From the Disease Investigations and Surveillance Branch, Division of Communicable Disease Control, California Department of Health Services, Sacramento, CA.
Received for publication November 5, 2001; accepted for publication July 22, 2002.
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ABSTRACT |
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cause of death; cost of illness; hospitalization; length of stay; population surveillance; Salmonella infections
Abbreviations: Abbreviations: AIDS, acquired immunodeficiency syndrome; ICD, International Classification of Diseases.
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INTRODUCTION |
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Infection with nontyphoidal Salmonella usually results in a self-limiting gastroenteritis that does not require antibiotic therapy, but severe clinical consequences can include septicemia, arthritis, meningitis, and pneumonia (10, 11). The very young, elderly, and immunocompromised are at increased risk of complications or death. Evidence of increasing antimicrobial resistance is of concern when treating extraintestinal infections (12).
The incidence of reported salmonellosis in the United States has decreased in recent years (13). Outbreaks still occur, particularly of Salmonella Enteritidis, which accounted for the largest number of outbreaks, cases, and deaths among nationally reported outbreaks from 1993 through 1997 (14, 15). Surveillance data allow estimation of overall incidence and trends, although underreporting and the lack of information on disease severity limit the usefulness of these data (16). The purpose of the current study is to describe the epidemiology of nontyphoidal salmonellosis in California, including estimates of the hospitalization costs. To this end, several population-based data sources were examined, including statewide surveillance data, hospital discharge data, and death records.
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MATERIALS AND METHODS |
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Hospital discharge data were obtained from the California Office of Statewide Health Planning and Development for 1990 through 1999 (17). These data contain information on about 3.5 million yearly discharges from all civilian hospitals in California, except state hospitals for patients with mental disorders or developmental disabilities, and federal facilities. Discharge records containing the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, code for nontyphoidal Salmonella infection (code 003) as the principal diagnosis or one of the 24 additional diagnoses were selected for analysis.
The Death Public Use file (19901999) and the Multiple Cause of Death tapes (19901997), which contain death certificate data, were obtained from the Center for Health Statistics of the California Department of Health Services (18, 19). The former contains only the underlying cause of death, while the latter contain both the underlying and up to 20 multiple causes of death. The record-axis codes were used to identify the multiple causes of death. Deaths among California residents with an ICD, Ninth Revision, code 003 or an ICD, Tenth Revision, code A20 (Salmonella infection other than typhoid and paratyphoid) as a cause of death were included.
Data analysis
The average age-, race/ethnicity-, and sex-specific incidence rates (cases per 105 person-years) were calculated using the 1995 California population projections (20). These estimates were adjusted to account for cases with missing demographic data by assuming that the proportion with missing data is the same within each subgroup. Cases with race/ethnicity reported as "other" were classified as missing for calculation of race/ethnicity-specific rates. Confidence intervals (95 percent) for proportions were calculated for each group-specific rate; differences were considered significant if the confidence intervals did not overlap. Annual incidence rates were calculated using official California population estimates (21).
Temporal trends in incidence rates were evaluated using Poisson regression models. The fits of models containing year as a single continuous variable, a quadratic function, and a third-order polynomial were each evaluated using a chi-square goodness-of-fit test. An F-to-remove test, based on the difference in the residual deviance between models, was used to evaluate the contribution of the time variables. Values of p < 0.05 were considered significant.
Hospital discharge records containing cost data were used to estimate the total costs for all salmonellosis-associated hospitalizations, assuming that reported costs were comparable with those for hospitals that do not report cost. The average number of salmonellosis-associated hospitalization days per year was estimated by multiplying the average length of stay by the average number of hospital discharges per year.
Relations between the variables in table 1 and length of stay were evaluated using linear regression analysis. Only records with no missing values for the listed variables or length of stay were included. To minimize dependence among observations, we included only the first hospitalization of patients with more than one Salmonella-associated hospitalization. Patients with multiple hospitalizations were identified using the record linkage number, which is an encrypted Social Security number. Patients with no record linkage number were assumed to have been hospitalized only once. The analysis of race/ethnicity, payment source, and site of infection was limited to the categories listed in table 1 because of the small number of patients in the other categories. The distribution of length of stay was skewed because of the small proportion of patients hospitalized for extended periods. To improve the normality of the data, we excluded patients with no overnight stay (length of stay = zero) or length of stay of more than 14 days; for the remaining observations, the length of stay was transformed by taking the natural logarithm of length of stay + 10. Models were compared using the F-to-remove test as described above. Values of p < 0.05 were considered significant. The decision to retain variables in the final model was based on both the biologic plausibility and statistical significance of the putative risk factor. The model coefficients were exponentiated to determine the percentage of change in length of stay associated with a one-unit change in the factor. The distribution of the normalized residuals was inspected to evaluate how well the assumptions of the linear regression model were met. In addition, all possible two-way interaction terms were considered.
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RESULTS |
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The charge per hospitalization ranged from $160 to $3,182,847 (median: $9,054). All hospitalizations with missing cost data (9.5 percent) were from Kaiser Foundation hospitals. The most common single sources of payment for hospitalizations were private insurance (34 percent), Medi-Cal (32 percent), and Medicare (24 percent). The majority of hospitalizations (54 percent) were paid by government sources (Medi-Cal, Medicare, Workers Compensation, and others), accounting for more than $114 million in reported charges over the 10-year period. The total cost for all Salmonella-associated hospitalizations over the 10-year period, after adjusting for hospitalizations with no charge reported, was estimated at over $200 million.
An analysis of hospitalizations by site of Salmonella infection identified gastroenteritis (61 percent) as the most common diagnosis, followed by septicemia (23 percent) (table 3). Patients with Salmonella meningitis had the lowest median age (0.3 years) while those with Salmonella pneumonia had the highest (55 years). The median cost per hospitalization ranged from $7,412 for gastroenteritis to nearly $30,000 for meningitis and pneumonia. The most commonly occurring comorbid conditions among hospitalized Salmonella patients are listed in table 4.
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Of the 11,102 hospitalizations, 9,820 (88 percent) were assumed to represent patients hospitalized only once with salmonellosis; 6,781 were identified as such using the record linkage number, and 3,039 were assumed to be because the record linkage number was missing. Using the record linkage number, which was reported for 8,063 (74 percent) hospitalizations, we identified 719 as repeat hospitalizations (i.e., subsequent hospitalizations among patients with two or more Salmonella-associated hospitalizations). The following linear regression analysis, which examines factors associated with length of stay, is restricted to patients hospitalized only once or the first hospitalization for patients hospitalized more than once. After excluding ineligible records, there were 8,028 discharge records remaining for linear regression analysis.
Although many factors were found to be significantly associated with length of stay, the percentage of change in length of stay associated with a one-unit change in these factors was appreciable in only a few instances (table 5). Notably, a diagnosis of acquired immunodeficiency syndrome (AIDS) increased the length of stay by 17.3 percent compared with patients without AIDS. Patients with more than one Salmonella diagnosis had a length of stay that was 11.3 percent higher than that of patients with one Salmonella diagnosis. Patients with Salmonella gastroenteritis had a length of stay that was 10.2 percent less than that of patients with other sites of Salmonella infection. The length of stay decreased an average of 8.6 percent per year over the 10-year period examined.
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Examination of the observed versus predicted observations demonstrated that the fit of model was not as close for small and large values of length of stay. The residuals appeared normally distributed; however, closer examination of the outlier residuals indicated that the fit of the model was not as close for extreme values of length of stay, particularly for small values of length of stay (less than three), resulting in a slight excess of negative residuals (4 percent).
Death records
From 1990 through 1999, there were 74 deaths with Salmonella infection reported as the underlying cause (table 2). Forty-four of the deaths (59 percent) occurred among persons aged 65 or more years. Salmonella septicemia, reported in 42 of the 74 deaths (57 percent), was the most common type of infection (table 3).
From 1990 through 1997, there were 130 deaths reported with Salmonella reported as the underlying or multiple cause of death, 62 percent of which occurred among men (table 2). Seventy of the deaths (54 percent) occurred among persons aged 65 or more years. Salmonella septicemia, reported in 73 of the 130 deaths (56 percent), was the most common type of infection (table 3).
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DISCUSSION |
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Although serotype data were not available in the data sets examined for the current study, these data were available from the Microbial Diseases Laboratory of the California Department of Health Services, which is supposed to receive all human Salmonella isolates in California for serotyping. The annual number of Salmonella isolates received decreased from 1993 through 1999, driven largely by a decrease in Salmonella Enteritidis submissions. Salmonella Enteritidis was the most common Salmonella for each year examined, except 1993, when Salmonella Typhimurium was more common. However, the proportion of Salmonella Enteritidis isolates significantly decreased over the period examined (chi-square for linear trend = 35.60, p < 0.01) (California Department of Health Services, unpublished data).
Foodborne outbreaks reported in California during the study period provide an interesting comparison with current findings. Both individual Salmonella cases and foodborne outbreaks are reportable at the state and national levels. Although the incidence of reported Salmonella cases has decreased, the number of reported Salmonella outbreaks has consistently increased, from a low of four in 1990 to a high of 32 in 1999, due largely to Salmonella Enteritidis outbreaks, the most common outbreak-related serotype (California Department of Health Services, unpublished data). The increase in the number of reported Salmonella outbreaks may be due to increased awareness, better surveillance, an increase in conditions favorable to outbreaks, or a combination of these factors.
It is possible that outbreak-related cases influenced the observed trend in the incidence of reported cases. Because case reports from patients who were part of an outbreak are not always identified as such, it is not possible to ascertain the proportion of outbreak-related cases that get reported as individual cases. Assuming that no case reports were submitted for outbreak-related cases, we added the number of outbreak-related cases per year to the annual number of reported cases, and the trend in the incidence was examined as previously described. Conversely, assuming that all outbreak-related cases were reported as individual cases, we subtracted the number of outbreak-related cases per year from the annual number of reported cases to remove their influence on the observed trend. In neither case was there an appreciable change in the observed trend. In reality, the number of outbreak-related cases that also get reported as individual cases is intermediate between these two scenarios.
The elderly (65 years) and young children (<5 years) were disproportionately affected by salmonellosis, with a greater proportion of deaths among the former, higher rates of reported cases among the latter, and higher hospital discharge rates for both. Over half of the decedents with Salmonella listed as a cause of death were elderly, although this age group accounts for only 11 percent of Californias population. Approximately 25 percent of all reported cases were among young children, although they account for only 10 percent of the population. The disproportionate impact of gastrointestinal and invasive disease among the elderly and children has been noted in previous studies (2426). The previously described susceptibility of infants to Salmonella meningitis was supported by the hospital discharge data in the current study (27). Persons with immunocompromising illnesses, such as AIDS, cancer, and diabetes, are also known to suffer a disproportionate share of severe Salmonella-associated complications and death (28, 29).
The observed temporal trend of decreasing length of stay may reflect improved treatments, managed care efforts, or both. In general, the length of stay for AIDS patients was greater than for those without AIDS. The decreased length of stay among AIDS patients with Salmonella septicemia or other specified Salmonella infections is more difficult to interpret but may be the result of more aggressive management in these patients, efforts to minimize the length of stay to reduce the risk of nosocomial infection, or a spurious finding. Patients with Salmonella gastroenteritis had a shorter length of stay compared with patients with other types of Salmonella infections, which is expected given the typically self-limiting nature of gastroenteritis. Similarly, patients with only one Salmonella diagnosis had a length of stay that was shorter compared with patients with more than one Salmonella diagnosis. Although many factors were found to be significantly associated with length of stay using this multiple linear regression model, the actual percentage of change in the length of stay associated with a one-unit change in many of these factors was not appreciable. Given the large number of observations included in the linear model (n = 8,028), it is quite possible that very small and potentially unimportant associations would yield statistically significant results.
The surveillance data used in the current study probably underestimate the true incidence of Salmonella-associated morbidity for several reasons. To be identified as a Salmonella case, a person must be symptomatic, consult a health care provider, and provide a clinical specimen that is laboratory confirmed as positive for Salmonella. To be counted as a case, the health care provider or laboratory must initiate a report to the local health department before it enters the surveillance channels. The degree of underreporting of Salmonella infection has been estimated to be from 19- to 38-fold (16, 30). This is not unexpected given that an estimated 50 percent of persons with intestinal infectious disease would neither consult a physician nor experience a full day of restricted activity (31). New initiatives to enhance electronic reporting by laboratories are likely to improve surveillance efforts from that end.
The California surveillance data for salmonellosis were often lacking demographic data, particularly prior to 1993, when many local health departments submitted only summary counts of Salmonella cases. To estimate the demographic characteristics of all reported cases, we assumed that those with missing demographic data were similar in makeup with those with complete data, which may not be valid. For instance, if certain subgroups are less likely to have their demographics reported, the reporting rates provided for these groups will be underestimates. Because race/ethnicity was reported for only 68 percent of reported Salmonella cases, these estimated race/ethnicity-specific rates may be seriously biased. With the advent of electronic reporting over the Internet, it will be possible to include prompts to encourage the submitter to furnish these data, which should increase the reporting completeness for key data fields. Even when demographic data are reported, they are still subject to misclassification (32).
The use of hospital discharge data to estimate hospitalization costs produces conservative estimates. Reported costs do not include hospital-based physician fees, charges for outpatient or posthospitalization care, or over-the-counter medications. Also not considered are lost productivity or lost earnings due to missed work or premature death. Previously published national estimates of the annual costs of medical care and lost productivity due to foodborne Salmonella infections ranged from $0.5 to $2.3 billion (33). Hospitalization costs were not reported for patients discharged from Kaiser Foundation hospitals, which are affiliated with the largest health maintenance organization in California that provides insurance coverage for approximately 18 percent of Californians. Extrapolation from records with available cost data was used to estimate the total hospitalization costs in California during the 10-year period at over $200 million. This could be a biased estimate if Kaiser hospitalization costs differ systematically from those of other hospitals.
The sensitivity and specificity of the diagnoses provided in the hospital discharge records are unknown. The means of diagnosis, such as results of laboratory tests, are unknown. The possibility of coding errors during data entry also exists. Furthermore, if a condition is undiagnosed or is mistakenly not entered into the discharge record, misclassification of the patients disease status for that condition will result. For example, in the current study there were 469 Salmonella-associated hospitalizations with a concurrent diagnosis of candidiasis, a frequent opportunistic infection among AIDS patients. Because AIDS was listed as a diagnosis for only 205 (44 percent) of the 469 candidiasis-associated hospitalizations, it is possible that some patients with candidiasis had undiagnosed or unreported AIDS.
Another limitation of the hospital discharge data is the lack of the record linkage number for some patients. When available, the record linkage number allowed identification of patients with multiple Salmonella-associated hospitalizations. Patients with a missing record linkage number were assumed to have been hospitalized only once with salmonellosis, which is likely to result in an underestimate of the number of patients with multiple hospitalizations. However, if the proportion of subsequent hospitalizations among patients with a missing record linkage number is similar to that among those with a record linkage number reported (9 percent), the effect would be small. Subsequent hospitalizations, which may be due to reinfections or the reappearance of symptoms in a person with prolonged infection, are one measure of the degree of severity of the illness. The availability of an encrypted version of patients names would permit identification of patients with repeated hospitalizations when the record linkage number is missing.
A direct comparison between death record and hospital discharge data was limited by the availability of only four digits of the ICD, Ninth Revison, code in the former data set. As a result, it was not always possible to discern the site of infection for decedents with as much specificity as allowed by the hospital discharge data, which provide the ICD, Ninth Revision, Clinical Modification, codes up to five digits. The California Office of Statewide Health Planning and Development is currently developing a linked data set of death records and the corresponding hospital discharge records, which should allow more ready comparisons of these records. The death records may underrepresent Salmonella-associated deaths, especially in instances where culture confirmation is lacking. However, these data do clearly indicate the disproportionate impact of fatal disease among the elderly.
These findings demonstrate a sizeable public heath and economic impact associated with salmonellosis in California. There is evidence of a significant decrease in the incidence of both reported cases and hospitalizations over the last few years, which is corroborated by active surveillance data collected in two California counties. This decreasing trend is also observable at the national level. Although the purpose of the current study was not to identify the causes of the observed trends, there are several factors that may have contributed to this decline. For instance, increasing media coverage and public concern regarding food safety over recent years may have improved food-handling practices by consumers. In 1996, the US Department of Agriculture introduced new meat inspection and hazard analysis and critical control point guidelines aimed at reducing the contamination of meat, poultry, and eggs by enteric pathogens. In addition, improvements in therapy for AIDS patients, such as the introduction of highly active antiretroviral therapy, have been effective in reducing opportunistic infections among AIDS patients (34).
Further follow-up will determine if the recent downward trend will continue. Although industrial food sanitation practices have improved, outbreaks of salmonellosis attributable to contaminated food products still occur. Measures to improve consumer awareness of the importance of proper cooking and food handling are still important in decreasing the individual risk and consequently the incidence of salmonellosis. Further research and interventions are especially needed to understand the risk factors and to reduce the incidence and adverse sequelae among young children and the elderly.
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NOTES |
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REFERENCES |
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