[Emerging Infectious Diseases] [Volume 4 No. 4 /October-December 1998] Dispatches Increasing Hospitalization and Death Possibly Due to Clostridium difficile Diarrheal Disease Floyd Frost,* Gunther F. Craun,† and Rebecca L. Calderon‡ *Southwest Center for Managed Care Research, Albuquerque, New Mexico, USA; †Gunther F. Craun and Associates, Staunton, Virginia, USA; and ‡U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA --------------------------------------------------------------------------- This study calculated yearly estimated national hospital discharge (1985 to 1994) and age-adjusted death rates (1980 to 1992) due to bacterial, viral, protozoal, and ill-defined enteric pathogens. Infant and young child hospitalization (but not death) rates in each category increased more than 50% during 1990 to 1994. Age-adjusted death and hospitalization rates due to enteric bacterial infections and hospitalizations due to enteric viral infections have increased since 1988. The increases in hospitalization and death rates from enteric bacterial infections were due to a more than eightfold increase in rates for specified enteric bacterial infections that were uncoded during this period (ICD9 00849). To identify bacterial agents responsible for most of these infections, hospital discharges and outpatient claims (coded with more detail after 1992) were examined for New Mexico's Lovelace Health Systems for 1993 to 1996. Of diseases due to uncoded enteric pathogens, 73% were due to Clostridium difficile infection. Also, 88% of Washington State death certificates (1985 to 1996) coded to unspecified enteric pathogen infections (ICD0084) listed C. difficile infection. Infectious diarrhea remains a major cause of death worldwide (1). In the United States, enteric pathogens are estimated to cause 25 to 99 million episodes of diarrhea and vomiting each year, resulting in 2.2 million physician visits (2). U.S. residents at highest risk for severe illness or death from diarrhea are young children (3-5) and the elderly (5). Race, socioeconomic status, and residence in a nursing home are also risk factors for death due to diarrhea (1-6). Increasing concern over waterborne Table 1. International Classification transmission of enteric pathogens of Disease (ICD9) (7-10) prompted this study. Since hospitalization or death from infectious diarrhea is uncommon, ------------------------------------- state- or hospital-specific studies Categories are unlikely to include enough cases to accurately estimate the incidence or describe the temporal ------------------------------------- trends in hospitalization or death Bacterial rates. Therefore, this study focused on national hospitalization 001(sup a)Cholera and death data to determine if the incidence of hospitalizations or 002(sup a)Typhoid and paratyphoid deaths due to infectious diarrhea fevers has changed during the past decade 003(sup a)Other salmonella infections and, if so, to identify specific pathogens responsible for the 004(sup a)Shigellosis changes. 005(sup a)Other food poisoning Data Sources bacterial Computerized data on U.S. death 008(sup a)Intestinal infections due to rates (1980 to 1992), which other organisms included coded underlying cause of death, and National Hospital 0080 Escherichia coli Discharge Survey (NHDS) data (1985 to 1994) were obtained from the 0081 Arizona group of paracolon National Center for Health bacilli Statistics (NCHS). NHDS data came 0082 Aerobacter aerogenes from yearly surveys of hospital (Enterobacter) discharges conducted by NCHS 0083 Proteus through a multistage sampling scheme (11). Yearly national 0084 Other specified bacteria estimates of discharges by diagnosis, age, and gender were 0085 Bacterial enteritis obtained by using multipliers (unspecified) provided by NCHS. Yearly midyear 041(sup a)Bacterial infection in Bureau of the Census population conditions classified estimates were used for calculating elsewhere and of unspecified national death and hospitalization site rates. For hospital coding Deaths Due to Diarrhea, 1980–1992 00841 Staphylococcus The number of diarrhea deaths in 00842 Pseudomonas 1980 to 1992 was determined by using the coded underlying causes 00849 Other of death. Deaths are coded to only four digits of the International After 1992 Classification of Disease 9th revision (ICD9). Causes of death 00843 Campylobacter were grouped into four categories 00844 Yersinia enterocolitica according to type of pathogen: bacterial, parasitic, viral, and 00845 Clostridium difficile ill-defined (Table 1). 00846 Other anaerobes Hospitalizations Due to Diarrhea, 1985–1994 00847 Other gram-negative bacteria Hospitalizations due to diarrhea Viral (coded to five digits of the ICD9) were ascertained for each year from 074(sup a)Specified disease due to 1985 to 1994 by selecting the same coxsackie virus groups of ICD9 codes from the first 045(sup a)Acute poliomyelitis seven discharge diagnoses recorded for each hospital discharge. For 047(sup a)Meningitis due to the few hospital discharges with enterovirus multiple infectious diarrhea codes, priority was given to the code that 048 Other enterovirus diseases appeared first. of central nervous system Hospitalization and Death Rates 0086 Enteritis due to specified Adjusted by Age virus 0088 Other viral organism not Age-adjusted hospitalization and elsewhere classified death rates for each year, standardized to the 1990 U.S. 0700(sup a)Viral hepatitis A with population, were calculated for hepatic coma each of the four ICD9 enteric 0701(sup a)Viral hepatitis A without pathogen categories (bacterial, mention of hepatic coma parasitic, viral, and ill-defined). A ratio of deaths to Parasitic hospitalizations for each category was calculated by dividing the number of deaths caused by 006(sup a)Amebiasis pathogens in each category by the number of hospital discharges with 007(sup a)Other protozoal intestinal the first infectious enteric diseases disease discharge diagnosis 127(sup a)Other intestinal included in that category. helminthiases 128 Other and unspecified Hospitalizations and Deaths helminthiases Bacterial Causes 129(sup a)Intestinal parasitism, unspecified Hospitalizations and deaths due to bacterial causes (including Other cholera, typhoid and paratyphoid fever, other salmonella infections, 009(sup a)Ill-defined intestinal shigellosis, other food poisoning infections bacteria, and infections due to ------------------------------------- other specified bacteria) were also (sup a)Diarrhea codes selected for study. analyzed (Table 1). Age-adjusted death rates (each year) from "other specified enteric bacteria" (ICD9 0084) and age-adjusted hospitalization rates (each year) due to "uncoded but specified enteric bacteria" (ICD9 00849) were calculated. Additional cause codes were added in 1992 (ICD9 00843-00847 for hospital ICD coding, including 00845 for Clostridium difficile (Table 1). However, these codes were not yet incorporated for this analysis of national hospital discharge data. During this time, cause of death was only coded to the fourth ICD9 digit. Deaths (1985–1996) and Hospitalizations (1993–1996) To make use of enhanced ICD9 coding available after 1992, inpatient health-care records for 1993 to 1996 from the Lovelace Health Systems in Albuquerque, New Mexico, were reviewed to identify bacterial pathogens responsible for most hospitalizations that would have been coded (before 1992) to specified but uncoded bacterial pathogens. Since death records are only coded to the fourth digit, Washington State deaths (with any multiple cause of death code of ICD9 0084) occurring between 1985 and 1996 were also reviewed to identify the specific pathogen that resulted in this ICD9 code assignment. Findings Death Rates Age-adjusted death rates for protozoal, viral, and other causes remained relatively stable from 1980 to 1992 (Figure 1), but age-adjusted death rates for bacterial causes increased from 0.060 per 100,000 population [Figure 1.] Age-adjusted in 1980 to 0.104 per 100,000 in 1994, more death rates per 100,000 than 60% (p < 0.00001) (Figure 1). To population by grouped ascertain the specific bacterial agents underlying cause of death responsible for the increase, deaths were for selected enteric initially categorized by each three- and pathogens, United States four-digit ICD9 code included in the 1985-94. (Standardized to bacterial category. the 1970 U.S. population). The age-adjusted death rate due to other specified bacterial pathogens (ICD9 0080-0084) increased from 0.0102 per 100,000 population to 0.0821 per 100,000 population (p < 0.000001), more than eightfold (Table 2). This increase accounted for the overall increase in the age-adjusted death rate for deaths due to enteric bacterial pathogens, as the age-adjusted death rate for other enteric bacterial causes remained stable or declined. Most of the increase in the age-adjusted death rate for ICD9 0080-0084 was due to a statistically significant (p < 0.00001) increase in the death rate of persons age 45 years and older (Table 2). For both older and younger age groups, the increase was most apparent from 1988 to 1992. During this time, approximately 96% of U.S. deaths coded to ICD9 0080-0084 were coded to ICD9 0084, which includes other specified but uncoded enteric bacterial pathogens. Table 2. Age-adjusted death rates for bacterial causes of diarrhea ------------------------------------------------------------------------------------------- ICD9 0080-0084(sup a) Remainder of bacterial causes(sup b) ----------------------------------- --------------------------------------------- <45 >45 >45 >45 Year AARATE(sup c)yrs(sup d) yrs(sup d)(Deaths) AARATE(sup 3) yrs(sup d) yrs(sup d)(Deaths) ------------------------------------------------------------------------------------------- 1980 0.0102 0.0013 0.0090 ( 21) 0.0500 0.0133 0.0368 (107) 1981 0.0135 0.0035 0.0100 ( 29) 0.0559 0.0107 0.0453 (120) 1982 0.0107 0.0022 0.0085 ( 23) 0.0463 0.0087 0.0365 (100) 1983 0.0144 0.0040 0.0104 ( 32) 0.0426 0.0092 0.0334 ( 94) 1984 0.0101 0.0026 0.0075 ( 23) 0.0433 0.0068 0.0365 ( 98) 1985 0.0092 0.0016 0.0075 ( 21) 0.0587 0.0131 0.0456 (135) 1986 0.0119 0.0029 0.0090 ( 28) 0.0485 0.0108 0.0347 (105) 1987 0.0175 0.0029 0.0146 ( 41) 0.0506 0.0097 0.0409 (120) 1988 0.0241 0.0008 0.0232 ( 57) 0.0305 0.0071 0.0234 ( 74) 1989 0.0342 0.0016 0.0326 ( 83) 0.0465 0.0111 0.0354 (114) 1990 0.0520 0.0043 0.0478 (129) 0.0374 0.0070 0.0303 ( 93) 1991 0.0547 0.0027 0.0520 (139) 0.0254 0.0055 0.0190 ( 65) 1992 0.0821 0.0046 0.0775 (213) 0.0220 0.0049 0.0171 ( 57) ------------------------------------------------------------------------------------------- (sup a) Causes include Escherichia coli (0080), Arizona group (0081), Aerobacter aerogenes (Enterobacter) (0082), Proteus mirabilus and morganii (0083), other specified enteric bacterial infections (0084). (sup b) Causes include cholera (001), typhoid and paratyphoid fever (002),other salmonella infections (003), shigellosis (004), bacterial enteritis, unspecified (0085), bacterial infection in conditions classified elsewhere (041). (sup c) Age-adjusted death rates per 100,000 population, adjusted to the 1990 U.S. population. (sup d) Contribution to age-adjusted death rate from persons younger than age 45 years and from persons age 45 years and older. Hospitalization Rates The estimated number of hospitalizations in the United States coded to infectious enteric agents increased from 131,252 to 337,178 from 1985 to 1994, a 2.5-fold increase. Age-adjusted hospitalization rates for viral [Figure 2.] Age-adjusted causes increased more than twofold, whereas hospital discharge rates rates for bacterial causes increased more per 100,000 population by than fourfold (Figure 2). Hospitalization grouped discharge diagnosis rates for protozoal and ill-defined causes for selected enteric remained stable or fluctuated from year to pathogens, United States year (Figure 2). In 1985, bacterial causes 1980-92. (Standardized to accounted for 21% of all hospitalizations for the 1970 U.S. population). infectious enteric agents, while in 1994, Discharges were included if they accounted for 38% (Figure 2). A large a selected enteric pathogen increase was apparent in the age-adjusted was among the first seven hospitalization rate for other specified discharge diagnoses. The bacterial pathogens (ICD9 00800-00849) pathogen group was assigned (Figure 2). according to the first pathogen listed. The increased age-adjusted rate of hospital discharge coded to "other specified bacterial pathogen" infections (ICD9 0080-00849) was statistically significant (p < 0.00001) (Table 3). The age-adjusted hospitalization rate for bacterial causes, other than ICD9 0080-00849, remained stable (Table 3). As with deaths, the increase in hospitalizations for bacterial causes appears to have begun in 1988, but unlike the increase in death rates, hospitalization rates increased for persons both younger and older than 45 years of age (p < 0.001) (Table 3). For discharges coded to ICD9 0080-00849, 88% were coded to ICD9 00849, which includes "other uncoded but specified enteric bacterial pathogens." Discharge rates due to bacterial causes of diarrhea increased in each age group, with greater increases seen in children and persons more than 45 years of age (Table 4). Infant hospitalization rates increased for bacterial, viral, protozoal, and ill-defined conditions (p < 0.001) (Table 4). Hospitalization rates also increased for children ages 1 to 4 years of age for bacterial, viral, and ill-defined conditions (p < 0.001) (Table 4); however, no increases in children's death rates were observed. Table 3. Age-adjusted hospitalization rates for bacterial causes of diarrhea --------------------------------------------------------------------------------------------- ICD9 0080-0084(sup a) Remainder of bacterial causes(sup b) ------------------------------------ ----------------------------------------- <45 >45 (Dis- <45 >45 (Dis- Year AARATE(sup c) yrs(sup d) yrs(sup d) charges) AARATE(sup c) yrs(sup d) yrs(sup d)charges) --------------------------------------------------------------------------------------------- 1985 3.72 1.71 2.02 ( 8,716) 7.76 4.06 3.70 (18,286) 1986 4.79 2.01 2.74 (11,316) 5.56 2.60 2.96 (13,174) 1987 6.05 1.95 4.10 (14,433) 4.55 2.14 2.41 (11,037) 1988 11.36 3.20 8.14 (27,492) 9.07 6.04 3.02 (22,219) 1989 16.09 5.64 11.05 (38,894) 8.10 4.96 3.14 (19,931) 1990 25.23 6.40 18.82 (62,750) 8.28 4.29 4.00 (21,037) 1991 30.67 7.55 23.12 (78,100) 6.05 3.52 2.53 (15,620) 1992 41.96 9.71 32.25 (107,874) 5.56 3.15 2.42 (14,568) 1993 33.91 8.32 25.60 (88,715) 5.51 3.54 1.98 (14,454) 1994 42.66 10.48 30.18 (113,411) 5.22 3.44 1.78 (13,944) ----------------------------------------------------------------------------------------------- (sup a)Causes include Escherichia coli (0080), Arizona group (0081), Aerobacter aerogenes (Enterobacter) (0082), Proteus mirabilus and morganii (0083), Staphylococcus (00841), Pseudomonas (00842), Campylobacter (00843), Yersinia enterocolitica (00844), Clostridium difficile (00845), other anaerobes (00846), other gram-negative (00847), other (00849). Codes 00843-00847 were added in 1992. (sup b)Causes include cholera (001), typhoid and paratyphoid fever (002), other salmonella infections (003), shigellosis (004), bacterial enteritis, unspecified (0085), bacterial infection in conditions classified elsewhere (041). (sup c)Age-adjusted discharge rates per 100,000 population, adjusted to the 1990 U.S. population. (sup d)Contribution to age-adjusted discharge rate from persons younger than age 45 years and from persons age 45 years and older. Death-to-Discharge Ratio The ratio of deaths to hospitalizations for protozoal and ill-defined causes of diarrhea remained stable between 1985 and 1992. However, despite the increasing incidence of enteric bacteria-caused deaths, the ratio of deaths to hospitalizations declined from 6.6 per 1,000 to 2.7 per 1,000 hospitalizations (p < 0.001). The ratio of hospitalizations to deaths in the viral cause category declined from 6.0 per 1,000 to 2.9 per 1,000 hospitalizations (p < 0.001). Clostridium difficile Infections Additional disease codes for hospital discharge coding were Table 4. Age-specific rates of added in 1992, reducing the number hospitalizations (estimated of discharges coded to ICD9 00849. discharges) by diagnostic group Examination of all computerized health-care billing records (1993 -------------------------------------- to 1996) with an ICD9 of 00843-00849 from the Lovelace Discharge rate/100,000 Hospital and Lovelace Health Care population (discharges) Systems in Albuquerque, New Mexico, found 94 inpatients with these codes; C. difficile (ICD9 00845) ------------------------------ accounted for 73%. This suggests that C. difficile infection was Age 1985-89 1990-94 likely to have been the most common pathogen previously coded to ICD9 -------------------------------------- 00849. Eighty-six percent of Bacterial causes(sup a) patients diagnosed with C. difficile were younger than age 60 with 65% younger than age 40. In addition, the records of 22 (88%) 1 57.5 (10,374) 100.8 (19,536) of 25 Washington State deaths occurring between 1985 and 1996 1-4 7.5 ( 5,416) 21.5 ( 16,696) with a multiple cause of death code 5-14 4.6 ( 7,988) 8.2 ( 14,988) ICD9 0084 cited C. difficile. 15-24 7.6 (14,739) 10.6 ( 19,216) Conclusions 25-34 13.0 (26,955) 13.5 ( 28,583) Infectious diarrhea remains an 35-44 10.1 (17,089) 18.5 ( 36,871) uncommon cause of hospitalization and accounted for almost the same 45-54 11.1 (13,551) 26.4 ( 36,152) number of deaths in 1992 as in 55-64 18.1 (19,302) 41.7 ( 43,774) 1980. Increases in death rates for bacterial causes offset stable or 65-74 34.9 (30,182) 95.4 ( 87,902) declining death rates for viral, parasitic, and ill-defined causes 75 65.9 (39,903) 211.8(145,965) of diarrhea. The increase in death rates for "other specified enteric Protozoal causes(sup b) bacteria" was due to increases in deaths associated with ICD9 code 0084, "uncoded but specified 1 3.8 ( 680) 9.1 ( 1,767) bacterial pathogens." Increases in 1-4 3.0 (2,157) 2.6 ( 2,006) hospitalization rates for these "uncoded but specified bacterial 5-14 1.4 (2,508) 1.3 ( 2,426) pathogens" correspond temporally to 15-24 3.3 (6,337) 1.8 ( 3,228) the increase in death rates coded to ICD9 0084. A review of recent 25-34 4.3 (8,934) 5.6 (11,941) hospitalization records from a New 35-44 5.7 (9,723) 5.0 (10,044) Mexico health maintenance organization and death records from 45-54 4.8 (5,902) 2.8 ( 3,894) Washington State show that C. 55-64 4.5 (4,786) 3.4 ( 3,611) difficile was the most common pathogen in this coding group. 65-74 9.0 (7,783) 5.0 ( 4,640) These findings suggest that C. difficile was likely to have been 75 12.4 (7,507) 6.6 ( 4,561) responsible for the increase in and death rates from enteric both age-adjusted hospitalization Viral causes(sup c) bacterial pathogens. 1 167.6 (30,234) 387.7 (75,120) Increases in death and 1-4 8.9 ( 6,400) 67.1 (52,021) hospitalization rates due to bacterial causes may simply 5-14 8.3 (14,566) 16.3 (29,617) indicate improved ICD9 coding for both hospitalization and death or 15-24 10.4 (20,142) 13.5 (24,577) increased diagnostic accuracy. New 25-34 15.3 (31,694) 17.4 (36,913) kits for detection of C. difficile toxins in stool samples may have 35-44 8.8 (14,837) 11.4 (22,707) resulted in increased C. difficile 45-54 6.7 ( 8,209) 8.3 (11,312) diagnoses. If so, the increase in enteric bacterial infections, 55-64 10.6 (11,231) 5.4 ( 5,658) likely due to C. difficile, may not 65-74 10.4 ( 9,020) 8.1 ( 7,481) be a true increase in illness from this pathogen. If this were the 75 18.8 (11,390) 15.8 (10,893) case, however, one might predict a corresponding reduction in Ill-defined diarrheal causes(sup d) hospitalizations and deaths from ill-defined diarrheal causes. Death rates for ill-defined causes of 1 178.9 (32,272) 283.9 (55,006) diarrhea presumed to be infectious actually rose somewhat during 1990 1-4 27.0 (19,452) 62.8 (48,694) to 1992, and hospitalization rates 5-14 13.3 (23,301) 17.3 (31,594) have remained stable. Further studies are needed to determine if 15-24 24.4 (47,242) 18.2 (32,966) this increased age-adjusted 25-34 30.3 (62,701) 21.7 (45,966) hospitalization and death rate is due to increased C. 35-44 25.7 (43,618) 19.4 (38,516) difficile–associated disease and, 45-54 29.5 (35,972) 28.9 (39,459) if so, to identify risk factors for infection and disease. 55-64 46.8 (49,773) 32.6 (34,245) Additional information about the 65-75 75.5 (65,336) 50.2 (46,257) causes of increased hospitalization 75 114.7 (69,476) 93.1 (64,163) and death from enteric bacterial pathogens could be provided by a -------------------------------------- review of computerized health-care delivery records. C. difficile can (sup d)Discharges with an enteric bacteria be associated with almost any diagnosis (ICD9 001-005, 0080-0085, antibiotic therapy, but it has been 041). particularly associated with (sup b)Discharges with an enteric parasite aminopenicillins, cephalosporins, diagnosis (ICD9 006-007, 127, 129). and clindamycin, which have greater (sup c)Discharges with an enteric virus effects on the intestinal flora diagnosis (ICD9 0086, 0088, 045, 047, (12). Other factors trigger C. 048, 0700, 0701, 074). difficile toxinassociated colitis (13). Records from health maintenance organizations containing prior diagnoses and pharmaceutical treatments may provide better understanding of the risk factors. In this study, data from one hospital system in one state and deaths occurring in one state suggest that a likely cause of the national increase in hospitalizations and deaths due to enteric bacteria may be C. difficile infection. It is possible that C. difficile is a relatively more important cause of hospitalization at Lovelace Health Systems in New Mexico and of death in Washington State than elsewhere in the United States. The age-specific rates of hospital discharge coded to enteric bacterial, viral, and ill-defined conditions increased for children under 5 years of age. Reasons for these increases merit further inquiry. No increases in death rates from these pathogens were observed in these age groups. However, since adverse outcomes of infectious diarrhea that requires hospitalization may indicate problems with access to health care, information on the socioeconomic characteristics of the families of these children would be of interest. Dr. Frost is an epidemiologist and the director of the Southwest Center for Managed Care Research in Albuquerque, New Mexico. His research interests include the study of waterborne diseases and the use of health-care data for promoting public health programs within managed care organizations. Address for correspondence: Floyd Frost, Southwest Center for Managed Care Research, 2425 Ridgecrest Drive, S.E., Albuquerque, NM 87108, USA; fax: 505-262-7598; e-mail: ffrost@lrri.org. References 1. Murray CJL, Lopex AD. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. Geneva: World Health Organization; 1996. 2. Garthright WE, Archer DI, Kvenberg JE. Estimates of incidence and cost of intestinal infectious diseases in the United States. Public Health Rep 1988;103:107-15. 3. Gibson JJ, Alexander GR. Correlates of infant death from infectious diarrhea in the southeastern United States. South Med J 1985;78:26-30. 4. Mel-Shang H, Glass RI, Pinsky PF, Young-Okoh N, Sappenfield WM, Buehler JW, et al. Diarrhea deaths in American children: are they preventable? JAMA 1988;260:3281-5. 5. Lew JF, Glass RI, Gangarosa RE, Cohen IP, Bern C, Moe CL. Diarrhea deaths in the United States, 1979 through 1987. JAMA 1991;265:3280-4. 6. Cheney CP, Wong RKH. Acute infectious diarrhea. Gastrointestinal Emergencies 1993;77:1169-90. 7. Moore AC, Herwaldt BL, Craun FG, Calderon RL, Highsmith AK, Juranek DD. Surveillance for waterborne disease outbreaks—United States 1991-92. MMWR CDC Surveill Summ 1993;42(5):1-22. 8. Calderon RL, Johnson CC, Craun GF, Dufour AP, Karlin RK, Sinks T, et al. Health risks from contaminated water: do class and race matter? Toxicol Ind Health 1993;9:879-900. 9. Kramer MH, Herwaldt BL, Craun GF, Calderon RL, Juranek DD. Surveillance for waterborne-disease outbreaks—United States 1993-94. MMWR CDC Surveill Summ 1996;45:1-33. 10. Solo-Gabriele H, Neumeister S. U.S. outbreaks of cryptosporidiosis. Journal of the American Water Works Association 1996;(Sept):76-84. 11. Simmons WR. Development of the design of the NCHS hospital discharge survey. Vital Health Statistics 1970;2(39). 12. Job ML, Jacobs NF. Drug-induced Clostridium difficile-associated disease. Drug Saf 1997:17:37-46. 13. Caputo GM, Weitekamp MR, Bacon AE, Whitener C. Clostridium difficile infection: a common clinical problems for the general internist. J Gen Intern Med 1994;9(9):528-33. Emerging Infectious Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA Please note that figures and equations are not available in ASCII format; their placement within the text is noted by [fig] and [eq], respectively. Greek symbols are spelled out. The following codes are used: (ft) for footnote; (sup) for superscript; (sub) for subscript; >/= for greater than or equal to. URL: ftp://ftp.cdc.gov/pub/EID/vol4no4/ascii/frost.txt