- Email: [email protected]
Secondary syphilis simulating oral hairy leukoplakia
Case reports 749
J AM ACAD DERMATOL VOLUME 49, NUMBER 4
though oral antifungals have been used to treat noncutaneous T beigelii infections,13 little success has been made with systemic treatment of white piedra. The utility of treating a concomitant bacterial infection has yet to be established. Recurrences are common upon the discontinuation of treatment. We thank Rosemary Walsh and Michelle Peiffer of the Electron Microscope Facility for the Life Sciences in the Life Sciences Consortium & Biotechnology Institute for their preparation and interpretation of scanning electron microscopy specimens. REFERENCES 1. Hayat M, editor. Principles & techniques of SEM, biological applications. New York: Van Nostrand Reinhold Co; 1978. 2. Hayat M, editor. Principles & techniques of SEM, biological applications. 3rd ed. Boca Raton, (FL): CRC Press; 1989. 3. Beigel H. O genero Trichosporon. Rev Med Cir do Brasil 1930; 38:251-61. 4. Ellner KM, McBride ME, Kalter DC, Tschen JA, Wolf JE. White piedra: evidence for a synergistic infection. Br J Dermatol 1990; 123:355-63. 5. Kalter DC, Tschen JA, Cemoch PL, McBride ME, Sperber J, Bruce
6.
7.
8. 9.
10.
11.
12. 13.
S, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am Acad Dermatol 1986;14:982-93. Fischman O, Pires de Camargo Z, Meireles M. Genital white piedra: An emerging new fungal disease? Fifth International Conference on Mycoses, Pan American Health Organization, 1980. p. 70-6. Erer B, Galimberti M, Lucarelli G, Giardini C, Polchi P, Baronciani D, et al. Trichosporon beigelii: a life-threatening pathogen in immunocompromised hosts. Bone Marrow Transplant 2000;25:745-9. Fusaro RM, Miller NG. Onychomycosis caused by Trichosporon beigelii in the United States. J Am Acad Dermatol 1984;11:747-9. Kalter DC, Tschen JA, Cernoch PL, McBride ME, Sperber J, Bruce S, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am Acad Dermatol 1986;14:982-93. Rippon JW. Medical mycology, the pathogenic fungi and the pathogenic actinomycetes. Philadelphia: Saunders; 1982. p. 148-53. Shelley WB, Miller MA. Electron microscopy, histochemistry, and microbiology of bacterial adhesion in trichomycosis axillaris. J Am Acad Dermatol 1984;10:1005-14. Whiting DA. Structural abnormalities of the hair shaft. J Am Acad Dermatol 1987;16:1-25. Hajjeh RA, Bhimberg HM. Bloodstream infection due to Trichosporon beigelii in a burn patient: Case report and review of therapy. Clin Infect Dis 1995;20:913-6.
Secondary syphilis simulating oral hairy leukoplakia Christian Aquilina, MD, Roland Viraben, MD, and Philippe Denis, MD Toulouse, France We describe a case of secondary syphilis of the tongue in which the main clinical presentation of the disease was similar to oral hairy leukoplakia. In a man who was HIV seronegative, the first symptom was a dryness of the throat followed by a feeling of foreign body in the tongue. Lesions were painful without cutaneous manifestations of secondary syphilis. IgM–fluorescent treponemal antibody test and typical serologic parameters promptly led to the diagnosis of secondary syphilis. We initiated an appropriate antibiotic therapy using benzathine penicillin, which induced healing of the tongue lesions. The differential diagnosis of this lesion may include oral squamous carcinoma, leukoplakia, candidosis, lichen planus, and, especially, hairy oral leukoplakia. This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of hairy oral leukoplakia. Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of many diseases of the oral mucosa. (J Am Acad Dermatol 2003;49:749-51.)
From the Department of Dermatology and Sexually Transmitted Diseases, La Grave Hospital. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Christian Aquilina, MD, Hoˆpital La Grave, Place Lange, 31052 Toulouse Ce´dex, France. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/S0190-9622(03)00484-5
T
here are few reports of secondary syphilis presenting with isolated oral lesions. We describe a clinical case of leukoplakia of the tongue, in a man who was HIV seronegative, similar to hairy oral leukoplakia induced by secondary syphilis. This case demonstrates an unusual clinical manifestation of syphilis and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of many oral disorders.
750 Case reports
J AM ACAD DERMATOL OCTOBER 2003
Fig 1. Painful leukokeratotic lesions of lateral aspects of tongue.
CASE REPORT A 41-year-old man was referred by his dermatologist for white leukokeratosis lesions of the left and right lateral aspects of the tongue (Fig 1). The first symptom was a painful dryness of the throat followed by prompt development of lingual patches. The lesion on his tongue had been present for nearly 1 month. He was an opera singer and had trouble singing because the lesions were painful. Burning pain was also exacerbated by food. The patient had a history of sexual contact 8 months ago, followed by an ulceration of the anal mucous that spontaneously healed within 10 days. He was otherwise in good health and a nonsmoker. The lesions consisted of abnormal white thickening of the mucosa of the 2 lateral margins of the tongue, slightly raised and poorly demarcated, with a corrugated surface as is described in hairy oral leukoplakia lesions. Physical examination showed no other mucous membrane lesions or cutaneous manifestations. There was no cervical lymph node enlargement. The remainder of the clinical examination was normal. Antibodies against HIV-1 and HIV-2 were negative (enzymelinked immunosorbent assay, Western blot). Culture from lesions showed no bacterial or fungal growth. A biopsy specimen was taken from a plaque and demonstrated a dense inflammatory infiltrate composed of lymphocytes, plasmocytes, and neutrophils. The epithelial layers were hyperplasic with acanthosis, papillomatosis, and parakeratosis (Fig 2). No fungi were seen in preparations stained with periodic acid-Schiff. The serologic tests for syphilis were positive: VDRL 1:128; Treponema pallidum hemagglutination 1:20480; and IgM–fluorescent treponemal antibody–absorption. Dark-field microscopy was not done. Clinical data, histologic analysis of specimen from the lesions, and serologic tests for syphilis promptly led to the diagnosis of secondary syphilis. Physical examination showed that the lesions were the only symptom of secondary syphilis.
Fig 2. Dermal infiltration of plasmocytes in tongue lesions compatible with syphilitic infection. (Hematoxylineosin stain, original magnification ⫻ 100.)
Results of routine laboratory examinations (complete blood cell count and all blood chemistries) were within normal limits. He received 2.4 m U of penicillin G benzathine with complete resolution of lesions within 4 days. HIV serology remained negative after 6 months of follow up, and the quantitative values of syphilis serology were not modified at that time.
DISCUSSION Syphilis, “the great imitator,” is a spirochetal illness with a myriad of dermatologic and systemic manifestations. Oral lesions are a prominent feature in all stages of syphilis and may be the first manifestation of the disease.1 The lips are the most frequent site of extragenital primary syphilis chancres followed by the tongue, buccal mucosa, and oropharynx. In contrast with the oral lesions of firststage syphilis, oral lesions of secondary syphilis are typically painful and multiple2 and are accompanied by a concomitant cutaneous eruption. The oral lesions referred to as mucous patches are predominantly located on the tongue. Typically 2 types are described, slightly elevated type plaques and, occasionally, ulcerated types that are usually oval and covered with a white or gray pseudomembrane; less frequently, the palate may be involved with lesions described as painful, red, and firm plaques.3 Tonsil-
J AM ACAD DERMATOL VOLUME 49, NUMBER 4
lar lesions, especially unilateral and painless, have been reported in both first- and second-stage syphilis.4 These lesions may heal spontaneously but often recur during a period of months. The tertiary stage develops in approximately one third of untreated patients with syphilis, usually 5 to 10 years after the initial infection. Oral lesions occur most commonly during this stage and are characterized by a chronic interstitial glossitis. Our observation is remarkable for the lack of cutaneous symptoms and the probable spread of the disease to the throat and the larynx, accounting for the hoarse voice. There are few reports of secondary syphilis in the literature presenting with isolated oral lesions.4-7 The histologic characteristics of secondary syphilis are as variable as the lesions. Although the changes are often nonspecific, findings of endothelial cell swelling, perivascular infiltrates with a preponderance of plasma cells, and epidermal psoriasiform hyperplasia support the diagnosis of syphilis.8 Another remarkable point of our observation is the near perfect similarity with hairy oral leukoplakia. This oral disease is a characteristic lesion presumably secondary to Epstein-Barr virus reactivation, frequently seen in individuals infected with HIV and less often in other individuals who are immunosuppressed. Our patient was seronegative for HIV at the time of the tongue lesion and 6 months later.9 This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of oral lesions resembling hairy oral leukoplakia. This highlights the need for routine serologic testing for syphilis in all cases of hairy oral leukoplakia, particularly in patients with HIV infection.10,11 Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of diseases of the oral mucosa such as oral squamous cell carcinoma, leukoplakia, erythroleukoplakia, candidosis, lichen planus, and granulomatous diseases.1,12 Another imitation of
Case reports 751
syphilis is carcinoma of the tongue: Dickenson et al12 demonstrated that 5 of 63 patients (8%) who presented with neoplasms of the tongue reacted to syphilis antibodies. With this unusual type similar to hairy oral leukoplakia, as in our observation, the diagnosis is probably often overlooked and clinicians must be familiar with protean manifestations of syphilis. This emphasizes the need for care in diagnosing the “great imitator,” first because of the resurgence of syphilis in the HIV era, and second because syphilis significantly increases HIV risk.13 REFERENCES 1. De Swaan B, Tjiam KH, Vuzevski VD, Van Joost T, Stolz E. Solitary oral condylomata lata in a patient with secondary syphilis. Sex Transm Dis 1985;12:238-40. 2. Junkins-Hopkins JM. Multiple painful oral ulcerations: secondary syphilis. Arch Dermatol 1995;131:833-6. 3. Ban M, Ohtani M, Seishima M. A case of secondary syphilis with mucous patches on the hard palate. J Dermatol 1995;22:52-4. 4. Shimizu T, Shinogi J, Majima Y, Sakakura Y. Secondary syphilis of the tonsil. Arch Otorhinolaryngol 1989;246:117-20. 5. Mani NJ. Secondary syphilis initially diagnosed from oral lesions. Oral Surg 1984;58:47-50. 6. Fiumara NJ, Grande DJ, Giunta JL. Papular secondary syphilis of the tongue. Oral Surg 1978;45:540-2. 7. Manton SL, Egglestone SI, Alexander I, Scully C. Oral presentation of secondary syphilis. Br Dent J 1986;160:237-8. 8. Pandhi RK, Slingh N, Ranam M. Secondary syphilis: a clinicopathologic study. Int J Dermatol 1995;34:240-3. 9. Wurapa AK, Luque AE, Menegus MA. Oral hairy leukoplakia: a manifestation of primary infection with Epstein-Barr-virus? Scand J Infect Dis 1999;31:505-6. 10. Ficarra G, Zaragoza AM, Stendardi L, Parri F, Cockerell CJ. Early oral presentation of lues maligna in a patient with HIV infection: a case report. Oral Surg Oral Med Oral Pathol 1993;75:728-32. 11. Ramirez-Amador V, Madero JG, Pedraza LE, de la Rosa Garcia E, Guevara MG, Gutierrez ER, et al. Oral secondary syphilis in a patient with human immunodeficiency virus infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:652-4. 12. Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg 1995;33:319-20. 13. Sellati TJ, Wilkinson DA, Sheffield JS, Koup RA, Radolf JD, Norgard MV. Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1. J Infect Dis 2000;181:283-93.
J AM ACAD DERMATOL VOLUME 49, NUMBER 4
though oral antifungals have been used to treat noncutaneous T beigelii infections,13 little success has been made with systemic treatment of white piedra. The utility of treating a concomitant bacterial infection has yet to be established. Recurrences are common upon the discontinuation of treatment. We thank Rosemary Walsh and Michelle Peiffer of the Electron Microscope Facility for the Life Sciences in the Life Sciences Consortium & Biotechnology Institute for their preparation and interpretation of scanning electron microscopy specimens. REFERENCES 1. Hayat M, editor. Principles & techniques of SEM, biological applications. New York: Van Nostrand Reinhold Co; 1978. 2. Hayat M, editor. Principles & techniques of SEM, biological applications. 3rd ed. Boca Raton, (FL): CRC Press; 1989. 3. Beigel H. O genero Trichosporon. Rev Med Cir do Brasil 1930; 38:251-61. 4. Ellner KM, McBride ME, Kalter DC, Tschen JA, Wolf JE. White piedra: evidence for a synergistic infection. Br J Dermatol 1990; 123:355-63. 5. Kalter DC, Tschen JA, Cemoch PL, McBride ME, Sperber J, Bruce
6.
7.
8. 9.
10.
11.
12. 13.
S, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am Acad Dermatol 1986;14:982-93. Fischman O, Pires de Camargo Z, Meireles M. Genital white piedra: An emerging new fungal disease? Fifth International Conference on Mycoses, Pan American Health Organization, 1980. p. 70-6. Erer B, Galimberti M, Lucarelli G, Giardini C, Polchi P, Baronciani D, et al. Trichosporon beigelii: a life-threatening pathogen in immunocompromised hosts. Bone Marrow Transplant 2000;25:745-9. Fusaro RM, Miller NG. Onychomycosis caused by Trichosporon beigelii in the United States. J Am Acad Dermatol 1984;11:747-9. Kalter DC, Tschen JA, Cernoch PL, McBride ME, Sperber J, Bruce S, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am Acad Dermatol 1986;14:982-93. Rippon JW. Medical mycology, the pathogenic fungi and the pathogenic actinomycetes. Philadelphia: Saunders; 1982. p. 148-53. Shelley WB, Miller MA. Electron microscopy, histochemistry, and microbiology of bacterial adhesion in trichomycosis axillaris. J Am Acad Dermatol 1984;10:1005-14. Whiting DA. Structural abnormalities of the hair shaft. J Am Acad Dermatol 1987;16:1-25. Hajjeh RA, Bhimberg HM. Bloodstream infection due to Trichosporon beigelii in a burn patient: Case report and review of therapy. Clin Infect Dis 1995;20:913-6.
Secondary syphilis simulating oral hairy leukoplakia Christian Aquilina, MD, Roland Viraben, MD, and Philippe Denis, MD Toulouse, France We describe a case of secondary syphilis of the tongue in which the main clinical presentation of the disease was similar to oral hairy leukoplakia. In a man who was HIV seronegative, the first symptom was a dryness of the throat followed by a feeling of foreign body in the tongue. Lesions were painful without cutaneous manifestations of secondary syphilis. IgM–fluorescent treponemal antibody test and typical serologic parameters promptly led to the diagnosis of secondary syphilis. We initiated an appropriate antibiotic therapy using benzathine penicillin, which induced healing of the tongue lesions. The differential diagnosis of this lesion may include oral squamous carcinoma, leukoplakia, candidosis, lichen planus, and, especially, hairy oral leukoplakia. This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of hairy oral leukoplakia. Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of many diseases of the oral mucosa. (J Am Acad Dermatol 2003;49:749-51.)
From the Department of Dermatology and Sexually Transmitted Diseases, La Grave Hospital. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Christian Aquilina, MD, Hoˆpital La Grave, Place Lange, 31052 Toulouse Ce´dex, France. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/S0190-9622(03)00484-5
T
here are few reports of secondary syphilis presenting with isolated oral lesions. We describe a clinical case of leukoplakia of the tongue, in a man who was HIV seronegative, similar to hairy oral leukoplakia induced by secondary syphilis. This case demonstrates an unusual clinical manifestation of syphilis and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of many oral disorders.
750 Case reports
J AM ACAD DERMATOL OCTOBER 2003
Fig 1. Painful leukokeratotic lesions of lateral aspects of tongue.
CASE REPORT A 41-year-old man was referred by his dermatologist for white leukokeratosis lesions of the left and right lateral aspects of the tongue (Fig 1). The first symptom was a painful dryness of the throat followed by prompt development of lingual patches. The lesion on his tongue had been present for nearly 1 month. He was an opera singer and had trouble singing because the lesions were painful. Burning pain was also exacerbated by food. The patient had a history of sexual contact 8 months ago, followed by an ulceration of the anal mucous that spontaneously healed within 10 days. He was otherwise in good health and a nonsmoker. The lesions consisted of abnormal white thickening of the mucosa of the 2 lateral margins of the tongue, slightly raised and poorly demarcated, with a corrugated surface as is described in hairy oral leukoplakia lesions. Physical examination showed no other mucous membrane lesions or cutaneous manifestations. There was no cervical lymph node enlargement. The remainder of the clinical examination was normal. Antibodies against HIV-1 and HIV-2 were negative (enzymelinked immunosorbent assay, Western blot). Culture from lesions showed no bacterial or fungal growth. A biopsy specimen was taken from a plaque and demonstrated a dense inflammatory infiltrate composed of lymphocytes, plasmocytes, and neutrophils. The epithelial layers were hyperplasic with acanthosis, papillomatosis, and parakeratosis (Fig 2). No fungi were seen in preparations stained with periodic acid-Schiff. The serologic tests for syphilis were positive: VDRL 1:128; Treponema pallidum hemagglutination 1:20480; and IgM–fluorescent treponemal antibody–absorption. Dark-field microscopy was not done. Clinical data, histologic analysis of specimen from the lesions, and serologic tests for syphilis promptly led to the diagnosis of secondary syphilis. Physical examination showed that the lesions were the only symptom of secondary syphilis.
Fig 2. Dermal infiltration of plasmocytes in tongue lesions compatible with syphilitic infection. (Hematoxylineosin stain, original magnification ⫻ 100.)
Results of routine laboratory examinations (complete blood cell count and all blood chemistries) were within normal limits. He received 2.4 m U of penicillin G benzathine with complete resolution of lesions within 4 days. HIV serology remained negative after 6 months of follow up, and the quantitative values of syphilis serology were not modified at that time.
DISCUSSION Syphilis, “the great imitator,” is a spirochetal illness with a myriad of dermatologic and systemic manifestations. Oral lesions are a prominent feature in all stages of syphilis and may be the first manifestation of the disease.1 The lips are the most frequent site of extragenital primary syphilis chancres followed by the tongue, buccal mucosa, and oropharynx. In contrast with the oral lesions of firststage syphilis, oral lesions of secondary syphilis are typically painful and multiple2 and are accompanied by a concomitant cutaneous eruption. The oral lesions referred to as mucous patches are predominantly located on the tongue. Typically 2 types are described, slightly elevated type plaques and, occasionally, ulcerated types that are usually oval and covered with a white or gray pseudomembrane; less frequently, the palate may be involved with lesions described as painful, red, and firm plaques.3 Tonsil-
J AM ACAD DERMATOL VOLUME 49, NUMBER 4
lar lesions, especially unilateral and painless, have been reported in both first- and second-stage syphilis.4 These lesions may heal spontaneously but often recur during a period of months. The tertiary stage develops in approximately one third of untreated patients with syphilis, usually 5 to 10 years after the initial infection. Oral lesions occur most commonly during this stage and are characterized by a chronic interstitial glossitis. Our observation is remarkable for the lack of cutaneous symptoms and the probable spread of the disease to the throat and the larynx, accounting for the hoarse voice. There are few reports of secondary syphilis in the literature presenting with isolated oral lesions.4-7 The histologic characteristics of secondary syphilis are as variable as the lesions. Although the changes are often nonspecific, findings of endothelial cell swelling, perivascular infiltrates with a preponderance of plasma cells, and epidermal psoriasiform hyperplasia support the diagnosis of syphilis.8 Another remarkable point of our observation is the near perfect similarity with hairy oral leukoplakia. This oral disease is a characteristic lesion presumably secondary to Epstein-Barr virus reactivation, frequently seen in individuals infected with HIV and less often in other individuals who are immunosuppressed. Our patient was seronegative for HIV at the time of the tongue lesion and 6 months later.9 This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of oral lesions resembling hairy oral leukoplakia. This highlights the need for routine serologic testing for syphilis in all cases of hairy oral leukoplakia, particularly in patients with HIV infection.10,11 Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of diseases of the oral mucosa such as oral squamous cell carcinoma, leukoplakia, erythroleukoplakia, candidosis, lichen planus, and granulomatous diseases.1,12 Another imitation of
Case reports 751
syphilis is carcinoma of the tongue: Dickenson et al12 demonstrated that 5 of 63 patients (8%) who presented with neoplasms of the tongue reacted to syphilis antibodies. With this unusual type similar to hairy oral leukoplakia, as in our observation, the diagnosis is probably often overlooked and clinicians must be familiar with protean manifestations of syphilis. This emphasizes the need for care in diagnosing the “great imitator,” first because of the resurgence of syphilis in the HIV era, and second because syphilis significantly increases HIV risk.13 REFERENCES 1. De Swaan B, Tjiam KH, Vuzevski VD, Van Joost T, Stolz E. Solitary oral condylomata lata in a patient with secondary syphilis. Sex Transm Dis 1985;12:238-40. 2. Junkins-Hopkins JM. Multiple painful oral ulcerations: secondary syphilis. Arch Dermatol 1995;131:833-6. 3. Ban M, Ohtani M, Seishima M. A case of secondary syphilis with mucous patches on the hard palate. J Dermatol 1995;22:52-4. 4. Shimizu T, Shinogi J, Majima Y, Sakakura Y. Secondary syphilis of the tonsil. Arch Otorhinolaryngol 1989;246:117-20. 5. Mani NJ. Secondary syphilis initially diagnosed from oral lesions. Oral Surg 1984;58:47-50. 6. Fiumara NJ, Grande DJ, Giunta JL. Papular secondary syphilis of the tongue. Oral Surg 1978;45:540-2. 7. Manton SL, Egglestone SI, Alexander I, Scully C. Oral presentation of secondary syphilis. Br Dent J 1986;160:237-8. 8. Pandhi RK, Slingh N, Ranam M. Secondary syphilis: a clinicopathologic study. Int J Dermatol 1995;34:240-3. 9. Wurapa AK, Luque AE, Menegus MA. Oral hairy leukoplakia: a manifestation of primary infection with Epstein-Barr-virus? Scand J Infect Dis 1999;31:505-6. 10. Ficarra G, Zaragoza AM, Stendardi L, Parri F, Cockerell CJ. Early oral presentation of lues maligna in a patient with HIV infection: a case report. Oral Surg Oral Med Oral Pathol 1993;75:728-32. 11. Ramirez-Amador V, Madero JG, Pedraza LE, de la Rosa Garcia E, Guevara MG, Gutierrez ER, et al. Oral secondary syphilis in a patient with human immunodeficiency virus infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:652-4. 12. Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg 1995;33:319-20. 13. Sellati TJ, Wilkinson DA, Sheffield JS, Koup RA, Radolf JD, Norgard MV. Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1. J Infect Dis 2000;181:283-93.