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Letters


Infectious Diseases and Mental Illness: Is There a Link?

To the Editor: The report by Hatalski et al. (1) on Borna virus as a probable human pathogen provides yet another example of an infectious agent being tentatively associated with neuropsychiatric disorders. Earlier this year, researchers at Rockefeller University and the National Institute of Mental Health suggested that after streptococcal infection, some children may be at increased risk for obsessive-compulsive disorders and Tourette syndrome (2). The human B-cell antigen D8/17, believed to be a marker for increased susceptibility to poststreptococcal rheumatic heart disease, has been tentatively linked to this increased risk for psychiatric illness in children. Other reports of patients with complicated Lyme borreliosis, including some whose infections have progressed to encephalopathies, describe persistent verbal and memory deficits among these patients (3). In a few Lyme disease patients, the only overt symptoms of disease at the time of initial diagnosis and treatment were classified as mental confusion (4). Two newly emergent infectious diseases in the United States, leptospirosis and neurocysticercosis, have been found among inner city residents and poor immigrants, respectively. Occasionally leptospirosis has been associated with a variety of postinfectious psychiatric symptoms, including depression, dementia, and psychosis (5). Neurocysticercosis, a tropical parasitic infection, is increasingly associated with emergency room admissions for seizures and epilepsy (6). Still other infectious diseases are being examined for links with cognitive symptoms and emotional disorders.

The primary cause of many common psychiatric disorders, including depression, manic depression, anxiety, and schizophrenia, remains a mystery. The World Health Organization estimates that 1.5 billion people worldwide suffer from a neuropsychiatric disorder. Of the 10 leading causes of disability in 1990, four were psychiatric disorders: unipolar depression, manic depression, schizophrenia, and obsessive-compulsive disorders (7). The National Institute of Mental Health recently estimated that as many as 20% of young Americans ages 7 to 14 approximately 10 million children have mental health problems severe enough to compromise their ability to function (8). Infectious agents may play a role in some of these diseases to some unknown degree. A better understanding of the role of infection may speed treatment and prevention efforts and reduce the degree of disability and stigma associated with mental illness.

Vaccines and antimicrobial agents might enhance current therapeutic options for mental illnesses. Even if infectious diseases were a primary factor in only 1% of neuropsychiatric illnesses, some 10 million persons might benefit from antimicrobial therapies. Identifying those susceptible to neuropsychiatric illnesses (because of environmental factors or genetic predisposition) may also permit vaccination or antimicrobial prophylaxis and a subsequent lowering of disease incidence.

Physicians and federal agencies addressing the problems of emerging infectious diseases should examine the possibility of infection as a cause of mental illness. Better communication among infectious disease and mental health experts, as well as additional training, will be needed to shed light on the growing phenomenon of infectious diseases manifesting themselves as neuropsychiatric disorders.

Edward McSweegan
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA

References

  1. Hatalski CG, Lewis AJ, Lipkin WI. Borna disease. Emerg Infect Dis 1997;3:129-35.
  2. Swedo SE, Leonard HL, Mittleman BB, Allen AJ, Rapoport JL, Dow SP, et al. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry 1997;154:110-2.
  3. Benke T, Gasse T, Hittmair-Delazer M, Schmutzhard E. Lyme encephalopathy: long-term neuropsychological deficits years after acute neuroborreliosis. Acta Neurol Scand 1995;91:353-7.
  4. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry 1994;151:1571-83.
  5. Mumford C, Dudley N, Terry H. Leptospirosis presenting as a flaccid paraplegia. Postgrad Med J 1990;66:218-20.
  6. Garcia H, Tsang V, Gonzalez A, Gilman R. Cysticercosis in the U.S. and Peru. Presented at the 6th Annual National Institutes of Health International Centers for Tropical Disease Research Meeting; 1997 May 5-7; Bethesda, Maryland.
  7. World Health Organization. The global burden of disease [cited 1998 Jan 5]; [2 screens]. Available from URL: http://www.who.ch/programmes/mnh/msamain.htm
  8. Children's mental health research severely neglected, says National Institute of Mental Health Director. Washington Fax [serial online] 1997 Apr 8 [cited 1998 Jan 5]. Available from URL: http://www.washington-fax.com

Mycobacterium nonchromogenicum Bacteremia in an AIDS Patient

To the Editor: Mycobacterium avium complex is the most common nontuberculous mycobacterium that causes disseminated infection in HIV-positive patients (1). Other less common nontuberculous mycobacteria responsible for disseminated disease in these patients are M. fortuitum (2), M. genavense (3), M. gordonae (4), M. haemophilum (5), M. kansasii (6), M. malmoense (7), M. marinum (8), M. scrofulaceum (9), M. simiae (10), M. szulgai (11), M. terrae (9), and M. xenopi (2,9). Although only M. genavense, M. kansasii, and M. xenopi are significantly more frequent in these patients (2,3,9), HIV infection is likely a predisposing condition for all nontuberculous mycobacterial infections. We report the first case of disseminated infection caused by M. nonchromogenicum in an HIV-infected patient.

A 28-year-old man with HIV infection acquired by sharing injection tools was seen in our outpatient clinic because of intermittent fever, drenching nocturnal sweats, and cough with purulent sputum of 4 months' duration. He also reported a weight loss of 10 kg in the previous 2 months. He had been treated for bronchial infection with an unknown antibiotic in another hospital. After this treatment, respiratory symptoms had improved somewhat, but fever and constitutional symptoms continued. His only previous opportunistic infection had been recurrent oral and esophageal candidiasis. The last CD4-cell count had been 16/µL 1 year earlier, and he was receiving didanosine and prophylactic therapy with cotrimoxazole and fluconazole. On physical examination the patient appeared ill; he was febrile, cachectic, and had thrush and oral hairy leukoplakia. Neither lymphadenopathy nor abnormal cardiopulmonary symptoms were found. The liver, which had enlarged since the last examination, was palpated 6 cm below the right costal margin. Abnormal laboratory values included aspartate aminotransferase 61 U/L, gamma-glutamyl transferase 209 U/L, lactate dehydrogenase 516 U/L, hemoglobin 12.3 g/dL, leukocyte count 4,300/µL (66% neutrophils, 19% band forms, 1% metamyelocytes, 3% lymphocytes, 11% monocytes), platelet count 130,000/L, and erythrocyte sedimentation rate 72 mm/h. Chest X-rays were unremarkable, and a set of blood cultures was sterile. A sputum culture yielded Haemophilus influenzae sensitive to ampicillin, and smears and cultures for mycobacteria in one stool and three sputum samples were negative.

The patient was treated with oral amoxicillin for 2 weeks without improvement. Empirical therapy against M. avium complex with clarithromycin, ciprofloxacin, and ethambutol was started; the patient's condition improved dramatically within the next few days, and the fever and diaphoresis disappeared, although cough and sputum production remained unchanged. Three weeks later, a slow-growing nonphotochromogenic mycobacterium, identified as M. nonchromogenicum in a reference laboratory (Centro Nacional de Microbiología, Majadahonda, Madrid, Spain) by biochemical tests and confirmed by polymerase chain reaction-restriction enzyme pattern analysis, was isolated from a blood sample obtained on admission. This microorganism was sensitive to the three drugs administered, and the treatment was continued. Two months later the patient had gained 10 kg, hemoglobin had increased to 13.8 g/dL, the erythrocyte sedimentation rate had decreased to 52 mm/h, and the differential leukocyte count had returned to normal. Antimycobacterial drugs were withheld after 1 year of treatment. Twenty-two months after the diagnosis, the patient is doing well. He is receiving combination antiretroviral therapy, and his CD4-cell count is 128/µL.

M. nonchromogenicum, a slow-growing nonpigmented (Runyon's group III) mycobacterium, belongs to the M. terrae complex, together with M. triviale; it is traditionally considered nonpathogenic. However, it has been involved in a few cases of pulmonary infection (12) and chronic tenosynovitis secondary to puncture wounds (13), like the related organism M. terrae. In fact, some authors think that M. nonchromogenicum is the true pathogen in the M. terrae complex (13), and it is possible that some reports have misidentified this organism. This complex was first isolated in soil washings from radishes, but it has been found to be ubiquitous in the aquatic environment, including a hospital potable water supply (14).

Unlike osteoarticular infections, which commonly occur in previously healthy people, the scanty reports on pulmonary and disseminated infection by M. terrae complex suggest that either immunosuppression or local predisposing conditions (e.g., tuberculous cavities) are necessary pathogenetic cofactors (15). To our knowledge, M. nonchromogenicum bacteremia has never been reported before.

No specific DNA probes exist for M. terrae complex, but false-positive reactions with M. tuberculosis complex DNA probes have been described (16). Isolates are usually resistant to most antituberculosis drugs, with the exception of ethambutol and streptomycin, and susceptible to erythromycin, ciprofloxacin, and sulfonamides.

Only one case of disseminated infection by M. terrae has been described in a patient with advanced HIV infection and positive cultures in blood and bronchoalveolar lavage fluid, but no additional data were provided (9). Although the isolate we recovered might represent a laboratory contaminant, several pieces of evidence make this possibility very unlikely: lack of alternative explanation for a persistent and progressive clinical picture of 4 months' duration, absence of response to standard antibiotic therapy, negative results in the search for other pathogens, rapid and sustained clinical and laboratory response to drugs active against this strain, clear improvement despite the lack of treatment for other conditions, and absence of other isolates of this pathogen in our hospital despite the large number of samples examined for mycobacteria.

Acknowledgments

We are indebted to María Soledad Jiménez, Mycobacterial Laboratory of the Centro Nacional de Microbiología, Majadahonda, Madrid, for providing the microbiologic data.

José Mayo, Julio Collazos, and Eduardo Martínez
Hospital de Galdakao, Vizcaya, Spain

References

  1. Nightingale SD, Byrd LT, Southern PM, Jockusch JD, Cal SX, Wynne BA. Incidence of Mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. J Infect Dis 1992;165:1082-5.
  2. Raszka WV Jr, Skillman LP, McEvoy PL, Robb ML. Isolation of nontuberculous, non-avium mycobacteria from patients infected with human immunodeficiency virus. Clin Infect Dis 1995;20:73-6.
  3. Bessesen MT, Shlay J, Stone-Venohr B, Cohn DL, Reves RR. Disseminated Mycobacterium genavense infection: clinical and microbiological features and response to therapy. AIDS 1993;7:1357-61.
  4. Lessnau KD, Milanese S, Talavera W. Mycobacterium gordonae: a treatable disease in HIV-positive patients. Chest 1993;104:1779-85.
  5. Straus WL, Ostroff SM, Jernigan DB, Kiehn TE, Sordillo EM, Armstrong D, et al. Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients. Ann Intern Med 1994;120:118-25.
  6. Parenti DM, Symington JS, Keiser J, Simon GL. Mycobacterium kansasii bacteremia in patients infected with human immunodeficiency virus. Clin Infect Dis 1995;21:1001-3.
  7. Chocarro A, González-López A, Breznes MF, Canut A, Rodríguez J, Diego JM. Disseminated infection due to Mycobacterium malmoense in a patient infected with human immunodeficiency virus. Clin Infect Dis 1994;19:203-4.
  8. Tchornobay AM, Claudy AL, Perrot JL, Levigne V, Denis M. Fatal disseminated Mycobacterium marinum infection. Int J Dermatol 1992;31:286-7.
  9. Schafer RW, Sierra MF. Mycobacterium xenopi, Mycobacterium fortuitum, Mycobacterium kansasii, and other nontuberculous mycobacteria in an area of endemicity for AIDS. Clin Infect Dis 1992;15:161-2.
  10. Valero G, Peters J, Jorgensen JH, Graybill JR. Clinical isolates of Mycobacterium simiae in San Antonio, Texas: an 11-yr review. Am J Respir Crit Care Med 1995;152:1555-7.
  11. Roig P, Nieto A, Navarro V, Bernacer B, Borras R. Micobacteriosis por Mycobacterium szulgai en paciente con infección por el virus de la inmunodeficiencia humana. An Med Interna 1993;10:182-4.
  12. Tsukamura M, Kita N, Otsuka W, Shimoide H. A study of the taxonomy of the Mycobacterium nonchromogenicum complex and report of six cases of lung infection due to Mycobacterium nonchromogenicum. Microbiol Immunol 1983;27:219-36.
  13. Ridderhof JC, Wallace RJ Jr, Kilburn JO, Butler WR, Warren NG, Tsukamura M, et al. Chronic tenosynovitis of the hand due to Mycobacterium nonchromogenicum: use of high-performance liquid chromatography for identification of isolates. Rev Infect Dis 1991;13:857-64.
  14. Lockwood WW, Friedman C, Bus N, Pierson C, Gaynes R. An outbreak of Mycobacterium terrae in clinical specimens associated with a hospital potable water supply. American Review of Respiratory Diseases 1989;140:1614-7.
  15. Peters EJ, Morice R. Miliary pulmonary infection caused by Mycobacterium terrae in an autologous bone marrow transplant patient. Chest 1991;100:1449-50.
  16. Ford EG, Snead SJ, Todd J, Warren NG. Strains of Mycobacterium terrae complex which react with DNA probes for M. tuberculosis complex. J Clin Microbiol 1993;31:2805-6.

Escherichia coli O157:H7 Infection in Colombia

To the Editor: The prevalence of Escherichia coli O157:H7 in Colombia is not known; we conducted a study to determine its prevalence in children with infectious diarrhea, in adult cattle, and in ground beef.

Between March 1996 and March 1997, we examined 538 children under 5 years of age with infectious diarrhea who had been admitted to either of the two children's hospitals in Bogotá. Diarrhea was defined as three or more loose stools within the previous 24 hours. One hundred and sixty-one children under 10 years of age admitted to the hospital for a medical reason other than infectious diarrhea served as controls.

Stool samples from children with and without diarrhea were placed in Stuart transport medium and sent to the laboratory within 24 hours; the samples were injected into sorbitol MacConkey agar (Oxoid Basingstoke, United Kingdom). After 24 hours of incubation at 37°C, sorbitol nonfermenting colonies were tested with 4-methylumbelliferyl-ß-glucuronide (MUG); all typical colonies of E. coli O157:H7 that were sorbitol-negative were confirmed as E. coli by biochemical tests (1,2) and were tested for agglutination with a latex test kit (Oxoid Basingstoke, United Kingdom) for detecting E. coli O157 and E. coli H antiserum H7 (Difco, Detroit, MI, USA). All human isolates were confirmed as Shiga-toxin producers by latex agglutination (Oxoid Basingstoke, United Kingdom). We used as a control strain E. coli O157:H7 provided by M. Karmali.

Rectal swabs from 307 healthy adult cattle from farms in Cundinamarca and Meta Departments were placed in Stuart transport medium, stored at 4°C, and transported to the laboratory within 6 hours. Swabs were injected into sorbitol MacConkey agar, and colonies that did not ferment sorbitol were characterized by standard techniques (3).

One hundred and fifty beef patties (31 cooked, 119 raw), collected in Bogotá, were examined by direct plating and enrichment culturing. Samples (1.0 g each) were serially diluted (1:10) in 0.85% NaCl solution, and 0.1 ml portions were plated in duplicate onto sorbitol MacConkey agar. Serologic and biochemical confirmation was done as mentioned above.

E. coli O157:H7 prevalence among children was 7.2%, with an age range of 0–60 months (average 21 months); diarrheal illness lasted an

average of 2.5 days. Of 39 patients, eight were 6 months old or younger, five were 6 to 12 months old, 17 were 12 to 24 months old, and nine were older than 24 months. Renal failure associated with hemolytic uremic syndrome (HUS) developed in three (7.7%). Epidemiologic data were not collected regarding contaminated foods as a possible source of E. coli O157:H7 infection in the patients. E. coli O157:H7 was isolated from five (3.1%) of the 161 controls; the prevalence of E. coli O157:H7 was substantially higher in patients with infantile diarrhea than in controls.

All 39 strains from human cases were sorbitol-negative; five did not display MUG activity. Overall, 39 strains agglutinated strongly with antiserum O157:H7. Antimicrobial susceptibility tests were performed by the Bauer method (4). All E. coli O157:H7 isolated were susceptible to ciprofloxacin; 92% were resistant to ampicillin; 76% were resistant to furazolidone; and 76% were resistant to trimethoprim-sulfamethoxazole (TMP-SMZ).

E. coli O157:H7 was isolated from 20 (6.5%) of 307 rectal swabs from cattle. The strains isolated were sorbitol-negative and agglutinated strongly with antisera; five did not present activity. All strains were susceptible to ciprofloxacin; 90% were resistant to ampicillin; and 26% were resistant to TMP-SMZ. E. coli O157:H7 was isolated from 13 (87%) of 150 beef patties, six from raw beef, and seven from cooked beef.

Stool cultures of all patients with acute bloody diarrhea should be tested for E. coli O157:H7 to identify those at risk for HUS (5); however, serotyping, cytotoxicity assays, or DNA probing for E. coli O157:H7 are not routinely performed in Colombia.

This preliminary report suggests that E. coli O157:H7 is emerging as an important cause of endemic childhood diarrhea in Colombia and that the chain of contamination is present. The incidence is greatly underestimated because of limited surveillance and reporting. Further studies are needed to identify the pathogenic mechanisms of these E. coli O157:H7 strains and to determine the fecal carriage rate in healthy children. Data obtained will help elucidate the role of E. coli O157:H7 in childhood diarrhea. In addition, molecular analysis should be performed to establish the connection between the strains isolated from different sources in Colombia.

Our findings suggest that the risk for E. coli O157:H7 infection in Colombia is high; therefore,

more active screening and surveillance would enhance case detection, epidemiologic understanding of E. coli O157:H7 infection and HUS, and could lead to more specific therapeutic interventions.

Salim Mattar and Elizabeth Vásquez
Facultad de Ciencias, Universidad Javeriana, Bogotá, Colombia

References

  1. Bockemuhl J, Aleksic S, Karch H. Serological and biochemical properties of Shiga-like toxin (verocytotoxin)-producing strains of Escherichia coli, other than O-group 157, from patients in Germany. Zentralbl Bakteriol 1992;276:189-95.
  2. Gunzer F, Bohm H, Rossmann H, Bitzan M, Aleksic S, Karch H. Molecular detection of sorbitol-fermenting Escherichia coli O157 in patients with hemolytic-uremic syndrome. J Clin Microbiol 1992;30:1807-10.
  3. Chapman PA, Siddons CA, Wright DJ, Norman P, Fox J, Crick E. Cattle as a possible source of verocytotoxin-producing Escherichia coli O157 infections in man. Epidemiol Infect 1993;439:447.
  4. Bauer AW, Kirby WMM, Sherris JC, Turk M. Antibiotic susceptibility testing by a standardized single disc method. Am J Clin Pathol 1966;45:493-6.
  5. Wells JG, Davis BR, Wachsmuth IK, Riley LW, Remis RS, Sokolow R, Morris GK. Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia serotype. J Clin Microbiol 1983;18:512-20.

Autofluorescence and the Detection of Cyclospora Oocysts

To the Editor: From May through July 1997, we searched for the seasonally occurring Cyclospora cayetanensis, along with other coccidia and microsporidia, in fecal samples from 385 patients. The samples, in 10% formalin for evaluation of coccidia and microsporidia, were initially processed by a routine formalin-ethyl acetate concentration method; the parasite was detected in 18 patients (1,2). The resulting sediment was examined as follows. A drop of sediment was placed on a slide, cover-slipped, and examined microscopically as a wet mount at 200x and 400x magnification and subsequently at 200x magnification by epifluorescence with a 330 to 380 nm UV filter. Four smears were also prepared and stained by routine trichrome (2), modified trichrome (3), auramine-rhodamine (4), and Kinyoun acid-fast (5) procedures. All wet mount and stained preparations were evaluated by at least two trained persons.

Of the 385 fecal samples examined, 18 were positive for C. cayetanensis. The positive samples were from eight states, which encompassed northeastern (Rhode Island, New York, Massachusetts, Pennsylvania), midwestern (Wisconsin), western (Oregon, California), and southern (Florida) sections of the United States.

In 12 of 18 patients, the organisms were detected without much difficulty in wet mounts as round or partially collapsed nonrefractile bodies; however, in the other six, repeated wet preparations were needed to detect the organisms. When the same wet mounts were examined with epifluorescence microscopy, oocysts were easily discerned in all samples, even the six in which repeated wet preparations and stains were needed. While the trichrome procedures were ineffective, the auramine-rhodamine and Kinyoun stains gave varied results. The autofluorescence technique, however, was distinctly superior to the wet mount and staining procedures.

Extensive outbreaks of diarrhea caused by C. cayetanensis were reported in 1997 from different parts of the United States (6-8), and several procedures have been used to confirm the diagnosis in clinical samples. While the organisms are large enough to be seen in direct wet mounts, they are frequently caught up in mucus or covered by debris, so they are difficult to detect. Autofluorescence in C. cayetanensis oocysts makes them easily visible in clinical samples (1,9) with the use of a 330 to 380 nm UV filter; this feature enhanced their detection at least twofold over the direct wet mount, especially when the wet mount and stained slides contained few oocysts. (The same wet mount preparation can be used for the epifluorescence procedure.)

The 18 patients with cyclosporiasis were ages 2 to 71 years, which indicates that the infection was not specific to any age group. Twelve of the 18 cases were in women. Massachusetts had 11, the largest number of C. cayetanenis-positive patients. Of the 18, 16 were adults; the other two were children with a coexisting parasite (Dientamoeba fragilis). In one instance, three members of the same family were infected, the parents with only C. cayetanensis, the son with D. fragilis and Blastocystis hominis.

Because C. cayetanensis is a seasonal diarrheal agent, fecal samples from persons with persistent unexplained explosive diarrhea during the summer should be carefully evaluated for this infection. Stool specimens should be fixed in 10% formalin and examined with autofluorescence microscopy for enhanced detection.

O.G.W. Berlin,*† J.B. Peter,† C. Gagne,† C.N. Conteas,‡ and L.R. Ash*
*School of Public Health, University of California, Los Angeles, California, USA; †Specialty Laboratories, Santa Monica, California, USA; and ‡Kaiser Permanente Medical Center, Los Angeles, California, USA

References

  1. Berlin OGW, Novak SM, Porschen RK, Long EG, Stelma GN, Schaeffer FW. Recovery of Cyclospora organisms from patients with prolonged diarrhea. Clin Infect Dis 1994;18:606-9.
  2. Ash LR, Orihel TC. Collection and preservation of feces. Parasites: a guide to laboratory procedures and identification. Chicago: ASCP Press; 1991. p. 3-53.
  3. Weber R, Bryan RT, Owen RL, Wilcox CM, Gorelkin L, Visvesvara GS. Improved light microscopical detection of microsporidia spores in stool and duodenal samples. N Engl J Med 1992;326:161-6.
  4. Berlin OGW. Mycobacteria. In: Baron EJ, Finegold SM, editors. Diagnostic microbiology. 8th ed. St. Louis: C.V. Mosby; 1990. p. 597-640.
  5. Ash LR, Orihel TC. Atlas of human parasitology. 4th ed. Chicago: ASCP Press; 1997.
  6. Centers for Disease Control and Prevention. Update: outbreaks of cyclosporiasisUnited States, 1997. MMWR Morb Mortal Wkly Rep 1997;46:451-2.
  7. Centers for Disease Control and Prevention. Update: outbreaks of cyclosporiasisUnited States and Canada, 1997. MMWR Morb Mortal Wkly Rep 1997;46:521-3.
  8. Colley DG. Widespread food-borne cyclosporiasis outbreaks present major challenges. Emerg Infect Dis 1996;2:354-6.
  9. Eberhard ML, Pienazek NJ, Arrowood MJ. Laboratory diagnosis of Cyclospora infections. Arch Pathol Lab Med 1997;121:792-7.

Partnerships for Detecting Emerging Infectious Diseases: Nepal and Global Influenza Surveillance

To the Editor:With new influenza strains emerging each year, identification of circulating strains by coordinated global surveillance is crucial to vaccine development for the coming year (1-3). Approximately 110 laboratories in 80 countries voluntarily participate in the World Health Organization (WHO) influenza surveillance network (4). Comprehensive surveillance is especially important in Asia, since new influenza strains often originate there. To participate in influenza global surveillance, countries need not rely on their own laboratory capability. Clinical specimens from patients thought to have influenza can be sent to designated laboratories around the world for analysis. A unique partnership has led to the expansion of the WHO global influenza surveillance network to Nepal.

The U.S. Army Medical Component—Armed Forces Research Institute for Medical Sciences (AFRIMS) (5) in Bangkok, Thailand, is well situated to assist with surveillance in Asia. Scientists at AFRIMS have conducted medical research in collaboration with Nepali colleagues for more than 20 years. Several studies have been conducted in collaboration with the CIWEC Clinic Travel Medicine Center (a travel medicine clinic that serves the diplomatic, aid, and tourist communities in Nepal). The clinic has approximately 5,000 patient visits per year, of which half are drawn from the 2,500 expatriates in Nepal and half from the 200,000 non-Indian tourists who visit Nepal annually.

A protocol was developed for a pilot influenza surveillance program. The staff of the CIWEC Clinic was responsible for volunteer recruitment, clinical evaluation, and specimen collection. Febrile upper respiratory infections were defined as temperature > 100°F (37.8°C, oral or equivalent) and cough or sore throat of 72 hours duration. Other symptoms, such as streptococcal pharyngitis, were excluded. No age or gender restrictions were included. Volunteers had to have been in Nepal for the 5 days preceding illness. Only the first patient in any single household with similar symptoms within days of other household members was asked to participate.

The AFRIMS field station in Kathmandu (locally known as the Walter Reed/AFRIMS Research Unit—Nepal or WARUN) was responsible for shipping specimens collected by the CIWEC Clinic to AFRIMS, Thailand. Since dry ice was not available in Kathmandu, dry ice and shipping containers were sent by AFRIMS, Thailand for use by WARUN. Shipments from WARUN were then sent back to AFRIMS, where specimens were repacked in dry ice and sent for testing at the central laboratory of the U.S. Air Force's Project Gargle (6) in San Antonio, Texas. Project Gargle has been testing viral respiratory specimens from distant Air Force installations for more than 20 years. Each specimen was tested for influenza A and B; parainfluenza virus 1, 2, and 3; adenovirus, enterovirus; and herpesvirus. Characterization of selected influenza A and B isolates by hemagglutination-inhibition testing was performed by the Centers for Disease Control and Prevention (CDC).

Between December 1996 and February 1997, the CIWEC staff collected specimens from 18 patients. Samples were collected from 11 (61%) residents and seven (39%) tourists, who were evenly distributed by gender and had a median age of 35 years. Influenza B/Beijing/184/93-like viruses were isolated from five (28%) of the 18 specimens. All patients from whom influenza viruses were obtained had mild illnesses with fever and upper respiratory syndromes. Herpes virus type 1 and adenovirus type 6 were each identified in one other specimen. No respiratory viruses were identified in the remaining 11 specimens.

Because of the importance of China in the emergence of new strains of influenza, CDC's WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza has worked with colleagues in China to establish a national Chinese network of influenza surveillance sites. Analysis of viruses isolated in China between 1988 and 1997 in comparison with other viruses obtained through WHO's global influenza surveillance network has shown that influenza variants are frequently identified in China before becoming prevalent in other regions of the world. Nepal is another especially valuable surveillance site, given its location between China and India (at the crossroads between northern and southern Asia) and its historic importance as a trans-Himalayan trade route.

Especially relevant are data from China demonstrating that the two antigenically and genetically distinct lineages of influenza B viruses represented by B/Victoria/02/87 and B/Yamagata/16/88 (7) have continued to circulate and evolve in China, while only viruses related to B/Yamagata have been detected elsewhere in the world and are represented in the current trivalent vaccine by the B/Bejing/184/93-like component. Virologic surveillance in surrounding countries (8) such as Nepal is necessary to detect geographic spread of B/Victoria-like virus in the region. Our data suggest that these viruses have not yet spread to Kathmandu.

Our unique international partnership between several civilian and military organizations (e.g., CIWEC Clinic, CDC, U.S. Air Force, and U.S. Army) demonstrates the feasibility of such partnerships as well as the usefulness of influenza surveillance data at both the local and global levels. Despite the small number of isolates obtained during this study, we were able to determine that the influenza B component of the trivalent vaccine prepared for the 1996-1997 influenza season would likely have offered protection for travelers and the local population against the influenza B strains isolated in Kathmandu. Ongoing surveillance data will establish geographic and temporal patterns of circulation of influenza viruses and thus provide valuable information for guiding public health policies for influenza vaccination. On a global level, these data are useful for annual vaccine strain selection.

Advances in communication, laboratory, and specimen transport technologies contributed greatly to the identification of viral pathogens from a new sentinel surveillance site in Nepal. In evaluating future collaborative sites, prior surveillance experience and reliable specimen shipping should be prime considerations. Approaches that use existing resources might foster greater international cooperation toward improved global detection and reporting of infectious diseases.

Acknowledgment

Financial support was given by the United States Department of Defense Emerging Infectious Disease Program.

Jeffrey M. Gambel,* David R. Shlim,† Linda C. Canas,‡ Nancy J. Cox,¶ Helen L. Regnery,§ Robert M. Scott,§ David W. Vaughn,§ Charles H. Hoke Jr.,* and Patrick W. Kelley*
*Walter Reed Army Institute of Research, Washington, D.C., USA; CIWEC Clinic, Kathmandu, Nepal; ‡Armstrong Laboratory - Diagnostic Virology, Brooks Air Force Base, Texas, USA; ¶Centers for Disease Control & Prevention, Atlanta, Georgia, USA; and §Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

References

  1. Gross PA. Preparing for the next influenza pandemic: a reemerging infection. Ann Internal Med 1996;124:682-5.
  2. Glezen WP. Emerging infections: pandemic influenza. Epidemiol Rev 1996;18:64-76.
  3. Patriarca PA, Cox NJ. Influenza pandemic preparedness plan for the United States. J Infect Dis 1997;176(Suppl 1):S4-S7.
  4. Hampson AW. Surveillance for pandemic influenza. J Infect Dis 1997;176(Suppl 1):S8-S13.
  5. Gambel JM, Hibbs RG. U.S. military overseas medical research laboratories. Mil Med 1996;161:638-45.
  6. Williams RJ, Cox NJ, Regnery HL, Noah DL, Khan AS, Miller JM, ET AL. Meeting the challenge of emerging pathogens: the role of the United States Air Force in global influenza surveillance. Mil Med 1997;162:82-6.
  7. Rota PA, Hemphill ML, Whistler T, Regnery HL, Kendal AP. Antigenic and genetic characterization of the hemagglutinins of recent circulating strains on influenza type B virus. J Gen Virol 1992:73:2737-42.
  8. Centers for Disease Control and Prevention. Update influenza activity—United States and worldwide, 1996-97 season, and composition of the 1997-98 influenza vaccine. MMWR Morb Mortal Wkly Rep 1997;46:325-30.

HIV-2 Infection and HIV-1/HIV-2 Dual Reactivity in Patients With and Without AIDS-Related Symptoms in Gabon

To the Editor: Between 1996 and 1997, we evaluated the incidence of HIV-2 infection at the Fondation Jeanne Ebori, the second largest hospital in Libreville, capital of Gabon; we found an unexpected high prevalence of HIV-2–infected or HIV-1/HIV-2–dually reactive patients.

During a 10-month period, 147 (14.3%) of 1,029 sera from inpatients and outpatients were found HIV-positive by the type III method recommended by the World Health Organization (two enzyme-linked immunosorbent assays are used to screen anti-HIV antibodies) (1). Further discrimination between HIV-1 and HIV-2 infections was assessed by using synthetic peptides specific for the gp41 and the gp120 of HIV-1 and the gp36 of HIV-2 (ImmunoComb II, PBS Orgenics, Illkirch, France). Of the 147 HIV-positive sera, 141 (96.0%) were exclusively HIV-1–positive; four were exclusively HIV-2–positive; and two were both HIV-1– and HIV-2–positive. Of the six sera with anti-gp36/HIV-2 reactivities, two (from patients A and B) were positive on HIV-2 Western blot, with marked anti-gag HIV-1 cross-reactivity and a discrimination assay positive only for HIV-2; two (from patients D and E) were positive on HIV-2 Western blot, with anti-gag and pol reactivities markedly lower than anti-env reactivities and a discrimination assay positive only for HIV-2; the two remaining sera (from patients C and F) showed typical dual reactivities for HIV-1 and HIV-2 infections, with positive patterns of HIV-1 and HIV-2 Western blots and a discrimination test positive for both viruses. As a whole, six (4.1%) of 147 HIV-positive sera showed either HIV-2 infection alone (n = 4) or dual reactivity. Of those, four were from Gabonese patients B, C, D, and E, and two were from immigrants from West Africa (patient A from Mali and patient F from Nigeria); two were female patients B and E. Among Gabonese patients, only one (patient E) had traveled to West Africa; the remaining three had never visited any neighboring country. However, one Gabonese man (patient C) lived in Port-Gentil, which has many West African immigrants. For all patients, the most likely risk factor for HIV was a heterosexual relationship with an unknown HIV-infected person. In three asymptomatic patients (A, B, and C) the HIV-2–serostatus was unexpected; in contrast, the three other patients had AIDS-related symptoms. Patients D and E had an HIV-2 Western blot pattern showing a marked decrease in anti-gag and pol reactivities compatible with their advanced stage of HIV-2 disease.

The case of a 55-year-old exclusively heterosexual asymptomatic woman (patient B) suggests the possibility of a specific variant of HIV-2 in Central Africa (2). The high frequency in primates in Gabon of natural infection with simian immunodeficiency retroviruses, which show a high degree of genetic relatedness to HIV-2 (3), could support such a hypothesis.

Two patients had typical dual reactivities to HIV-1 and HIV-2 antigens. To our knowledge, such dual reactivities have never been reported in Gabon (4). In the patient from Nigeria (patient F), the serologic pattern was typical of that usually observed in West Africa (5). Dual reactivity can result from genuine mixed infections and from serologic cross-reactivity in HIV-1 and HIV-2 infection alone; theoretically, it could also represent infection with a different, cross-reacting recombinant strain (5).

HIV-2 infection in Gabon is epidemiologically related to West Africa, because of cultural and, above all, economic ties. However, HIV-2 is not limited to immigrant populations from West Africa or to Gabonese citizens traveling in this area; it has also reached the indigenous Gabonese population. The possibility of rare cases of HIV-1 and HIV-2 coinfections, recombinant HIV-1 and HIV-2 strains, and also peculiar HIV-2 variants from Central Africa, should be considered in Gabon. A possible entry of HIV-2 infection into Central Africa from Gabon in the near future could have major public health implications.

Acknowledgments

We thank Dr. Jean Wickings for reviewing the manuscript. CIRMF is funded by the Gabonese government, ELF Gabon, and the French Ministry of Cooperation.

Carol Tevi-Benissan,* Madeleine Okome,† Maria Makuwa,* Moise Ndong Nkoume,† Joseph Lansoud-Soukate,* Alain Georges,* Marie-Claude Georges-Courbot,* and Laurent Belec‡

*Centre International de Recherches Medicales, Franceville, Gabon; †Fondation Jeanne Ebori, Libreville, Gabon; and ‡Centre Hospitalo-Universitaire Broussais, Paris, France.

References

  1. World Health Organization. Global programme on AIDS. Recommendations for the selection and use of HIV antibody tests. Wkly Epidemiol Rec 1992;67:145-9.
  2. Belec L, Martin PMV, Georges-Courbot MC, Brogan T, Gresenguet G, Mathiot CC, et al. Dementia as the primary manifestation of HIV-2 infection in a Central African patient. Ann Inst Pasteur Virol 1988;139:291-4.
  3. Georges-Courbot MC, Moisson P, Leroy E, Pingard AM, Nerrienet E, Dubreuil G, et al. Occurrence and frequency of transmission of naturally occurring simian retroviral infections (SIV, STLV, and SRV) at the CIRMF Primate Center, Gabon. J Med Primatol 1996;25:313-26.
  4. Delaporte E, Janssens W, Peeters M, Buve A, Dibanga G, Perret J-L, et al. Epidemiological and molecular characteristics of HIV infection in Gabon, 1986-1994. AIDS 1996;10:903-10.
  5. Peeters M, Gershy-Damet G-M, Fransen K, Koffi K, Coulibaly M, Delaporte E, et al. Virological and polymerase chain reactions studies of HIV-1/HIV-2 dual infection in Côte d'Ivoire. Lancet 1992;340:339-40.

Q Fever in French Guiana: New Trends

To the Editor: Q fever, the endemic disease caused by the rickettsial organism Coxiella burnetii, was first described in French Guiana in 1955 (1). Only sporadic cases were reported until 1996 when three patients were hospitalized in the intensive care unit of the Cayenne Hospital for acute respiratory distress syndrome. One of the patients died. Many cases of Q fever were diagnosed in the general population at the same time. A seroepidemiologic study was performed to determine whether the increase in cases was due to an increase in incidence or to an improvement in diagnosis. All paired samples of sera (acute-phase and convalescent-phase) from patients sent to the arbovirus laboratory for diagnosis of dengue infection from January 1, 1992, to December 31, 1996, were tested for antibodies to C. burnetii by immunofluorescence. All positive samples were also tested for immunoglobulin (IgM) by the same method; the IgG and IgM titers were determined by using a serial twofold dilution. A diagnosis of Q fever was made when there was a seroconversion from negative to positive or a twofold increase in IgG titer associated with the presence of IgM in the second sample.

One hundred and fifty-one of 426 paired sera collected between 1992 and 1996 were from patients recently infected with dengue fever. Twenty-five (9.1%) of 275 remaining sera were from Q fever patients. Significant differences were observed in the rates of Q fever in different years (p < 0.01); one (1.9%) of 53 was positive in 1992, five (9.1%) of 55 in 1993, five (8.6%) of 58 in 1994, three (4.8%) of 63 in 1995; a large increase was observed in 1996 (11 [23.9%] of 46). Differences by residence were also assessed. Rates of infection were higher in Cayenne (21 [13.0%] of 161) than in rural areas (4 [3.5%] of 114) (p < 0.01).

This study shows that cases of Q fever have occurred in French Guiana in recent years and that a significant increase in the incidence rate occurred in 1996. The reasons for this increase are unclear, and further studies of the epidemiology of Q fever in French Guiana are necessary. The epidemiology of Q fever is unusual in French Guiana because the rates of infection are much higher in Cayenne, the capital city, than in rural areas. No link with classical sources of infection (cattle, sheep, or goat birth products, or work in a slaughterhouse) was found. Indeed, Cayenne, with 80,000 inhabitants, is located near the Atlantic Ocean, and the prevailing winds blow from the sea. Airborne contamination from rural areas is therefore impossible. Furthermore, no large farm is in the immediate vicinity of the city. For identical reasons, contamination from the abattoirs is not likely; they are located on the west side of the city, near the Cayenne River, and the winds blow from the east. In our study, cases were almost equally distributed throughout the city, although many patients came from the same area.

A seroepidemiologic study to determine possible new sources of infection (e.g., dogs, cats) and estimate rates of seropositivity in cattle and sheep and a case-control study on new cases are being conducted.

F. Pfaff,* A. François,* D. Hommel,† I. Jeanne,* J. Margery,‡ G. Guillot,† Y. Couratte-Arnaude,‡ A. Hulin,† and A. Talarmin*
*Pasteur Institute of French Guiana, Cayenne, French Guiana; †Cayenne Hospital, Cayenne, French Guiana; and ‡Army Health Care Service, Cayenne, French Guiana

Reference

  1. Floch H. La pathologie vétérinaire en Guyane française (les affections des porcins, des caprins et des ovins). Revue Elev Méd Vét Pays Trop 1955;8:11-3.

Ixodes dammini: A Junior Synonym for Ixodes scapularis

To the Editor: The authors of "A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini" (1) provide useful information regarding a possibly new tick-borne encephalitis-like virus. However, the use of the name Ixodes dammini is not accurate for describing this species. I. dammini (Spielman, Clifford, Piesman, and Corwin) was synonymized with Ixodes scapularis (Say) in 1993 by Oliver et al. (2) and was redescribed in 1996 (3) to reduce confusion regarding identification. Keirans and colleagues summarize a wide array of rigorous studies involving hybridization, assortative mating, isozymes, and morphometrics, all of which provide evidence supporting the synonymization of the two tick species (3).

The synonymization of I. dammini with I. scapularis has been widely accepted. "I. scapularis (= I. dammini)" is still often used, but the use of I. scapularis as the sole nomen for this species is becoming more common (4). Oliver et al. (2) have established I. dammini as a junior subjective synonym of I. scapularis. If scientifically rigorous evidence exists justifying the reestablishment of the species name I. dammini, it must be published according to proper procedure. The proper nomenclature of any species, let alone one of such widespread notoriety and public health importance, is too important to be relegated to a footnote. Until such evidence is presented, the continued misuse of I. dammini serves only to confuse health-care providers, public health professionals, and lay persons.

On a secondary matter, on page 167 of the dispatch, the authors state that "I. (Pholeoixodes) cookei is a one-host tick that is only distantly related to I. dammini and only rarely feeds on humans or mice" (1). I. cookei is a three-host tick (D.E. Sonenshine, pers. comm.), as are all the members of the genus Ixodes.

Martin Sanders
Maryland Department of Health and Mental Hygiene, Baltimore, Maryland, USA

References

  1. Telford SR III, Armstrong PM, Katavolos P, Foppa I, Garcia ASO, Wilson ML, Spielman A. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis 1997;3:165-70.
  2. Oliver JH, Owsley MR, Hutcheson AM, James C, Chen W, Irby S, et al. Conspecificity of the ticks Ixodes scapularis and Ixodes dammini (Acari: Ixodidae). J Med Entomol 1993;30:54-63.
  3. Keirans JE, Hutcheson HJ, Durden LA, Klompen JSH. Ixodes scapularis (Acari: Ixodidae): redescription of all active stages, distribution, hosts, geographical variation, and medical and veterinary importance. J Med Entomol 1996;33:297-318.
  4. Centers for Disease Control and Prevention. Lyme disease—United States, 1996. MMWR Morb Mortal Wkly Rep 1997;46:531-5.

The Name Ixodes dammini Epidemiologically Justified

To the Editor: Although a large body of evidence has been interpreted as supporting conspecificity of the deer tick (Ixodes dammini) and the blacklegged tick (Ixodes scapularis), according to Chapter VI, Article 23 L of the International Code of Zoological Nomenclature (1), "A name that has been treated as a junior synonym may be used as the valid name of a taxon by an author who considers the synonymy to be erroneous...."

Current use of I. scapularis to refer to the vector of Lyme disease obscures important epidemiologic issues. One of the reasons for "sinking" I. dammini was to make it easier to diagnose Lyme disease in areas where the disease was thought to be nonendemic: "The belief that I. dammini does not occur south of Maryland and that I. scapularis is a separate and distinct species yet unproven as a natural vector of Lyme disease has caused delays in Lyme disease surveillance in the South. The general attitude among physicians and veterinarians has been that Lyme disease is not a problem in that area, although patients present clinical symptoms of it" (2). Recognizing and reporting Lyme disease in southern and southcentral states should not, however, depend on whether the two ticks are conspecific. Only peer-reviewed descriptions of human cases of Lyme disease, with appropriate documentation of the diagnoses, should be accepted as evidence. Few such reports exist, and the evidence does not convincingly support a conclusion that Lyme disease exists as an epidemic zoonosis in southern states (3). This is not to say that residents outside the well-established eastern United States zoonotic sites (the Northeast and upper Midwest) do not have symptoms that fit one or more aspects of the current Centers for Disease Control and Prevention/Council of State and Territorial Epidemiologists/Association of State and Territorial Public Health Laboratory Directors surveillance definition for Lyme disease. Lyme disease-like infections, mainly manifesting as erythema migrans and strongly associated with Lone Star tick (Amblyomma americanum) bites are commonly seen in southern and southcentral states, but Borrelia burgdorferi does not seem to be the etiologic agent (4).

Enzootic transmission of Lyme disease spirochetes among rodents and ticks had been documented in southern and southcentral states by the late 1980s (5-7). The question, however, is whether there is frequent zoonotic transmission. There are widespread southern U.S. enzootic cycles of Trypanosoma cruzi, but few autochthonous human Chagas disease cases seem to occur because the vectors (such as Triatoma sanguisuga) have behavioral traits that reduce their capacity to serve as zoonotic vectors (8). Nymphal I. scapularis apparently do not frequently bite humans (7,9), although adult ticks do. The major feature of Lyme disease epidemiology in the Northeast and in the upper Midwest, however, is transmission by nymphal I. dammini (10).

Whether the predilection of nymphal I. dammini to feed on humans is environmentally determined or is a heritable trait with undescribed genetic markers remains unexplored. Particular mitochondrial DNA haplotypes seem to be more characteristic of I. dammini (11,12), and the use of such typing methods may enhance future analyses of the vectorial capacity of these ticks. For example, one might test the hypothesis that nymphal ticks removed from residents of sites in coastal North Carolina through Georgia, where both kinds of ticks have been collected, represent only I. dammini. But, if it is "widely accepted" that no differences exist between the two ticks, such studies may never be done. Similarly, many may wrongly assume that Lyme disease, human babesiosis, and human granulocytic ehrlichiosis are, or will become, epidemic throughout virtually all of the eastern United States. An equally likely scenario is that these zoonoses may never become public health problems for more southerly states. For the moment, then, distinguishing tick populations that frequently bite humans from those that rarely do seems to be a rational use of nomenclature, particularly for public health officials.

Dr. Sanders is correct in pointing out that all Ixodes spp. are "three-host" ticks, although my intent in using the term "one-host" was to indicate that all stages of I. cookei tend to feed on the same kind of animal (sometimes a single animal, within burrows), usually woodchucks, skunks, or raccoons. I regret the confusion from my use of the acarologic term in a descriptive context.

Sam R. Telford III
Harvard School of Public Health, Boston, Massachusetts, USA

References

  1. International code of zoological nomenclature. 3rd ed. London: International Trust for Zoological Nomenclature; 1985.
  2. Oliver JH Jr, Owsley MR, Hutcheson HJ, James AM, Chen C, Irby WS, et al. Conspecificity of the ticks Ixodes scapularis and I. dammini (Acari: Ixodidae). J Med Entomol 1993;30:54-63.
  3. Barbour AG. Does Lyme disease occur in the South? A survey of emerging tickborne infections in the region. Am J Med Sci 1996;311:34-40.
  4. Campbell GL, Paul WS, Schriefer ME, Craven RB, Robbins KE, Dennis DT, et al. Epidemiologic and diagnostic studies of patients with suspected early Lyme disease, Missouri, 1990-1993. J Infect Dis 1995;172:470-80.
  5. Levine JF, Apperson CS, Nicholson WL. The occurrence of spirochetes in ixodid ticks in North Carolina. Journal of Entomological Science1989;24:594-602.
  6. Kocan AA, Mukolwe SW, Murphy GL, Barker RW, Kocan KM. Isolation of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) from Ixodes scapularis and Dermacentor albopictus ticks (Acari: Ixodidae) in Oklahoma. J Med Entomol 1992;29:630-3.
  7. Luckhart S, Mullen GR, Wright JC. Etiologic agent of Lyme disease, Borrelia burgdorferi, detected in ticks (Acari: Ixodidae) collected at a focus in Alabama. J Med Entomol 1991;28:652-7.
  8. Pung OJ, Banks CW, Jones DN, Krissinger MW. Trypanosoma cruzi in wild raccoons, opossums, and triatomine bugs in southeast Georgia, USA. J Parasitol 1995;81:324-6.
  9. Lavender DR, Oliver JH Jr. Ticks (Acari:Ixodidae) in Bulloch County, Georgia. J Med Entomol 1996;33:224-31.
  10. Spielman A, Wilson ML, Levine JF, Piesman J. Ecology of Ixodes dammini borne human babesiosis and Lyme disease. Annu Rev Entomol 1985;30:439-60.
  11. Rich SM, Caporale DA, Telford SR III, Kocher TD, Hartl DL, Spielman A, et al. Distribution of the Ixodes ricinus-like ticks of eastern North America. Proc Natl Acad Sci U S A 1995;92:6284-8.
  12. Norris DE, Klompen JSH, Keirans JE, Black WC IV. Population genetics of Ixodes scapularis (Acari:Ixodidae) based on mitochondrial 16S and 12S genes. J Med Entomol 1996;33:78-89. 996;33:78-89.

Ebola/Athens Revisited

To the Editor: After our hypothesis that the plague of Athens (430 B.C.– 425 B.C.) could have been caused by Ebola virus was published in this journal (1996;2:155-6), it was brought to our attention that this hypothesis had been previously entertained.

Gayle D. Scarrow had published a paper entitled "The Athenian Plague: A Possible Diagnosis" in The Ancient History Bulletin 2.1 (1988). Unfortunately, this had not come to our attention in our literature search, and therefore we assumed that we were the first to recognize the possibility. Clearly, Ms. Scarrow deserves credit for suggesting this first. Her arguments are compelling, even without the support of more recently available information and the observations advanced in our publication.

We believe an evolving knowledge base (e.g., the information about the Côte d'Ivoire outbreak where a protracted epidemic has been meticulously documented) will serve to enhance the credibility of the Ebola/Athens hypothesis.

P.E. Olson,* A.S. Benenson,† and E.N. Genovese†
*U.S. Navy Balboa Hospital, San Diego, California, USA; †San Diego State University,
San Diego, California, USA

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