382
Influenza-related excess mortality in the Netherlands 1989/90 SIR,—The number of weekly influenza-like illnesses, as reported by general practitioners randomly distributed over the Netherlands, started to increase at the beginning of December, 1989, and reached a peak of 54 per 10 000 inhabitants around Christmas. This pattern resembles that experienced in 1988/89 and in earlier epidemics (fig 1).Unexpectedly the Netherlands Central Bureau of Statistics recorded a considerable increase in total mortality in December, 1989, and January, 1990.’ The daily number of deaths rose from the expected mean of 370 (in the total population) to over 400 during the influenza period and reached 500 in the second week of January (fig 2). Mortality in these 2 months rose by 18%, the increase being most pronounced in people over 80 years old (26%). The excess deaths totalled 4100 (0-3 per 1000 population). In the winters of 1988/89 and 1987/88 no excess mortality was registered. An unexpected excess mortality of 0-5 per 1000 has also been reported in the UK,z where it was associated with influenza.
epidemic of 1989/90 were tested simultaneously against vaccine strain A/Shanghai/11/87(H3N2) and against two strains isolated during the two epidemics in the Netherlands. Protection was more prevalent before the latest epidemic than it was before the epidemic of 1988/89:
Thus in 1989/90 moderate influenza rates were attended by unusually high mortality, an observation that cannot be explained by a major antigenic drift or by lack of antibody. We suggest a change in biological activity5 as the cause. We thank C. J. M. Prins, Central Bureau of Statistics, for his advice, and G. L. van de Water for technical assistance.
MARC J. W. SPRENGER ROB J. A. DIEPERSLOOT WALTER E. P. BEYER NIC MASUREL
Department of Virology and WHO Influenza Centre, Erasmus University Rotterdam, 3000DR Rotterdam, Netherlands
1 Prins CJM. Many influenza deaths at the turn of the year Mon Stat Popul 1990, 38: 8-9. 2. Curwen M, Dunnell K, Ashley J Hidden influenza deaths Br Med J 1990, 300: 896 3. Sprenger MJW, Diepersloot RJA, Stuiver M, Postema CA, Masurel N. Influenza 1989/’90: A-H3N2-virus related to vaccine-virus. Ned Tijdschr Geneesk 1990; 134: 663-64. 4. Zuckerman M, Oxford J, Wood J, Taylor J. Influenza A (H3N2) component of recommended vaccine induces antibody to current virus. Lancet 1990, 335: 179-80 5. Culliton BJ. Emerging viruses, emerging threat. Science 1990; 247: 279-80. 6 Masurel N, Laufer J. A one-year study of trivalent influenza vaccines in primed or unprimed volunteers immunogenicity, clinical reactions and protection J Hyg
1984, 92: 263-76.
Ventricular arrhythmia in secondary
syphilis
Fig 1-lnfluenza-like illness
per 10000 inhabitants per week in
the Netherlands.
Line = 1988/89, bar =1989/90 Horizontal
axis
shows winter week
numbers 42 to 4
The predominant influenza strain throughout the 1989/80 epidemic was A/Shanghai/ll/87(H3N2)-like. Haemagglutinin3 and neuraminidase antigenic make-ups demonstrate that this strain is almost identical to the vaccine strain4 and the epidemic strain of
1988/89. Sera of 100 inhabitants, selected at random, and collected before the epidemic of 1988/89 and another 100 found before the
Fig 2-Deaths
per
month,
Netherlands. Horizontal lines=annual averages
seasonally adjusted,
in
the
SIR,-An upsurge in the incidence of congenital, primary, and secondary syphilis, the great imitator, has been reported lately.’,2 In his 1934 treatise on syphilis, Stokes3 noted that despite evidence of myocardial invasion by Treponema pallidum the "manifestations of this involvement are among the rarities of experience with early syphilis". We describe ventricular arrhythmias in a previously healthy young woman with secondary syphilis. A 33-year-old woman with an unremarkable medical history presented with a febrile illness characterised initially by a truncal, non-pruritic, non-scaly, papular rash. After five days she had intermittent palpitations associated with shortness of breath and dizziness without chest pain or syncope. Although her examination and electrocardiogram (ECG) were unremarkable, a Holter monitor demonstrated non-sustained polymorphic ventricular tachycardia with 4-5 beat runs (heart rate 225 beats per minute), frequent couplets, and premature ventricular contractions (over 10 per minute), prompting her admission. She had no abnormalities other than the rash. Evaluation included normal blood counts, serum electrolytes, creatinine, liver function tests, ECG, and chest radiograph. Sedimentation rate was 60 mm/h, and rheumatoid factor, antinuclear antibodies, HIV-1, cytomegalovirus, EpsteinBarr virus" and anti-streptolysin 0 antibodies were negative. During the first 48 h she continued to have symptomatic episodes of non-sustained ventricular tachycardia. She had normal signalaveraged ECG, cardiac echocardiogram, exercise tolerance test, and stress regional myocardial perfusion study. Her ventricular tachycardia resolved spontaneously. When a sore throat and axillary and cervical adenopathy developed and the rash spread to her limbs, palms, and soles, VDRL (titre 16) and FTA (positive) tests were done. Skin biopsy showed dermal perivascular lymphoplasmacytic infiltrates with endothelial prominence typical of secondary syphilis, but spirochaetes were not identified by Steiner’s stain. She was treated for secondary syphilis with 2-4 MU of intramuscular benzathine penicillin with resolution of her symptoms. Her husband also had a reactive VDRL and FTA.
383
months after infection the widespread lymphatic dissemination of T pallidum is haematogenous marked by a variable presentation including low-grade fevers, malaise, sore throat, headache, adenopathy, and a rash.’ Tissue invasion by the organism is probably responsible for most of these early manifestations although circulating immune complexes may play a part, especially in the nephropathy of secondary syphilis.4.5 Various non-specific pathological fmdings in the myocardium such as lymphocytic and plasma-cell infiltration with secondary myocardial cell injury and obliterative endarteritis leading to fibrosis have been attributed to syphilis, although this has been widely debated.6 Ventricular tachycardia and extrasystoles have been associated with acute myocarditis of other infectious causes.7.8* Early 20th century workers described arrhythmias with secondary syphilis, but this association is not made in contemporary reports.9 Although the precise cause of ventricular arrythmias cannot be established, the temporal relation with secondary syphilis raises the possibility of syphilitic myocarditis. The wide spectrum of illnesses caused by T pallidum coupled with the growing frequency of the disease behoves doctors to have a high index of suspicion.
Several weeks
to
and
PAUL BECHERER DAVID GUTSCH JANET FISCHER
University of North Carolina, Chapel Hill, North Carolina 27599, USA 1 Center for Disease Control
Congenital syphilis: New York City, 1986-1988. MMWR
1989, 38: 825-29. 2 Andrus
JK, Fleming DW, Harger DR, et al. Partner notification: can it control epidemic syphilis? Ann Intern Med 1990; 112: 539-43. Stokes JH Modem clinical syphilology, 2nd ed Philadelphia: W B Saunders, 1934. Gamble CN, Reardan JB Immunopathogenesis of syphilitic glomerulonephritis elution of antitreponemal antibody from glomerular immune complex deposits. N Engl J Med 1975, 292: 449-54 Turner T, Hardy P, Newman B. Infectivity tests in syphilis. Br J Vener Dis 1969, 45:
3 4
5
183-96. 6 Saphir O Syphilitic myocarditis Arch Pathol 1932, 13: 266-95. 7 Vikerfors T, Stjerna A, Olcen P, Malmcrona R, Magnius L Acute myocarditis. Acta
Med Scand 1988; 223: 45-52
Karjalainen J, Viitasals M, Kala R, Heikkila J. 24-hour electrocardiographic recordings in mild acute infectious myocarditis. Ann Clin Res 1984; 16: 34-39. Anders JM. Certain syphilitic affections of the heart and aorta. Am J Med Sci 1915,
8 9
150: 835-42
Co-infection with HTLV-I/II and HIV-1 SIR,-Dr Page and colleagues (June 16,
p
1439)
assert
that
HTLV-I/II seropositivity adversely affects the clinical outcome for HIV-1 seropositive intravenous drug users. However, the method used to measure anti-HTLV-I/ IIcalls into question the validity of their fmdings. By measuring antibodies to p24 antigen only Page et al have not met the criterion for seropositivity that antibodies against bothgag and env gene products be demonstrated.Although an assay based on p24 antigen is likely to detect antibodies against both HTLV-1 and HTLV-11, the sensitivity and specificity of the assay used are not given. False-positive results will be generated by an assay based on gag antigen alone: rates up to 10% have been reported in a range of assays2 and use of p24 based immunoassays has previously been associated with a high degree of non-specificity for HTLV-1 infectionFurthermore, confirmation by an independent method is essential. Even when several screening assays have been used, confirmation is difficult. Western blot assays are not reliable because env encoded glycoproteins are poorly transferred to nitrocellulose, and a radioimmunoprecipitation assay is often needed. Virus Reference Laboratory, Central Public Health Laboratory, London NW9 5HT, UK
JENNIFER H. C. TOSSWILL
Infectious Diseases Unit, Department of Medicine,
Royal Postgraduate
Medical School,
London W12 1 US Public Health Service Working
Group Licensure of screening tests for antibody human T-lymphotropic virus type I MMWR 1988; 37: 736-47 Weber JN, Banatvala N, Clayden S, et al HTLV-I infection in Papua New Guinea. evidence for serologic false positivity J Infect Dis 1989, 159: 1025-28 Koprowski H, DeFreitas EC, Harper ME, et al Multiple sclerosis and human T-cell lymphotropic retroviruses Nature 1985; 318: 154-60 to
2
3
JONATHAN N. WEBER
SIR,-Dr Page and colleagues report that dual infection with affects survival in HIV-1-positive intravenous drug users, supporting findings in homosexual men.’ They suppose that carriage of HTLV-I/II, which suppresses cell-mediated immunity,2 compounds the immunosuppression due to HIV, thereby accelerating disease progression. Although this is a plausible argument recent observations on the biology of these
HTLV-I/II adversely
retroviruses
provide attractive alternatives.
HTLV-I/III code for two trans-acting regulatory proteins tax and rex,3 which are expressed at low levels in carriers of HTLV-I.4 HTLV-1 tax can activate cellular genes which may be involved in the synergistic effect. These include up-regulation of interleukin-2 (IL-2), IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor (GM-CSF); and down-regulation of the expression of human &bgr;-polymerase, a cellular enzyme involved in host cell repair.5 Furthermore, the HTLV-I tax product stimulates the HIV-1 enhancer besides its own enhancerthereby amplifying viral gene expression, which could accelerate disease progression in HIV-1. The tax product may influence T-cell proliferation through induction of both IL-2 and its receptor, activating and accelerating production of HIV-1 virions resulting in T cell death. Upregulation of cytokine GM-CSF by the HTLV-I/II tax product may also accelerate progression by enhancing HIV-1 replication in monocytes.8 The HTLV-IjII rex product is required for viral replication; however, it can functionally replace the HIV-1 rev product and rescue replication of a rev deficient HIV-1 provirus.9 This complementation may further augment disease progression. Department of Haematological Medicine, King’s College School of Medicine and Dentistry, London SE5 9PJ, UK
A. PAGLIUCA G. J. MUFTI
1 Bartholomew C, Blattner W, Cleghorn F. Progression to AIDS in homosexual men co-infected with HIV and HTLV-I in Trinidad. Lancet 1987, ii: 1469 2. Imai J, Hinuma Y. Epstein-Barr virus specific antibodies in patients with adult T-cell leukemia and healthy ATLV-carriers. Int J Cancer 1983; 31: 197-200. 3. Rosenblatt JD, Chen ISY, Wachsman W. Infection with HTLV-I and HTLV-II: evolving concepts Semin Hematol 1988; 25: 230-46. 4. Kinishita T, Shimoyama M, Tobinai K, et al. Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci USA 1989, 86: 5620-24. 5. Jeang KT, Widen SG, Semmes OJ, Wilson SH. HTLV-I trans-activator protein, tax, is a transrepressor of the human &bgr;-polymerase gene Science 1990; 247: 1082-84. 6. Bohnlein E, Siekevitz M, Ballard DW, et al Stimulation of the human immunodeficiency virus type I enhancer by the human T cell leukaemia virus type I tax gene product involves the action of inducible cellular proteins J Virol 1989; 63: 1578-86. 7 Nimer SD, Gasson JC, Hu K, et al. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene 1989; 4: 671-76. 8. Koyanagi Y, O’Bnen WA, Zhao JQ, Golde DW, Gasson JC, Chen ISY. Cytokines alter production of HIV-I from primary mononuclear phagocytes. Science 1988; 241: 1673-75. 9. Rimsky L, Hauber J, Dukovich M, et al. Functional replacement of the HIV-I rev protein by the HTLV-I rex protein. Nature 1988, 335: 738-40.
Unusual
cause
of
pharyngeal ulcerations
in
AIDS SIR,-Dr Gorin and colleagues (June 2, p 1343) report successful thalidomide therapy in hyperalgic pharyngeal ulcerations of AIDS, as described previously.’ We also have experience of such ulcerations. Pneumocystis carinii pneumonia was diagnosed in a 34-year-old homosexual man in 1986. Soon after, he was admitted with co-trimoxazole-induced neutropenia and Escherichia cola septicaemia. In 1987 the patient was treated with zidovudine and pentamidine aerosol. Thereafter, nine episodes of painful pharyngeal ulcerations occurred over 2 years, often with neutropenia not related to zidovudine. The ulcerations were unilateral and led to complete destruction of the right pharyngeal wall. While all microbiological samples remained sterile, treatment with parenteral amphotericin B and broad-spectrum antibiotics was effective. Thalidomide was given as prophylaxis for the ulcerations but they recurred. Although daily fluconazole was given, early in 1989 pulmonary infiltrates and an abscess with cavity due to mucor (Abszdia coryrnbifera was found in both sputum and
Influenza-related excess mortality in the Netherlands 1989/90 SIR,—The number of weekly influenza-like illnesses, as reported by general practitioners randomly distributed over the Netherlands, started to increase at the beginning of December, 1989, and reached a peak of 54 per 10 000 inhabitants around Christmas. This pattern resembles that experienced in 1988/89 and in earlier epidemics (fig 1).Unexpectedly the Netherlands Central Bureau of Statistics recorded a considerable increase in total mortality in December, 1989, and January, 1990.’ The daily number of deaths rose from the expected mean of 370 (in the total population) to over 400 during the influenza period and reached 500 in the second week of January (fig 2). Mortality in these 2 months rose by 18%, the increase being most pronounced in people over 80 years old (26%). The excess deaths totalled 4100 (0-3 per 1000 population). In the winters of 1988/89 and 1987/88 no excess mortality was registered. An unexpected excess mortality of 0-5 per 1000 has also been reported in the UK,z where it was associated with influenza.
epidemic of 1989/90 were tested simultaneously against vaccine strain A/Shanghai/11/87(H3N2) and against two strains isolated during the two epidemics in the Netherlands. Protection was more prevalent before the latest epidemic than it was before the epidemic of 1988/89:
Thus in 1989/90 moderate influenza rates were attended by unusually high mortality, an observation that cannot be explained by a major antigenic drift or by lack of antibody. We suggest a change in biological activity5 as the cause. We thank C. J. M. Prins, Central Bureau of Statistics, for his advice, and G. L. van de Water for technical assistance.
MARC J. W. SPRENGER ROB J. A. DIEPERSLOOT WALTER E. P. BEYER NIC MASUREL
Department of Virology and WHO Influenza Centre, Erasmus University Rotterdam, 3000DR Rotterdam, Netherlands
1 Prins CJM. Many influenza deaths at the turn of the year Mon Stat Popul 1990, 38: 8-9. 2. Curwen M, Dunnell K, Ashley J Hidden influenza deaths Br Med J 1990, 300: 896 3. Sprenger MJW, Diepersloot RJA, Stuiver M, Postema CA, Masurel N. Influenza 1989/’90: A-H3N2-virus related to vaccine-virus. Ned Tijdschr Geneesk 1990; 134: 663-64. 4. Zuckerman M, Oxford J, Wood J, Taylor J. Influenza A (H3N2) component of recommended vaccine induces antibody to current virus. Lancet 1990, 335: 179-80 5. Culliton BJ. Emerging viruses, emerging threat. Science 1990; 247: 279-80. 6 Masurel N, Laufer J. A one-year study of trivalent influenza vaccines in primed or unprimed volunteers immunogenicity, clinical reactions and protection J Hyg
1984, 92: 263-76.
Ventricular arrhythmia in secondary
syphilis
Fig 1-lnfluenza-like illness
per 10000 inhabitants per week in
the Netherlands.
Line = 1988/89, bar =1989/90 Horizontal
axis
shows winter week
numbers 42 to 4
The predominant influenza strain throughout the 1989/80 epidemic was A/Shanghai/ll/87(H3N2)-like. Haemagglutinin3 and neuraminidase antigenic make-ups demonstrate that this strain is almost identical to the vaccine strain4 and the epidemic strain of
1988/89. Sera of 100 inhabitants, selected at random, and collected before the epidemic of 1988/89 and another 100 found before the
Fig 2-Deaths
per
month,
Netherlands. Horizontal lines=annual averages
seasonally adjusted,
in
the
SIR,-An upsurge in the incidence of congenital, primary, and secondary syphilis, the great imitator, has been reported lately.’,2 In his 1934 treatise on syphilis, Stokes3 noted that despite evidence of myocardial invasion by Treponema pallidum the "manifestations of this involvement are among the rarities of experience with early syphilis". We describe ventricular arrhythmias in a previously healthy young woman with secondary syphilis. A 33-year-old woman with an unremarkable medical history presented with a febrile illness characterised initially by a truncal, non-pruritic, non-scaly, papular rash. After five days she had intermittent palpitations associated with shortness of breath and dizziness without chest pain or syncope. Although her examination and electrocardiogram (ECG) were unremarkable, a Holter monitor demonstrated non-sustained polymorphic ventricular tachycardia with 4-5 beat runs (heart rate 225 beats per minute), frequent couplets, and premature ventricular contractions (over 10 per minute), prompting her admission. She had no abnormalities other than the rash. Evaluation included normal blood counts, serum electrolytes, creatinine, liver function tests, ECG, and chest radiograph. Sedimentation rate was 60 mm/h, and rheumatoid factor, antinuclear antibodies, HIV-1, cytomegalovirus, EpsteinBarr virus" and anti-streptolysin 0 antibodies were negative. During the first 48 h she continued to have symptomatic episodes of non-sustained ventricular tachycardia. She had normal signalaveraged ECG, cardiac echocardiogram, exercise tolerance test, and stress regional myocardial perfusion study. Her ventricular tachycardia resolved spontaneously. When a sore throat and axillary and cervical adenopathy developed and the rash spread to her limbs, palms, and soles, VDRL (titre 16) and FTA (positive) tests were done. Skin biopsy showed dermal perivascular lymphoplasmacytic infiltrates with endothelial prominence typical of secondary syphilis, but spirochaetes were not identified by Steiner’s stain. She was treated for secondary syphilis with 2-4 MU of intramuscular benzathine penicillin with resolution of her symptoms. Her husband also had a reactive VDRL and FTA.
383
months after infection the widespread lymphatic dissemination of T pallidum is haematogenous marked by a variable presentation including low-grade fevers, malaise, sore throat, headache, adenopathy, and a rash.’ Tissue invasion by the organism is probably responsible for most of these early manifestations although circulating immune complexes may play a part, especially in the nephropathy of secondary syphilis.4.5 Various non-specific pathological fmdings in the myocardium such as lymphocytic and plasma-cell infiltration with secondary myocardial cell injury and obliterative endarteritis leading to fibrosis have been attributed to syphilis, although this has been widely debated.6 Ventricular tachycardia and extrasystoles have been associated with acute myocarditis of other infectious causes.7.8* Early 20th century workers described arrhythmias with secondary syphilis, but this association is not made in contemporary reports.9 Although the precise cause of ventricular arrythmias cannot be established, the temporal relation with secondary syphilis raises the possibility of syphilitic myocarditis. The wide spectrum of illnesses caused by T pallidum coupled with the growing frequency of the disease behoves doctors to have a high index of suspicion.
Several weeks
to
and
PAUL BECHERER DAVID GUTSCH JANET FISCHER
University of North Carolina, Chapel Hill, North Carolina 27599, USA 1 Center for Disease Control
Congenital syphilis: New York City, 1986-1988. MMWR
1989, 38: 825-29. 2 Andrus
JK, Fleming DW, Harger DR, et al. Partner notification: can it control epidemic syphilis? Ann Intern Med 1990; 112: 539-43. Stokes JH Modem clinical syphilology, 2nd ed Philadelphia: W B Saunders, 1934. Gamble CN, Reardan JB Immunopathogenesis of syphilitic glomerulonephritis elution of antitreponemal antibody from glomerular immune complex deposits. N Engl J Med 1975, 292: 449-54 Turner T, Hardy P, Newman B. Infectivity tests in syphilis. Br J Vener Dis 1969, 45:
3 4
5
183-96. 6 Saphir O Syphilitic myocarditis Arch Pathol 1932, 13: 266-95. 7 Vikerfors T, Stjerna A, Olcen P, Malmcrona R, Magnius L Acute myocarditis. Acta
Med Scand 1988; 223: 45-52
Karjalainen J, Viitasals M, Kala R, Heikkila J. 24-hour electrocardiographic recordings in mild acute infectious myocarditis. Ann Clin Res 1984; 16: 34-39. Anders JM. Certain syphilitic affections of the heart and aorta. Am J Med Sci 1915,
8 9
150: 835-42
Co-infection with HTLV-I/II and HIV-1 SIR,-Dr Page and colleagues (June 16,
p
1439)
assert
that
HTLV-I/II seropositivity adversely affects the clinical outcome for HIV-1 seropositive intravenous drug users. However, the method used to measure anti-HTLV-I/ IIcalls into question the validity of their fmdings. By measuring antibodies to p24 antigen only Page et al have not met the criterion for seropositivity that antibodies against bothgag and env gene products be demonstrated.Although an assay based on p24 antigen is likely to detect antibodies against both HTLV-1 and HTLV-11, the sensitivity and specificity of the assay used are not given. False-positive results will be generated by an assay based on gag antigen alone: rates up to 10% have been reported in a range of assays2 and use of p24 based immunoassays has previously been associated with a high degree of non-specificity for HTLV-1 infectionFurthermore, confirmation by an independent method is essential. Even when several screening assays have been used, confirmation is difficult. Western blot assays are not reliable because env encoded glycoproteins are poorly transferred to nitrocellulose, and a radioimmunoprecipitation assay is often needed. Virus Reference Laboratory, Central Public Health Laboratory, London NW9 5HT, UK
JENNIFER H. C. TOSSWILL
Infectious Diseases Unit, Department of Medicine,
Royal Postgraduate
Medical School,
London W12 1 US Public Health Service Working
Group Licensure of screening tests for antibody human T-lymphotropic virus type I MMWR 1988; 37: 736-47 Weber JN, Banatvala N, Clayden S, et al HTLV-I infection in Papua New Guinea. evidence for serologic false positivity J Infect Dis 1989, 159: 1025-28 Koprowski H, DeFreitas EC, Harper ME, et al Multiple sclerosis and human T-cell lymphotropic retroviruses Nature 1985; 318: 154-60 to
2
3
JONATHAN N. WEBER
SIR,-Dr Page and colleagues report that dual infection with affects survival in HIV-1-positive intravenous drug users, supporting findings in homosexual men.’ They suppose that carriage of HTLV-I/II, which suppresses cell-mediated immunity,2 compounds the immunosuppression due to HIV, thereby accelerating disease progression. Although this is a plausible argument recent observations on the biology of these
HTLV-I/II adversely
retroviruses
provide attractive alternatives.
HTLV-I/III code for two trans-acting regulatory proteins tax and rex,3 which are expressed at low levels in carriers of HTLV-I.4 HTLV-1 tax can activate cellular genes which may be involved in the synergistic effect. These include up-regulation of interleukin-2 (IL-2), IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor (GM-CSF); and down-regulation of the expression of human &bgr;-polymerase, a cellular enzyme involved in host cell repair.5 Furthermore, the HTLV-I tax product stimulates the HIV-1 enhancer besides its own enhancerthereby amplifying viral gene expression, which could accelerate disease progression in HIV-1. The tax product may influence T-cell proliferation through induction of both IL-2 and its receptor, activating and accelerating production of HIV-1 virions resulting in T cell death. Upregulation of cytokine GM-CSF by the HTLV-I/II tax product may also accelerate progression by enhancing HIV-1 replication in monocytes.8 The HTLV-IjII rex product is required for viral replication; however, it can functionally replace the HIV-1 rev product and rescue replication of a rev deficient HIV-1 provirus.9 This complementation may further augment disease progression. Department of Haematological Medicine, King’s College School of Medicine and Dentistry, London SE5 9PJ, UK
A. PAGLIUCA G. J. MUFTI
1 Bartholomew C, Blattner W, Cleghorn F. Progression to AIDS in homosexual men co-infected with HIV and HTLV-I in Trinidad. Lancet 1987, ii: 1469 2. Imai J, Hinuma Y. Epstein-Barr virus specific antibodies in patients with adult T-cell leukemia and healthy ATLV-carriers. Int J Cancer 1983; 31: 197-200. 3. Rosenblatt JD, Chen ISY, Wachsman W. Infection with HTLV-I and HTLV-II: evolving concepts Semin Hematol 1988; 25: 230-46. 4. Kinishita T, Shimoyama M, Tobinai K, et al. Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci USA 1989, 86: 5620-24. 5. Jeang KT, Widen SG, Semmes OJ, Wilson SH. HTLV-I trans-activator protein, tax, is a transrepressor of the human &bgr;-polymerase gene Science 1990; 247: 1082-84. 6. Bohnlein E, Siekevitz M, Ballard DW, et al Stimulation of the human immunodeficiency virus type I enhancer by the human T cell leukaemia virus type I tax gene product involves the action of inducible cellular proteins J Virol 1989; 63: 1578-86. 7 Nimer SD, Gasson JC, Hu K, et al. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene 1989; 4: 671-76. 8. Koyanagi Y, O’Bnen WA, Zhao JQ, Golde DW, Gasson JC, Chen ISY. Cytokines alter production of HIV-I from primary mononuclear phagocytes. Science 1988; 241: 1673-75. 9. Rimsky L, Hauber J, Dukovich M, et al. Functional replacement of the HIV-I rev protein by the HTLV-I rex protein. Nature 1988, 335: 738-40.
Unusual
cause
of
pharyngeal ulcerations
in
AIDS SIR,-Dr Gorin and colleagues (June 2, p 1343) report successful thalidomide therapy in hyperalgic pharyngeal ulcerations of AIDS, as described previously.’ We also have experience of such ulcerations. Pneumocystis carinii pneumonia was diagnosed in a 34-year-old homosexual man in 1986. Soon after, he was admitted with co-trimoxazole-induced neutropenia and Escherichia cola septicaemia. In 1987 the patient was treated with zidovudine and pentamidine aerosol. Thereafter, nine episodes of painful pharyngeal ulcerations occurred over 2 years, often with neutropenia not related to zidovudine. The ulcerations were unilateral and led to complete destruction of the right pharyngeal wall. While all microbiological samples remained sterile, treatment with parenteral amphotericin B and broad-spectrum antibiotics was effective. Thalidomide was given as prophylaxis for the ulcerations but they recurred. Although daily fluconazole was given, early in 1989 pulmonary infiltrates and an abscess with cavity due to mucor (Abszdia coryrnbifera was found in both sputum and
