Emerging Infectious Diseases [Volume 5 No.5 / September - October 1999] Letters A Case of Corynebacterium pseudodiphtheriticum Nosocomial Pneumonia To the Editor: Corynebacterium pseudodiphtheriticum has seldom been isolated from patients with upper respiratory tract infections and pneumonia. Most reported infections are community acquired and occur in patients with underlying disease and immunosuppression (1). We report a case characterized by hospital-acquired pneumonia in a debilitated patient. Review of the literature indicates that C. pseudodiphtheriticum should be regarded an emerging pathogen. On April 1, 1998, a 68-year-old woman was admitted to the intensive care unit for acute respiratory distress. She had a 14-month history of amyotrophic lateral sclerosis. Three weeks before admission, she had been hospitalized for Staphylococcus aureus pneumonia and had recovered after treatment with amoxicillin and clavulanic acid plus ciprofloxacin. At the time of admission, the patient had a temperature of 38°C. Systolic blood pressure was 120 mm Hg. Ventilation was spontaneous, with respirations 24 per minute; pulmonary sibilants were noted. Respiratory acidosis was also identified, with a pH of 7.35, SaO2 92%, PaO2 60 mm Hg, and PaCO2 60 mm Hg. Laboratory data included 18,000 leukocytes per ml (90% polymorphonuclear cells) and a serum fibrin level of 7 g/L. A chest X-ray showed pneumopathy of the lower segment of the right lung, which was compatible with the diagnosis of inhalation pneumopathy. On day 2 of admission, the patient's temperature was 39°C, and she had paresis of the vocal cords. After C. pseudodiphtheriticum infection was diagnosed, treatment with intravenous cloxacillin (l g 3 times/day) and amoxicillin plus clavulanic acid (l g 3 times/day) was started. On day 3 after admission, the patient's breathing worsened, a radiograph showed bilateral pneumopathy, and she was intubated for mechanical ventilation. Two days later, her breathing improved, and a second bronchic aspiration was sterile. The patient eventually died of unrelated complications. Direct microscopy examination of a Gram-stained bronchial aspiration sample showed numerous polymorphonuclear cells and gram-positive bacilli in parallel rows, which did not show pleomorphism. After 48 hours of incubation at 37°C, 10(sup 6) colony-forming units/ml of a coryneform bacillus further identified as C. pseudodiphtheriticum grew in pure culture on blood agar gelose (BioMérieux, La Balme les Grottes, France) under a 5% CO2 atmosphere and did not produce hemolysis. The test for catalase was positive, and the following biochemical characteristics were obtained by using a commercial identification strip (ApiCoryne, BioMérieux): absence of carbohydrate fermentation, urea hydrolysis, and nitrate reduction compatible with C. pseudodiphtheriticum. Minimum inhibitory concentrations (disk diffusion method) were 2 mg/L for amoxicillin, 2 mg/L for cefalotin, 0.09 mg/L for doxycycline, 0.03 mg/L for gentamicin, <4 mg/L for vancomycin, 16 mg/L for erythromycin, and 20 mg/L for trimethoprim-sulfamethoxazole. Identification was confirmed by analysis of the cell-wall fatty acid profile by the Sherlock system, by the trypticase soy broth agar database 3.9 (MIDI Inc., Newark, DE), and by 16S rRNA sequence analysis under previously described conditions (2). The 16S rRNA gene sequence was compared with all eubacterial 16S rRNA sequences available in the GenBank database by using the multisequence comparison Advanced Blast NCBI. The sequence had a 99% similarity to that of C. pseudodiphtheriticum (1039/1047 base pairs). Eighty-nine cases of infection possibly caused by C. pseudodiphtheriticum have been identified in the last 57 years. Of these, 57 (62.9%) were upper respiratory infections, which included rhinosinusitis, tracheitis, tracheobronchitis, and bronchitis; 19 (21.3%) were pneumonia (3-7). Ten (11.2%) cases of endocarditis were reported (8); there was also one case each of urinary tract malakoplakia after renal transplantation (9), lung abcess (10), diskitis (11), and lymphadenitis (12). Unlike C. diphtheriae, C. pseudodiphtheriticum is a commensal bacterium that does not produce toxins and needs predisposing factors to become a pathogen causing pneumonia. Of patients with hospital-acquired C. pseudodiphtheriticum upper respiratory tract infections and pneumonia (7 of 26 upper respiratory tract infections and 2 of 14 cases of pneumonia reported in the early 1990s), all had underlying pathologic features. Predisposing factors were as follows: 33.7% had lung and tracheobronchial diseases, including chronic obstructive pulmonary disease, angina (5), chronic emphysema, asthma, and bronchitis (6); 32.5% had congestive heart failure (5). Of those with immunodepression, 5% had AIDS, 7.2% had undergone chemotherapy or prolonged steroid use; and 18.2% had other pathologic features, disseminated intravascular coagulation (6), chronic renal failure, diabetes mellitus (5), and connective tissue disease (5,6). The first source of pneumonia is usually inhalation, as was the case for our patient, who had paresis of the vocal cords. She was not immunosuppressed but was debilitated by amyotrophic lateral sclerosis. The second factor is often an endotracheal intubation, as reported in a previously healthy 29-year-old trauma victim who contracted pneumonia due to C. pseudodiphtheriticum after 7 days of intubation (7). An increase in cases reported from 1932 to 1998 indicates the emergence of infections due to C. pseudodiphtheriticum. Thirty-four cases were reported from 1932 to 1989 (57 years), and 55 cases were reported from 1990 to 1998 (8 years). Reasons for the emergence of C. pseudodiphtheriticum infections may include confusion between C. diphtheriae and C. pseudodiphtheriticum infections. For example, two cases of C. pseudodiphtheriticum exudative upper respiratory tract infections with a pseudomembrane were first diagnosed as respiratory diphtheria. In the first case, C. pseudodiphtheriticum was isolated from a 32-year-old Uzbek man who had a severe sore throat and dysphagia lasting 2 days (3). In a second case, a 4-year-old girl had exudative pharyngitis with a pseudomembrane, which was possibly caused by C. pseudodiphtheriticum (4). The availability of commercial strips for the identification of C. pseudodiphtheriticum and 16S rRNA sequencing eliminates such confusion. Cécile Martaresche, Pierre-Edouard Fournier, Véronique Jacomo, Marc Gainnier, Alain Boussuge, and Michel Drancourt Hôpital Salvator, Assistance Publique-Hôpitaux de Marseille, Marseille, France References 1. Brown AE. Other Corynebacteria and Rhodococcus. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995. p. 1874. 2. Weisburg WC, Barns SM, Pelletier DA, Lane DJ. 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol 1991;173:697-703. 3. Santos MR, Ghandi S, Vogler M, Hanna BA, Holzman RS. Suspected diphtheria in a Uzbek national; isolation of C. pseudodiphtheriticum resulted in a false positive presumptive diagnosis. Clin Infect Dis 1996;22:735. 4. Izurieta HS, Strebel PM, Youngblood T, Hollis DG, Popovic T. Exudative pharyngitidis possibly due to C. pseudodiphtheriticum, a new challenge in the differential diagnosis of diphtheria. Emerg Infect Dis 1997;3:65-8. 5. Manzella JP, Kellog JA, Parsey KS. Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen in adults. Clin Infect Dis 1995;20:37-40. 6. Ahmed K, Kawakami K. Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen. Clin Infect Dis 1995;20:41-6. 7. Miller RA, Rompalo A, Coyle MB. Corynebacterium pseudodiphtheriticum pneumonia in an immunologically intact host. Diagn Microbiol Infect Dis 1986;4:165-71. 8. Wilson ME, Shapiro DS. Native valve endocarditis due to Corynebacterium pseudodiphtheriticum. Clin Infect Dis 1992;15:1059-60. 9. Nathan AW, Turner DR, Aubrey C, Cameron JS, Williams DJ, Ogg CS, et al. Corynebacterium hofmannii infection after renal transplantation. Clin Nephrol 1982;17:315-8. 10. Andavolu RH, Venkita J, Lue Y, McLean T. Lung abscess involving Corynebacterium pseudodiphtheriticum in a patient with AIDS-related complex. New York State Journal of Medicine 1986;86:594-6. 11. Wright ED, Richards AJ, Edje AJ. Discitis caused by Corynebacterium pseudodiphtheriticum following ear, nose and throat surgery. Br J Rheumatol 1995;34:585-6. 12. LaRocco M, Robinson C, Robinson A. Corynebacterium pseudodiphtheriticum associated with suppurative lymphadenitis. European Journal of Clinical Microbiology 1987;6:79. Family Outbreak of Rickettsia conorii Infection To the Editor: Over a 15-day period, three young siblings were separately taken to an emergency room in Israel, with symptoms suggesting a contagious viral illness (fever, maculopapular rash, hepatosplenomegaly, lymphadenopathy, neutropenia, and thrombocytopenia). None of the children had been in direct contact with animals. Specific immunoglobulin (IgM) immunofluorescence assay (IFA) 7 to 8 days after admission of each child confirmed the diagnosis of Rickettsia conorii infection. Spotted fever is the generic name given to a variety of tickborne rickettsial diseases distributed worldwide. In Mediterranean countries, including Israel, spotted fever is caused by members of the R. conorii complex. Spotted fever has been endemic in Israel for more than 40 years, with several hundred cases reported annually. In 1997, two fatal cases were reported (1). Spotted fever is caused by a variant member of R. conorii, which is transmitted by the dog tick Rhipicephalus sanguineous (2,3). The disease has a broad spectrum of clinical signs, from asymptomatic to fatal (4,5). Symptoms and signs include fever, headache, vomiting, myalgia, conjunctivitis, and a typical maculopapular or purpuric rash. The tache noir at the site of the tick bite, which is found in patients in Europe, is seldom, if ever, seen in Israel. The first patient, a 6-year-old boy, was taken to the pediatric emergency room with high fever and a diffuse rash, approximately 1 week after visiting a cousin who had similar complaints. Physical examination showed temperature of 40°C, chills, diffuse maculopapular rash all over the body, including the hands and feet, hepatosplenomegaly, and lymphadenopathy. Blood tests showed neutropenia, thrombocytopenia, and hyponatremia. Because Rickettsia was included in the differential diagnosis, immunofluorescent assay (IFA) for Rickettsia was performed and intravenous doxycycline (2 mg/kg/day) was initiated. One week later, the boy's 8-month-old sister was brought to the emergency room with similar complaints, and 2 days afterwards his 2-year-old sister began to have the same symptoms. A detailed history revealed that all children had played on a lawn frequented by dogs. All three siblings had fever, chills, and diffuse maculopapular rash all over the body, including the hands and feet. An IgM IFA test for R. conorii from the first child was negative on the day of admission and became positive 8 days later. On the day of the boy's hospital discharge, his 8-month-old sister was taken to the emergency room. Her serology test was negative on admission but became positive 7 days later. The third (2-year-old) sibling's first blood test was negative, and the family did not agree to a second blood test. All three children responded well to doxycycline (2 mg/kg/day, with a double dose the first day) for 5 to 7 days. Most symptoms subsided within 48 hours. Spotted fever is usually a sporadic illness and is not spread from person to person. Clusters of cases have been reported. Yagupsky reported spotted fever in Israel in a few children living near each other in an agricultural settlement (6). A report from the Delaware Division of Public Health described a group of children who had been camping together where contact with ticks was likely (7). This case illustrates that spotted fever may be acquired even without direct contact with animals, through exposure to ticks in places frequented by infected animals. Our report suggests that Rickettsial illness should be considered in the differential diagnosis of fever with rash in disease-endemic areas, even if the timing of similar complaints in several family members suggests a contagious viral illness. G. Shazberg, J. Moise, N. Terespolsky, and H. Hurvitz Bikur Cholim General Hospital, Jerusalem, Israel References 1. Spotted fever. Jerusalem, Israel: Ministry of Health, Department of Epidemiology; 1997. 2. Goldwasser RA, Steiman Y, Klinberg W, Swartz TA, YJingberg MA. The isolation of strains of Rickettsiae of the spotted fever group in Israel and their differentiation from other members of the group by immunofluorescence methods. Scand J Infect Dis 1974;6:53-62. 3. Manor E, Ighbarieh J, Sarov B, Kassis 1, Regnery R. Human and tick spotted fever group rickettsia isolated from Israel: a genotypic analysis. J Clin Microbiol 1992;30:2653-6. 4. Wolach B, Franci S, Bogger-Goren S, Drucker M, Goldwasser RA, Sadan N, et al. Clinical and laboratory findings of spotted fever in Israeli children. Pediatr Infect Dis J 1989;8:152-5. 5. Yagupsky P, Wolach B. Fatal Israeli spotted fever in children. Clin Infect Dis 1993;17:850-3. 6. Agupsky P, Sarov B, Sarov I. A cluster of cases of spotted fever in a kibbutz in southern Israel. Scand J Infect Dis 1989;21:155-60. 7. Rotz L, Callejas L, McKechnie D, Wolfe D, Gaw E, Hathcock L, et al. An epidemiologic and entomologic investigation of a cluster of Rocky Mountain spotted fever cases in Delaware. Del Med J 1998;70:285-91. Iron and the Role of Chlamydia pneumoniae in Heart Disease To the Editor: Chronic infection of the coronary arteries by Chlamydia pneumoniae has been proposed as a heart disease risk factor (1). One reason for this proposal is the organism's association with one or more other risk factors for heart disease (2). However, an independent pathogenic role for C. pneumoniae in heart disease is unlikely if its presence is only a marker for another risk factor. In the Helsinki Heart Study (3), markers of chronic C. pneumoniae infection were a significant risk factor for a cardiac event, independent of most traditional risk factors; however, some association with known risk factors was seen, including a positive association with smoking and an unexpected negative association with spare-time physical activity. We postulate a key role for iron, a proposed risk factor for heart disease (4-6), in promoting the growth of C. pneumoniae in coronary arteries. Iron is an essential growth factor for nearly all pathogenic microorganisms (7). In particular, the growth of C. pneumoniae in a human lung cell line and in Hep-2 cells is strongly inhibited by iron restriction or by use of the iron chelator deferoxamine (8, P. Saikku, pers. comm.). Excess iron is present in atherosclerotic lesions. Seven times more iron is present in atherosclerotic than in healthy arteries (9). Among proposed risk factors for heart disease, iron provides the most conceptually straightforward explanation for the presence of C. pneumoniae in coronary vessels. We propose that chronic infection of coronary arteries by C. pneumoniae occurs only if excess iron is present in vivo. Excess iron is defined as stored iron or iron in excess of the amount needed to maximize hematocrit. This implies that C. pneumoniae can establish infection in the coronary arteries only if a threshold level of available iron is present. Confirmation of the hypothesis could explain an association of C. pneumoniae with coronary atherosclerosis and, more generally, with ischemic heart disease and would be consistent with the greater susceptibility of men than women to C. pneumoniae infection (2) and myocardial infarction. Moreover, confirmation of the hypothesis would leave open the question of whether C. pneumoniae is directly atherogenic or merely finds fertile ground for growth in arteries because of the presence of iron above some threshold level. Until age 20, men and women show few differences in prevalence of antibody titers against C. pneumoniae. After age 20, the prevalence of markers diverges sharply, with men showing a much steeper rise than women. This is similar to the patterns observed for both stored iron levels and rate of myocardial infarction in men and women, especially between the ages of 20 and 50 years (4,5). In later years, prevalence rates for C. pneumoniae markers do not rise as steeply for women as the curves for stored iron level or myocardial infarction rates (2). These patterns are compatible with associations between stored iron, myocardial infarction rate, and markers for infection with C. pneumoniae. Another relevant observation is the negative association of markers with spare-time physical activity (2). Such activity is associated with lower stored iron levels (10), which may decrease vulnerability to C. pneumoniae. The presence of excess iron in regulating susceptibility to C. pneumoniae does not readily explain the geographic gradient in the frequency of antibodies (2). C. pneumoniae infection seems to be more prevalent near the equator. In general, acquisition of stored iron is more problematic among impoverished persons, many of whom live near the equator. Parasitic infections that cause chronic iron loss from bleeding in the gut and bladder, along with limited availability of easily absorbed heme iron in meat, tend to minimize iron acquisition in these areas. C. pneumoniae may be endemic in populations near the equator, especially among children in tropical urban slums, because of other factors that eliminate any differential effects on the basis of iron levels. In these areas chlamydial antibodies may be a good marker for invasion but not necessarily for disease. We suggest that, above a modest threshold level of stored iron in vivo, C. pneumoniae acquires the ability to colonize coronary arteries. Invasion and colonization by the organism in vivo probably require a concentration of available iron similar to that needed for growth in cell culture. Even in a state of total iron depletion, iron is still present in the body in abundance. However, in iron depletion virtually all iron in the body is functional iron. Functional iron, i.e., iron in hemoglobin, may not be readily accessible to the organism. Our hypothesis implies that stored iron can be mobilized by C. pneumoniae for growth. An approach to testing the hypothesis would involve comparing the ability of C. pneumoniae to colonize macrophages from stored iron-replete persons with those from persons without stored iron. If the hypothesis is confirmed, maintenance of an iron-depleted state under medical supervision could be recommended as a preventive strategy against recolonization after a course of antibiotic therapy. Acknowledgment We thank Jane E. Raulston for review of the manuscript and for useful suggestions. Jerome L. Sullivan* and Eugene D. Weinberg† *University of Florida College of Medicine, Gainesville, Florida, USA; and †Indiana University, Bloomington, Indiana, USA References 1. Saikku P, Mattila K, Nieminen MS, Huttunen JL, Leinonen M, Ekman M-R, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;ii:983-5. 2. Saikku P. The epidemiology and significance of Chlamydia pneumoniae. J Infect 1992;25 Suppl I:27-34. 3. Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med 1992;15;116:273-8. 4. Sullivan JL. Iron and the sex difference in heart disease risk. Lancet 1981;1:1293-4. 5. Sullivan JL. Iron versus cholesterolperspectives on the iron and heart disease debate. J Clin Epidemiol 1996;49:1345-52. 6. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, Salonen R. High stored iron levels are associated with excess risk [ of myocardial infarction in eastern Finnish men. Circulation 1992;86:803-11. 7. Weinberg ED. Patho-ecologic implications of microbial acquisition of host iron. Reviews in Medical Microbiology 1998;9:171-8. 8. Freidank HM, Billing H. Influence of iron restriction on the growth of Chlamydia pneumoniae TWAR and Chlamydia trachomatis. Clinical Microbiology and Infection 1997;3 Suppl 2:193. 9. Thong PSP, Selley M, Watt F. Elemental changes in atherosclerotic lesions using nuclear microscopy. Cell Mol Biol 1996;42:103-10. 10. Lakka TA, Nyyssönen K, Salonen JT. Higher levels of conditioning leisure time physical activity are associated with reduced levels of stored iron in Finnish men. Am J Epidemiol 1994;140:148-60. Filth Flies Are Transport Hosts of Cryptosporidium parvum To the Editor: Infection with Cryptosporidium parvum, a zoonotic and anthroponotic coccidian parasite (1), may be fatal for persons with impaired immune systems (2), for whom a low number of oocysts can initiate life-threatening diarrhea (1). Insects such as promiscuous-landing synanthropic flies (i.e., coprophilic filth flies) are recognized transport hosts for a variety of parasites (3-5), but not for C. parvum. We assessed the role of synanthropic flies in the mechanical transmission of C. parvum oocysts. Bovine diarrheic feces (20-ml specimens) containing 2.0 x 105 oocysts/ml were placed in petri dishes in each of five 4-liter paper cages with approximately 250 pupae of laboratory-reared house flies (Musca domestica F58WTZ strain). Three days after the flies emerged, fecal specimens were collected on glass microscope slides placed in each cage. Thirty flies aspirated from each cage on days 3, 5, 7, 9, and 11 after emergence were eluted, and the eluants were processed by the cellulose acetate membrane (CAM)-filter dissolution method (6). Digestive tracts dissected from randomly selected flies and the glass slides with fly excreta were examined by immunofluorescent antibody (IFA) (7), and C. parvum oocysts were counted (8). Maggots of M. domestica were reared in fly larvae medium (PMI FEEDS, Inc., St. Louis, MO) contaminated with calf diarrheic feces (50 ml) containing 2.0 x 105 C. parvum oocysts/ml. Resulting pupae were eluted, the eluants were processed by the CAM-filter dissolution method (6), and C. parvum oocysts were identified by IFA (7) and counted (8). Diarrheic fecal specimens from a C. parvum-uninfected calf were used as negative controls in similar experiments. Randomly selected samples containing fly-derived C. parvum oocysts were processed with acid-fast stain (AFS) (8) to check for normal cellular morphologic features. Ten Victor-type flying-insect traps (Woodstream, Lititz, PA) were baited with rotten fish and placed inside a barn (approximately 880 m2) in which a male Holstein calf infected with C. parvum (AUCP-1 strain) was housed. The traps were emptied weekly, the flies were counted and identified (5,9), and the inside surfaces of the traps (containing fly excreta), along with the flies, were eluted with 200 ml of eluting fluid (6). The eluting fluid was filtered through a CAM (Millipore, Bedford, MA) (6,8), which was then processed (6), and C. parvum oocysts were identified by IFA (7) and counted (8). The mean number of C. parvum oocysts per droplet of M. domestica was 4 to 20 (mean 7.0 + 3.2), and the number of droplets increased over time. All flies harbored C. parvum oocysts on their external surfaces. On average, 14.0 + 6.8 fly excreta were counted per 1.0 cm2 of glass slide. From 1 to 8 C. parvum oocysts were detected in digestive tracts of flies exposed to feces with oocysts. C. parvum oocysts were also numerous on maggot and pupa surfaces; approximately 150 and 320 oocysts were recovered per maggot and pupa, respectively. Wild-caught flies belonged to the families Calliphoridae (96% of total flies), Sarcophagidae (2%), and Muscidae (2%). An average of eight flies was caught per trap, and more than 90% of flies harbored C. parvum oocysts. The number of trap-recovered C. parvum oocysts per fly was 2 to 246 (mean 73 oocysts per fly). Synanthropic flies that breed in or come in contact with a fecal substrate contaminated with C. parvum oocysts can harbor these oocysts both externally and internally and will mechanically deposit them on other surfaces. Therefore, synanthropic flies can serve as mechanical vectors for C. parvum oocysts and under poor sanitary conditions could be involved in the transmission of human and animal cryptosporidiosis. The biology and ecology of synanthropic flies indicate that their potential for mechanical transmission of C. parvum oocysts can be high. The morphologic and AFS and IFA staining characteristics of C. parvum oocysts recovered from the exoskeletons of flies and identified in their fecal spots suggest that oocysts are still viable. Thaddeus K. Graczyk,*† Ronald Fayer,‡ Michael R. Cranfield,*† Barbara Mhangami-Ruwende,* Ronald Knight,* James M. Trout,§ and Heather Bixler§ *Johns Hopkins University, Baltimore, Maryland, USA; †The Baltimore Zoo, Druid Hill Park, Baltimore, Maryland, USA; ‡U.S. Department of Agriculture, Beltsville, Maryland, USA; and §University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, USA References 1. Fayer R, Speer CA, Dubey JP. The general biology of Cryptosporidium. Cryptosporidium and cryptosporidiosis. In: Fayer R, editor. Boca Raton (FL): CRC Press; 1997. 1-42. 2. Graczyk TK, Fayer R, Cranfield MR. Zoonotic potential of cross-transmission of Cryptosporidium parvum: implications for waterborne cryptosporidiosis. Parasitol Today 1996;13:348-51. 3. Wallace GD. Experimental transmission of Toxoplasma gondii by filth-flies. Am J Trop Med Hyg 1971;20:411-3. 4. Hedges SA. Flies, gnats and midges. In: Malis A, editor. Handbook of pest control. Cleveland (OH): Franzak & Foster Co.; 1990. p. 621-84. 5. Greenberg B. Flies and diseases, biology and disease transmission. Princeton (NJ): Princeton University Press; 1973. p. 221. 6. Graczyk TK, Cranfield MR, Fayer R. Recovery of waterborne oocysts of Cryptosporidium parvum from water samples by the membrane-filter dissolution method. Parasitol Res 1997;83:121-5. 7. Graczyk TK, Cranfield MR, Fayer R. Evaluation of commercial enzyme immunoassay (EIA) and immunofluorescent antibody (IFA) test kits for detection of Cryptosporidium oocysts of species other than Cryptosporidium parvum. Am J Trop Med Hyg 1996;54:274-9. 8. Graczyk TK, Fayer R, Cranfield MR, Owens R. Cryptosporidium parvum oocysts recovered from water by the membrane filter dissolution method retain their infectivity. J Parasitol 1997;83:111-4. 9. Borror DJ, DeLong DM, Triplehorn CA. An introduction to the study of insects. Philadelphia (PA): Saunders College Publishing; 1981. p. 827. The Cost-Effectiveness of Vaccinating against Lyme Disease To the Editor: The recent article by Meltzer and colleagues (1) is an important contribution to a pertinent public health issue: who should receive the newly licensed Lyme disease vaccine. Answering this question is a daunting task, given the scarcity of valid data. Estimates of the spectrum and prevalence of the long-term sequelae of Lyme disease remain controversial (2-4). In generating their cost-effectiveness model, Meltzer et al. examined the cost savings involved in preventing three categories of classic organ-specific Lyme disease sequelae (cardiovascular, neurologic, and arthritic); however, they did not take into account the potential cost savings from preventing cases of a generalized symptom complex known as post-Lyme syndrome, which includes persisting myalgia, arthralgia, headache, fatigue, and neurocognitive deficits. These generalized sequelae, which are recognized by the National Institutes of Health as late sequelae of Lyme disease, have been found to persist for years after antibiotic therapy (5,6). Two population-based retrospective cohort studies (7,8) among Lyme disease patients whose illness was diagnosed in the mid-1980s determined that one third to half had clinically corroborated post-Lyme syndrome symptoms years after the initial onset of disease. Although these studies were conducted 15 years ago, when optimal antibiotic regimen guidelines were still evolving, the estimated cost of averting these often-disabling nonorgan-specific symptoms should also be taken into account in estimated sensitivity analyses of vaccine cost-effectiveness. The cost of treating sequelae is weighted heavily in the cost-effectiveness models presented by Meltzer and colleagues, which adds importance to considering post-Lyme syndrome. Nevertheless, we recognize the difficulty of this modeling, especially in the absence of validated cost-of-treatment data for these generalized symptoms. A point of correction is that Meltzer et al. erroneously cite one of these studies (7) to infer that the long-term clinical sequelae of Lyme disease lasted a mean of 6.2 years from the onset of disease. In this retrospective study, Shadick et al. evaluated 38 persons with a clinical history of Lyme disease a mean of 6.2 years from the onset of disease regardless of the presence of persisting symptoms; 25 of these patients had no residual symptoms at follow-up. To accurately estimate the duration of clinical sequelae, longitudinal evaluations of representative populations of Lyme disease patients will be required because late manifestations have been demonstrated months to years after diagnosis (9,10). Dimitri Prybylski University of Maryland School of Medicine, Baltimore, Maryland, USA References 1. Meltzer MI, Dennis DT, Orloski KA. The cost-effectiveness of vaccinating against Lyme disease. Emerg Infect Dis 1999;5:321-8. 2. Ellenbogen C. Lyme disease. Shift in the paradigm? Arch Fam Med 1997;6:191-5. 3. Liegner KB. Lyme disease: the sensible pursuit of answers. J Clin Microbiol 1993;31:1961-3. 4. Sigal LH. Persisting symptoms of Lyme diseasepossible explanations and implications for treatment [editorial]. J Rheumatol 1994;21:593-5. 5. National Institute of Allergy and Infectious Diseases. Research on chronic Lyme disease. National Institutes of Health Office of Communications Fact Sheet; May 1997. 6. National Institute of Allergy and Infectious Diseases. Emerging infectious diseasesNIAID research. National Institutes of Health Fact Sheet; Mar 1998. 7. Shadick NA, Phillips CB, Logigian EL, Steere AC, Kaplan RF, Berardi VP, et al. The long-term clinical outcomes of the disease. A population-based retrospective cohort study. Ann Intern Med 1994;121:560-7. 8. Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and post-infectious syndrome. J Rheumatol 1994;21:454-61. 9. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990;323:1438-44. 10. Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med 1991;325:159-63. Emerging Infectious Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA URL: ftp://ftp.cdc.gov/pub/EID/vol5no5/ascii/letters.txt 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.