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Sterile pyuria and Chlamydia trachomatis
385
Haemoglobin and reticulocyte
counts in
myeloma patient
on
EPO.
ferrous sulphate 200 mg twice daily because of the reduced iron stores and functional iron deficiency that may occur with EPO.’ The response is shown in the figure. Hb reached 10 g/dl during week 8. The reticulocytosis and rise in Hb in response to EPO and ferrous sulphate subsided when EPO was stopped and recurred on restarting EPO. EPO is now being given on a reducing maintenance dose. The patient noticed a substantial improvement in symptoms and she can now perform several routine tasks that had previously been beyond her. There has been no further deterioration in renal function. A repeat bone-marrow aspirate on June 12 showed a reduction in plasma cells to 18%. Treatment with oral cytotoxic drugs (dexamethasone and melphalan) has continued. Even in the presence of substantial bone-marrow infiltration by tumour a useful response to EPO may be achieved-a finding with implications for the treatment of patients with malignancies affecting the bone marrow. Such patients are admitted for repeated blood transfusions and subcutaneous EPO may be preferable. Another group of patients who may benefit from this treatment would be those with myeloma in whom intensive chemotherapy may not be indicated but whose anaemia is giving rise to significant clinical problems. For such patients symptoms may be relieved with EPO alone. For patients starting chemotherapy for malignancies such as myeloma, in which a substantial component of the anaemia may be due to marrow infiltration, simultaneous chemotherapy and EPO may raise Hb more rapidly. Hertford County Hospital, Hertford SG14 1 LP, UK
H. P. DAVIS
1 Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis Lancet 1986; ii 1175-77.
Sterile pyuria and Chlamydia trachomatis StR,—Patients who, on routine analysis of urine, have significant pyuna (more than 20 leucocytes/ui) but where no bacteria are cultured are often said to have "sterile pyuria". Previous studies have linked this observation to sexually transmitted disease and to Chlarnydia trachomatis in particular.12 Since reporting our preliminary study on C trachomatis in urine3we have tested 550 samples of urine from male (45 samples) and female (505) patients aged 16-39 years with sterile pyuria. C trachomatis was sought by conventional culture, by direct immunofluorescence (DIF) for cellular inclusions, and by ELISA. 20 ml samples were divided into three and centrifuged at 3000 g for 15 min, the supernatants being discarded. One deposit was examined by DIF (’Imagen’, NovoNordisk); another was resuspended in 1 ml tissue culture transport medium and 0 25 ml
was
inoculated into conventional
McCoy tissue cultures, the results being confirmed by immunofluorescence with the monoclonal antibody used in DIF;
and the third deposit was resuspended in 1 ml C tracholllutis ELI SA transport medium and tested according to the manufacturers protocol (’IDErA’ NovoNordisk). All urine remaining was stored at - 20°C for later evaluation of discordant results by repeat ELISA and/or immunofluorescence for elementary bodies (’MicroTrak’, Syva). 60 (10-9/,,) specimens were positive for C trachomatis-42 by all three methods, 12 by D IF and ELISA only, and 6 by ELISA alone. A further 9 ELISA positives and 1 DIF positive were regarded as false positives since they could not be confirmed by alternative means. 24’% (11/45) of all the male patients and 10.7% (12/112) of women attending an antenatal clinic were positive for C trachornatis by one or more methods. Although culture of C trachorrtatis is the "gold standard" for conventional specimens its sensitivity in this study was only 70% (42/60). DIF on centrifuged deposits detected not only all the viable organisms that were cultured but also another 12 that failed to grow in tissue culture but were positive by ELISA. As a rapid method D IF may be more acceptable than ELISA, being cheaper, quicker, and having a sensitivity of 90% (54/60). ELISA was 100% sensitive (60/60) but it may not be the most specific (9 false positives) when used alone. A combination of DIF and ELISA might achieve 100% sensitivity with enhanced specificity. It seems that up to 10% of cases of sterile pyuria are caused by C trachornatis, the urethra being the probable site of infection (although some females may have had concurrent chlamydial cervicitis). This finding should alert the bacteriology laboratory and clinicians to investigate further for chlamydial infection. Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH, UK
R. S. MATTHEWS S. D. BONIGAL R. WISE
J. Chlamydia trachomatis induced urethritis in female partners of men with nongonococcal urethritis Sex Trans Dis 1979, 6: 69-71. Stamm WE, Wagner KF, Amsel R, et al. Causes of the acute urethral syndrome in women. N Engl J Med 1980; 303: 409-15. Matthews RS, Wise R. Non-invasive sampling method for detecting Chlamydia
1. Paavonen
2 3 4.
trachomatis. Lancet 1989, i: 96 Ridgway GL, Oriel JD, Mumtaz G, Mellars B. Comparison of methods for detecting Chlamydia trachomatis. J Clin Pathol 1986; 39: 232
Obstacle to
early diagnosis of herpes simplex encephalitis via CSF
SIR,-Dr Thomas and her colleagues (July 14, p 113) suggest that early "non-invasive" diagnosis of herpes simplex encephalitis (HSE) by means of lumbar cerebrospinal fluid (CSF) is not possible. In the absence of leptomeningeal inflammation, at the pial-glial border, they propose that the only route by which virus could reach the CSF is by infection of the ependymal or choroid plexus cells lining the ventricles, with liberation of virus into the CSF after cell lysis. Although such a hypothesis might explain why virus is rarely, if ever, cultured from lumbar CSF in HSE/ the suggestion that viral antigen or viral DNA are similarly excluded from CSF is untenable. Choroid plexus and ependymal cells are not a firm barrier (ie, with tight junctions) between CSF and brain parenchyma. Thus, viral protein antigens, viral genes, and subgenome viral DNA may well achieve readier penetration. In addition, early inflammatory reactions-which Thomas et al seem to dismiss-may be a common feature of the disease. Despite difficulties with in-vivo localisation of CNS inflammation, radionuclide brain imagingZ and raised CSF/’serum albumin ratios3 in early HSE do indicate that such inflammation occurs. Our experience4 and that of others’6 is that a diagnosis of HSE can be achieved by immunoassay detection of HSV glycoprotein antigens in lumbar CSF at an early stage of infection. However, because the amount of detectable antigen in CSF from patients with this disease is extremely low, enzyme and radioimmunoassays often work near or at their limits of sensitivity, with the consequent difficulties in reliability and reproducibility. The rapid development of a CNS immune response’ further reduces the availability of detectable virus antigen in CSF. Thomas and colleagues’ dismissal of the potential of polymerase chain reaction (PCR) amplification of CSF-bome HSV nucleic acid
Haemoglobin and reticulocyte
counts in
myeloma patient
on
EPO.
ferrous sulphate 200 mg twice daily because of the reduced iron stores and functional iron deficiency that may occur with EPO.’ The response is shown in the figure. Hb reached 10 g/dl during week 8. The reticulocytosis and rise in Hb in response to EPO and ferrous sulphate subsided when EPO was stopped and recurred on restarting EPO. EPO is now being given on a reducing maintenance dose. The patient noticed a substantial improvement in symptoms and she can now perform several routine tasks that had previously been beyond her. There has been no further deterioration in renal function. A repeat bone-marrow aspirate on June 12 showed a reduction in plasma cells to 18%. Treatment with oral cytotoxic drugs (dexamethasone and melphalan) has continued. Even in the presence of substantial bone-marrow infiltration by tumour a useful response to EPO may be achieved-a finding with implications for the treatment of patients with malignancies affecting the bone marrow. Such patients are admitted for repeated blood transfusions and subcutaneous EPO may be preferable. Another group of patients who may benefit from this treatment would be those with myeloma in whom intensive chemotherapy may not be indicated but whose anaemia is giving rise to significant clinical problems. For such patients symptoms may be relieved with EPO alone. For patients starting chemotherapy for malignancies such as myeloma, in which a substantial component of the anaemia may be due to marrow infiltration, simultaneous chemotherapy and EPO may raise Hb more rapidly. Hertford County Hospital, Hertford SG14 1 LP, UK
H. P. DAVIS
1 Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis Lancet 1986; ii 1175-77.
Sterile pyuria and Chlamydia trachomatis StR,—Patients who, on routine analysis of urine, have significant pyuna (more than 20 leucocytes/ui) but where no bacteria are cultured are often said to have "sterile pyuria". Previous studies have linked this observation to sexually transmitted disease and to Chlarnydia trachomatis in particular.12 Since reporting our preliminary study on C trachomatis in urine3we have tested 550 samples of urine from male (45 samples) and female (505) patients aged 16-39 years with sterile pyuria. C trachomatis was sought by conventional culture, by direct immunofluorescence (DIF) for cellular inclusions, and by ELISA. 20 ml samples were divided into three and centrifuged at 3000 g for 15 min, the supernatants being discarded. One deposit was examined by DIF (’Imagen’, NovoNordisk); another was resuspended in 1 ml tissue culture transport medium and 0 25 ml
was
inoculated into conventional
McCoy tissue cultures, the results being confirmed by immunofluorescence with the monoclonal antibody used in DIF;
and the third deposit was resuspended in 1 ml C tracholllutis ELI SA transport medium and tested according to the manufacturers protocol (’IDErA’ NovoNordisk). All urine remaining was stored at - 20°C for later evaluation of discordant results by repeat ELISA and/or immunofluorescence for elementary bodies (’MicroTrak’, Syva). 60 (10-9/,,) specimens were positive for C trachomatis-42 by all three methods, 12 by D IF and ELISA only, and 6 by ELISA alone. A further 9 ELISA positives and 1 DIF positive were regarded as false positives since they could not be confirmed by alternative means. 24’% (11/45) of all the male patients and 10.7% (12/112) of women attending an antenatal clinic were positive for C trachornatis by one or more methods. Although culture of C trachorrtatis is the "gold standard" for conventional specimens its sensitivity in this study was only 70% (42/60). DIF on centrifuged deposits detected not only all the viable organisms that were cultured but also another 12 that failed to grow in tissue culture but were positive by ELISA. As a rapid method D IF may be more acceptable than ELISA, being cheaper, quicker, and having a sensitivity of 90% (54/60). ELISA was 100% sensitive (60/60) but it may not be the most specific (9 false positives) when used alone. A combination of DIF and ELISA might achieve 100% sensitivity with enhanced specificity. It seems that up to 10% of cases of sterile pyuria are caused by C trachornatis, the urethra being the probable site of infection (although some females may have had concurrent chlamydial cervicitis). This finding should alert the bacteriology laboratory and clinicians to investigate further for chlamydial infection. Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH, UK
R. S. MATTHEWS S. D. BONIGAL R. WISE
J. Chlamydia trachomatis induced urethritis in female partners of men with nongonococcal urethritis Sex Trans Dis 1979, 6: 69-71. Stamm WE, Wagner KF, Amsel R, et al. Causes of the acute urethral syndrome in women. N Engl J Med 1980; 303: 409-15. Matthews RS, Wise R. Non-invasive sampling method for detecting Chlamydia
1. Paavonen
2 3 4.
trachomatis. Lancet 1989, i: 96 Ridgway GL, Oriel JD, Mumtaz G, Mellars B. Comparison of methods for detecting Chlamydia trachomatis. J Clin Pathol 1986; 39: 232
Obstacle to
early diagnosis of herpes simplex encephalitis via CSF
SIR,-Dr Thomas and her colleagues (July 14, p 113) suggest that early "non-invasive" diagnosis of herpes simplex encephalitis (HSE) by means of lumbar cerebrospinal fluid (CSF) is not possible. In the absence of leptomeningeal inflammation, at the pial-glial border, they propose that the only route by which virus could reach the CSF is by infection of the ependymal or choroid plexus cells lining the ventricles, with liberation of virus into the CSF after cell lysis. Although such a hypothesis might explain why virus is rarely, if ever, cultured from lumbar CSF in HSE/ the suggestion that viral antigen or viral DNA are similarly excluded from CSF is untenable. Choroid plexus and ependymal cells are not a firm barrier (ie, with tight junctions) between CSF and brain parenchyma. Thus, viral protein antigens, viral genes, and subgenome viral DNA may well achieve readier penetration. In addition, early inflammatory reactions-which Thomas et al seem to dismiss-may be a common feature of the disease. Despite difficulties with in-vivo localisation of CNS inflammation, radionuclide brain imagingZ and raised CSF/’serum albumin ratios3 in early HSE do indicate that such inflammation occurs. Our experience4 and that of others’6 is that a diagnosis of HSE can be achieved by immunoassay detection of HSV glycoprotein antigens in lumbar CSF at an early stage of infection. However, because the amount of detectable antigen in CSF from patients with this disease is extremely low, enzyme and radioimmunoassays often work near or at their limits of sensitivity, with the consequent difficulties in reliability and reproducibility. The rapid development of a CNS immune response’ further reduces the availability of detectable virus antigen in CSF. Thomas and colleagues’ dismissal of the potential of polymerase chain reaction (PCR) amplification of CSF-bome HSV nucleic acid