1 Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
2 National Health and Environmental Effects Laboratory, Environmental Protection Agency, Research Triangle Park, NC.
3 Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Received for publication December 13, 2001; accepted for publication July 24, 2002.
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ABSTRACT |
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gastroenteritis; intestinal diseases; mortality
Abbreviations: Abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HIV, human immunodeficiency virus; ICD-9, International Classification of Diseases, Ninth Revision; MCD, multiple cause of death; RR, relative risk.
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INTRODUCTION |
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During the 20th century, rates of death due to enteric diseases plummeted, largely because of disinfection of drinking water. In 1900, 8.3 percent of all deaths were due to the broad cause of gastritis (including diarrhea, enteritis, and colitis), but by 1990 all infectious diseases (respiratory as well as gastrointestinal) accounted for only 1.8 percent of deaths (4). In 1900, 31.3 deaths per 100,000 population were due to typhoid and paratyphoid fever (5) (International Classification of Diseases, Ninth Revision (ICD-9), code group 002). By 1920, typhoid and paratyphoid fever death rates had been reduced more than threefold to only 7.6 deaths per 100,000 population, partly because of disinfection and filtration of community water supplies. Deaths from typhoid and paratyphoid fever dropped below 0.05 per 100,000 population in 1953 and have remained at that level since then (5). During that same time span, deaths due to gastritis, duodenitis, enteritis, and colitis dropped from a high of 142.7 per 100,000 population in 1900 to less than 1 per 100,000 population beginning in 1968 (and continuing through 1996) (5).
Thus, the impact of enteric diseases on mortality has been greatly reduced over the last century. However, the proportion of Americans who are at high risk for severe enteric disease because of low immunity or advanced age is increasing each year.
Using national mortality data, we made a quantitative estimate of the numbers of endemic and epidemic deaths related to microbial-enteric disease in the United States from 1989 to 1996. Specific goals of this study were to estimate age-specific reporting rates of microbial-enteric diseases as causes of death and to investigate regional and etiologic trends in reporting rates of these diseases in relation to deaths in the United States.
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MATERIALS AND METHODS |
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Two sets of codes on conditions considered contributing causes of death are included for each data record in the MCD files. The original death certificate coding is preserved in the entity-axis codes, while the record-axis codes have been edited by the National Center for Health Statistics to eliminate contradictions and to define the condition most precisely within the limitations of ICD-9 coding and the available medical information on the death certificate (6).
Record-axis codes are used by the National Center for Health Statistics for the published MCD statistics. The ordering of codes within each record is not the same as it appeared on the death certificate, and this should not be considered relevant information. Record-axis codes represent the most meaningful codes for the reported condition, but some detail has been removed from the entity code for that record. ICD-9 category titles apply directly to record-axis codes. For example, a decedent with entity codes ICD-9 571.5 (cirrhosis of the liver without mention of alcohol) and ICD-9 303 (alcohol dependence syndrome) would have those codes replaced in the record-axis data by ICD-9 571.2 (alcoholic cirrhosis of the liver) (6). This analysis used the record-axis codes from the MCD files.
Poisson regression was used to estimate relative risks for possible predictors of enteric disease, including age group, sex, race, and US Census region.
Analysis
The MCD data were categorized by decedent age, race, and US Census region and then analyzed for reports of enteric disease. Four broad ICD-9 code categories based on the etiologic agents responsible for disease were used in the analysis. "Bacterial deaths" include decedents whose death certificates mentioned certain ICD-9 codes in the 001004, 008, and 041 groups; "viral deaths" include decedents whose death certificates mentioned certain ICD-9 codes in the 8.6, 045, 047049, 070, 074, 079, 138, and 139 groups; "protozoal deaths" include decedents whose death certificates mentioned certain ICD-9 codes in the 006, 007, and 127 groups; and "other microbial deaths" include decedents whose death certificates mentioned certain ICD-9 codes in the 008, 009, and 139 groups. The category "all enteric disease deaths" includes the sum of the bacterial, viral, protozoal, and other microbial categories.
Each record was examined for the presence of any of the designated ICD-9 codes in any position (from the underlying cause of death through the 20th contributing cause of death) within the record. An indicator variable was indexed for each type of microbe for each diagnosed disease. These cases were then summed within the microbial categories to create national estimates of the number of bacterial, viral, protozoal, and other microbial diseases that contributed to deaths. Each enteric diagnosis was counted separately, so that the number of diseases could be estimated. For example, if an individual died with an intestinal Campylobacter infection (ICD-9 code 8.43) as well as giardiasis (ICD-9 code 7.1) and hepatitis A (ICD-9 code 70.1), the individual would be counted under each of the three enteric diseases rather than as just one decedent with multiple diseases.
The MCD data do not include population figures, so the Census Bureaus Population Estimates Program (14) was used to obtain population denominators for calculation of region-, age-, and race/ethnicity-specific rates. For these analyses, the "White" ethnicity category includes non-Hispanic Whites and the "Black" category includes non-Hispanic Blacks. The "Other" category includes Hispanics and all other reported racial and ethnic designations, including but not limited to Native Americans, Aleuts, Inuits, Pacific Islanders, and Asians.
Age- and race-specific rates of death related to enteric disease were calculated by summing the diseases in each category and then dividing by the corresponding population total. For example, the number of reported bacterial enteric diseases contributing to the deaths of Black children under 5 years of age in 1996 was calculated from the MCD database (number of deaths = 10). This value was then divided by the estimated number of Black children under age 5 years in the United States in 1996 from the US Census data (population = 2,770,999) and multiplied by 100,000 to arrive at a rate of 0.36 deaths due to bacterial enteric diseases per 100,000 population. Thus, the specific death rate for Black children under 5 years of age is 0.36 deaths per 100,000 population (10 deaths x 100,000/2,770,999 population = 0.36 per 100,000).
For each death, the underlying cause and up to 20 contributing causes were analyzed. During the years studied, no decedents had more than 15 causes of death included in their record. The majority of decedents with an enteric disease had either one or two enteric diseases listed as causes of death, and no decedents had more than four enteric diseases listed as causes of death during the study years (table 1).
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RESULTS |
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Rates of reported hepatitis infection and intestinal bacterial infection contributing to death both increased more than threefold over the study period (hepatitis range: from 0.46 reports per 100,000 population in 1989 to 1.68 reports per 100,000 population in 1996, a 363 percent increase; code 008.4 intestinal bacterial infection range: from 0.076 reports per 100,000 population in 1989 to 0.32 reports per 100,000 population in 1996, a 429 percent increase). During that same time, the fraction of all bacterial codes belonging to the ICD-9 code 008.4 increased by 220 percent (from 20 percent of all deaths related to enteric bacterial disease in 1989 to 44 percent in 1996).
Risk factor modeling
Poisson regression analysis was performed for each microbial category separately and then for all enteric infections together. Age group, gender, race, and region were included as categorical predictors, and year was entered into the models as a continuous variable (table 2). In every case, age categories were the most significant predictors of risk, with different age groups being at highest risk for different types of pathogens. Children under age 5 years were at highest risk of death due to other microbial infections (relative risk (RR) = 11.34, 95 percent confidence interval (CI): 10.56, 12.18) and all enteric infections combined (RR = 1.18, 95 percent CI: 1.14, 1.23), while people over age 75 years were at highest risk of death due to bacterial enteric infections (RR = 4.62, 95 percent CI: 4.31, 4.94). Children under age 5 years and infants had the lowest risk of death due to viral enteric pathogens (RR = 0.25, 95 percent CI: 0.23, 0.27) as compared with the 35- to 54-year-old reference group. Risk of death due to protozoal enteric infection was high in both persons aged 524 years (RR = 1.43, 95 percent CI: 0.84, 2.45) and persons aged 2534 years (RR = 2.37, 95 percent CI: 1.77, 3.16), though small numbers of deaths in this microbial category led to imprecise estimates with wide confidence intervals.
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DISCUSSION |
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The steady increase in reports of viral enteric disease as a cause of death in the MCD data could be due to several factors: 1) over time, physicians may be coding more contributing causes of death; 2) the US population is aging, and increasing numbers of aged and immunocompromised Americans are susceptible to viral enteric diseases; and 3) techniques for diagnosing specific enteric viruses have improved since 1989, so it is more likely that decedents could have been diagnosed with viral enteric infections before death and the code was then included as a contributing cause of death. The difference in the rate of increase for viral as opposed to bacterial pathogens supports the hypothesis of changing diagnostic techniques that allow for more detection of viral infections. An analysis of the number of causes of death coded for each record during the years under study indicated that the mean number of causes of death coded was 3.11 per decedent, with a variance between years of 0.0008. This indicates that the number of codes recorded for each decedent was nearly constant over time, and the increased number of reports of enteric disease related to death was not due to a change in the usual number of causes of death coded for each decedent.
Analysis of the underlying cause of death separate from all contributing causes combined revealed that the rate of viral enteric diseases being reported as the underlying cause of death more than doubled during the study period (from 0.48 deaths per 100,000 population in 1989 to 1.20 deaths per 100,000 population in 1996). The rate of reporting of any enteric disease as the underlying cause of death is also increasing and is being driven by the increased reports of viral enteric deaths. Rates of reporting of bacterial and other microbial enteric infections as the underlying cause of death approximately doubled over the study period (bacterial infections: from 0.12 deaths per 100,000 population in 1989 to 0.21 deaths per 100,000 population in 1996; other microbial infections: from 0.11 deaths per 100,000 population in 1989 to 0.21 deaths per 100,000 population in 1996). Bacterial and other enteric microbial deaths represent a small fraction of the deaths related to viral enteric infections.
Determining the true cause behind observed differences in enteric disease burden within population groups or for specific pathogens is beyond the scope of this analysis.
Enteric disease burden in children
Generally, children have high rates of viral infection because they have not yet acquired immunity to viral pathogens. The low reporting rates for viral disease associated with childrens deaths, however, suggest that while children may experience higher rates of enteric viral infection, these infections are rarely so serious as to cause or contribute to death. We estimated that enteric diseases are reported as a contributing cause of death for 456 children under age 5 each year. A review of studies of the impact of diarrhea on childhood morbidity and mortality from 19481986 estimated that 325425 US children under 5 years of age die from diarrhea each year (16). Since different International Classification of Diseases codes were used, our death estimates cannot be directly compared with those of other studies, but our estimates were similar in magnitude to those of the previous review.
Black children under 5 years of age have enteric infections listed as a cause of death more than four times as often as children of other races in the same age group. This suggests that factors other than pathogen virulence are responsible for the greater risk of mortality associated with these infections in some children. Black decedents less than 5 years old had ICD-9 codes for disorders relating to short gestation and low birth weight (ICD-9 codes 765.0 and 765.1) included on their death certificates twice as often as decedents from the White and Other racial categories (Black, 19.5 percent; White, 8.8 percent; Other, 10.9 percent). Other factors and exposures not captured on the death certificate may also contribute to increased risk of death from enteric disease.
Enteric disease in the immunocompromised
The immune status of persons infected with HIV makes them more susceptible to enteric infections and more likely to be suffering from a serious enteric infection at the time of their death. The most interesting trend possibly affecting this subpopulation is the increasing rate of reported viral enteric disease associated with death among people aged 2545 years (figure 2). The rate was fairly linear in 1989, but by 1996 there was a distinct rise in the rates of reported viral enteric disease associated with death. It is possible that this is a direct result of the acquired immunodeficiency syndrome (AIDS) epidemic in those age groups. Peak mortality associated with AIDS occurs among persons aged 3034 years (17).
The rates of reported death associated with protozoal enteric diseases increased similarly in both Blacks and Whites, centered at the 35- to 44-year age group. This finding agrees with current prevalence figures for HIV and AIDS indicating that the age category with both the highest incidence of AIDS and the highest mortality from AIDS is 3034 years in all racial/ethnic groups (17). A similar increase in the rate of reported other enteric microbial infections associated with death is slightly evident among Blacks. This increase may also be due to HIV infection, because the prevalence of HIV infection is higher among minority Americans than in the White population (17).
Impact of enteric disease
In 1996, 0.37 percent of deaths were related to enteric disease (8,589 deaths out of 2,318,212). This is 2.6 times the 1989 value of 0.14 percent. The average percentage increase from one year to the next in the fraction of deaths related to enteric disease from 1989 to 1996 was 116 percent (range, 111122 percent). As the population ages and as more Americans live with compromised immune systems, the fraction of deaths related to enteric disease will continue to increase.
Deaths related to bacterial enteric disease in the elderly, a quickly growing segment of the US population, are increasing at a greater rate than in any other age category. This also suggests that enteric disease will be a continuing and expanding burden on the health care system unless better prevention and control measures are found and implemented. The fact that hepatitis A, a vaccine-preventable disease, is contributing to the deaths of more people each year should not go unnoticed. Vaccination against hepatitis A may be one public health intervention strategy for reducing preventable deaths.
Another factor affecting the number of deaths related to enteric disease each year is the number of Americans living with HIV infection (ICD-9 code 042). Of the deaths related to enteric disease in 1989, 3.3 percent also included HIV as a cause of death (161 deaths out of 4,912); by 1996, this fraction had increased to 4.6 percent (592 deaths out of 12,906).
In summary, the rate of reporting of enteric diseases as contributing causes of death more than doubled between 1989 and 1996. People over age 65 years have the highest rates of reporting of enteric diseases as causes of death. Viral enteric diseases contributed to an increasing number of deaths among people in the 35- to 55-year age groups during the study period, probably because of the impact of HIV and AIDS in that population. Nonwhite Americans are most affected by enteric diseases as contributing causes of death. While enteric disease caused many fewer deaths in the 1990s than in the 1920s, these diseases remain an important and often preventable contributor to mortality in the United States.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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