a high prevalence of active TB. They should be promptly evaluated after arrival in the United States to determine the need for curative or preventive therapy.

Seroprevalence of HBV (anti-HBc, HBsAg and anti-HBs) and HDV infections among 9006 women at delivery.

Serum samples from 9006 women, who delivered in Switzerland in 1990 and 1991, were collected around the country. Of these women, 62.7% were Swiss and 37.3% originated from foreign countries. Samples were first screened for anti-HBc and those found positive were further tested for HBsAg, anti-HBs and anti-HDV. Anti-HBc was found in 640 of the 9006 women (overall prevalence, 7.1%; Swiss, 3.3%; foreigners, 13.5%). Of these 640 positive samples, 61 (9.5%) were positive for HBsAg (without anti-HBs), 467 (73.0%) positive for anti-HBs (without HBsAg) and 8 (1.3%) positive for both HBsAg and anti-HBs. The remaining 104 were thus anti-HBc positive without HBsAg or anti-HBs. These 104 specimens with the so-called "isolated anti-HBc" reactivity represented 1.2% of the whole population or 16.3% of the 640 anti-HBc positive mothers. All were HBV DNA negative (PCR). Anti-HDV antibody was found in only five women. HBsAg was seen in 38 of the cord-blood samples from the anti-HBc positive mothers. In this large sampling, we observed a relatively high seroprevalence of HBV infection. Cases with isolated anti-HBc reactivity, being HBV DNA negative by PCR, were probably non-infectious at the time of blood collection.

Seroprevalence of rubella among women of childbearing age in Switzerland.

A seroepidemiological study was carried out in Switzerland to define the population susceptible to rubella among women of childbearing age. IgG antibodies to rubella virus were determined in 9,046 women giving birth between 1 August 1990 and 30 September 1991 in 23 of 26 Swiss cantons. These sera represented 10-20% of the yearly total number of births in each Swiss canton. Anti-rubella IgG was measured by an automated enzyme-linked fluorescent assay for use with a commercial system (Vidas Rub IgG, bio-Mérieux, France). Before the study population was screened, the commercial system was compared to the traditional hemagglutination-inhibition (HAI) test using 500 consecutive samples from parturient women. The sensitivity was 97.7%, the specificity was 100%, and agreement between the two tests was 97.8%. The discrepancies corresponded to very low titres of antibodies as measured by HAI. The seroprevalence of rubella nationwide in women of childbearing age in Switzerland was 94.3%. The seroprevalence was higher (96.5%) in the 5,677 women of Swiss nationality than in the 3,090 women of a different nationality (90.4%) (p < 0.001). In Swiss women the seroprevalence of rubella did not increase significantly with age and was identical in primiparous and in multiparous women, thus indicating that women of childbearing age are probably not sufficiently immunised.

Toxoplasma infection among pregnant women in Switzerland: a cross-sectional evaluation of regional and age-specific lifetime average annual incidence.

A simple generalized linear model of toxoplasmosis incidence has been applied to serologic data from more than 9,000 women who delivered babies in Switzerland. This model, based on an assumption of constant incidence of toxoplasmosis throughout time and ages, yields estimates of incidence rates that show marked contrasts between subgroups of women categorized on the basis of their geographic origin and duration of residence in Switzerland. The patterns observed are in agreement with previously reported data from specific areas. When applied to Swiss resident women of different age groups, the average incidence rate estimates obtained were remarkably similar. This was not the case among the subgroup of Portuguese immigrant women, nor when the model was applied to previously published data from Sweden where toxoplasmosis incidence has clearly decreased in the last 20 years. Although models for the analysis of cross-sectional data involve major simplifying assumptions, it appears that they can yield useful epidemiologic information and that departures from the assumed simplified structure of the data can sometimes be identified.

Tetanus in Switzerland 1980-1989.

Tetanus cases that occurred in Switzerland between 1980 and 1989 have been reviewed with the help of three data surveillance systems: a) morbidity data from the Federal Office of Public Health (FOPH), b) mortality data from the Swiss Federal Statistical Office (SFSO), and c) data from the Association of Swiss Hospitals and Clinics (VESKA), completed by a written enquiry to clinics which did not (or only partly) participate in the VESKA system during the study period. For every case, a questionnaire was sent to the clinic to verify the diagnosis and to obtain additional information on the circumstances of occurrence. Ninety-one cases were identified. This corresponds to a yearly incidence of 1.93 per million population between 1980-84 and 0.88 for the 1985-89 period (p < 0.01). Eighty-one percent of the cases were older than 50 years of age and women were significantly more frequently affected than men. None of the cases identified had a documented primary immunization series. Data available at the FOPH and SFSO level have been compared to data obtained through the VESKA system using the Chandra Sekhar and Deming method. It is estimated that 134 tetanus cases (95% CI: 91-197) have occurred in Switzerland between 1980 and 1989, together with 28 deaths (95% CI: 27-31). Based on these estimates, FOPH appears to detect only 6-13% of tetanus cases occurring in Switzerland. By contrast, SFSO had fairly consistent data for 81-100% of tetanus associated deaths. The low rate of tetanus reported by physicians necessitates a sustained effort to increase the understanding of epidemiological surveillance by Swiss practitioners.

Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries.

To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).