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Bilateral pleural effusion and a subsegmental infiltrate due to Chlamydia pneumoniae in a mechanically ventilated patient
The Netherlands Journal of Medicine 2001;59:62–65
Brief report
Bilateral pleural effusion and a subsegmental infiltrate due to Chlamydia pneumoniae in a mechanically ventilated patient A.W.F.T. Toorians a , *, J.A. Pneumatikos a , H.L. Zaaijer b , R.J.M Strack van Schijndel a a
b
Intensive Care Adults, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands Department of Medical Microbiology and Infection Control, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands Received 21 December 2000; received in revised form 26 April 2001; accepted 29 May 2001
Abstract A case of Chlamydia pneumoniae infection with bilateral pleural effusion and a subsegmental pulmonary infiltrate in an intubated and mechanically ventilated critically ill patient is described. Diagnosis was made by polymerase chain reaction on both pleural effusions. 2001 Elsevier Science B.V. All rights reserved. Keywords: Chlamydia pneumoniae; Polymerase chain reaction; Pleural effusion; Mechanical ventilation
Introduction Chlamydia ( C.) pneumoniae has been implicated as the causative agent in about 10% of cases of community acquired pneumonia [1,2]. The pneumonia is usually characterized by a mild to moderate interstitial inflammation in otherwise normal adults. However, C. pneumoniae may cause severe pneumonia and acute respiratory failure especially in patients with preexisting serious chronic diseases [2–4]. It also has been reported as a cause of hospital acquired pneumonia, although the exact role of C. pneumoniae in these cases is uncertain, since diagnosis was based on serological tests alone without isolation of the organism [2,5]. Nevertheless, it is now clear that a chronic carrier state of this obligate intracellular *Corresponding author. Tel.: 1 31-20-4442-445; fax: 1 31-204442-392. E-mail address: [email protected] (A.W.F.T. Toorians).
bacterium may occur. Unfortunately, the differentiation of a nosocomial infection from a reactivation of a latent infect of C. pneumoniae is extremely difficult. We describe a case of a late development of bilateral pleural effusion with a subsegmental pulmonary infiltrate due to C. pneumoniae in a critically ill, intubated and mechanically ventilated patient treated in an intensive care unit (ICU) for several weeks after an episode of Gram negative sepsis. The diagnosis was confirmed by rapid detection of C. pneumoniae in the fluid of both pleural effusions by polymerase chain reaction (PCR).
Case report An 80-year-old woman was admitted to the intensive care unit with septic shock due to cholangitis, pancreatitis and empyema of the gallbladder. She
0300-2977 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 01 )00136-X
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection
received regular treatment and ventilatory support to compensate for the septic shock. Sphincterotomy by means of endoscopic retrograde cholangiopancreaticography led to prompt drainage of bile. The empyema of the gall bladder was treated by percutaneous drainage. Klebsiella ( K.) oxytoca and Aeromonas hydrophila, cultured from blood and bile were susceptible to gentamicin and piperacillin, which had already been started. Pancreatic enzymes and cholestatic liver enzymes improved thereafter; however, her septic syndrome had a protracted and complicated course. Recurrence of fever on the 16th day after admission was explained by a central venous catheter infection. After exchange of the central line the body temperature normalized, cultures of blood and the tip of the catheter remained sterile. A new episode of fever developed on the 20th day after admission, currently of intermittent character, with temperature peaks of 398C. A new, thorough search for a focus did not reveal a convincing clue, apart from pleural fluid in the apex of the right hemithorax. K. oxytoca and Candida albicans cultured from sputum were considered to be colonizers in accordance with the Center of Disease Control definition of ventilator associated pneumonia because consolidations were not seen on the chest radiograph [6]. Therefore these microorganisms were not treated with antibiotics. Then, 28 days after admission, she developed a peripheral subsegmental infiltrate in the right upper lobe and bilateral pleural effusions, for which a
63
diagnostic procedure was performed (Fig. 1). Bilateral pleural puncture revealed straw-colored exudate. Gram stain showed 1 1 1 leucocytes. Routine cultures of bilateral pleural fluids remained sterile. Acid fast stain was negative. Since there was a strong likelihood of an infectious cause for this leucocyte-containing pleural exudate, the search for other pulmonary pathogens was continued. Both PCR on pleural fluid and serology specific for Mycoplasma ( M) pneumoniae were negative. PCR on sputum for M. tuberculosis was also negative. However, C. pneumoniae specific IgA and IgG antibodies were positive by immunofluorescence, indicating an active infection. PCR on both pleural fluids for C. pneumoniae confirmed the current infection. PCR was performed as described before [7]. Treatment with doxycyclin was initiated. Temperature normalized in 48 h. The patient could successfully be weaned off mechanical ventilation in 7 days and the bilateral pleural effusion and subsegmental pulmonary infiltrate disappeared. Doxycylin was prescribed for 3 weeks. To further substantiate an active Chlamydia infection follow-up sera were tested, using two additional tests employing two different antigens of C. pneumoniae. A recombinant major outer membrane protein ELISA (MOMP, Savyon Diagnostics, Ashdod, Israel) and a recombinant lipopolysaccharide ELISA (LPS, Medac , Hamburg, Germany) both showed declining IgA titers: sample cut-off ratios of IgA anti-MOMP were on day 28: 2.2, on day 41: 2.1 and on day 52: 1.6. Sample cut-off ratios of IgA anti-LPS were on day 28: 1.4, day 41: 0.8 and on day 52: 0.8. A second PCR for C. pneumoniae on both pleural fluids 10 days after starting with doxycyclin was negative. The clinical condition of the patient improved to a level where she was able to perform basic activities of daily life by herself. Thereafter she was discharged from the hospital.
Discussion
Fig. 1. Peripheral subsegmental infiltrate in the right upper lobe and bilateral pleural effusions.
Ever since the initial reports of C. pneumoniae infection emphasized a rather mild atypical pneumonia, frequently preceded by pharyngitis, the list of clinical manifestations of acute C. pneumoniae infection has expanded. C. pneumoniae may cause
The Netherlands Journal of Medicine 2001;59:62 – 65
64
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection
severe pneumonia and respiratory failure especially in patients with chronic underlying disorders [2]. C. pneumoniae has also been reported as a cause of hospital-acquired pneumonia [3]. However, the exact role of C. pneumoniae in these cases is uncertain since diagnosis was based on serological tests alone without isolation of the organism or identification of other potential etiological agents. It is possible that C. pneumoniae acted as a copathogen, or that infection represented reactivation of quiescent infection in the lungs of very sick patients. C. pneumoniae has been reported to be cultured from bronchoalveolar lavage fluid of patients with human immunodeficiency virus (HIV) infection [4]. This suggests that C. pneumoniae was already present in the lungs of these patients, though it did not necessarily cause their acute respiratory illness. We present the case of an aged, critically ill, intubated and mechanically ventilated patient who developed bilateral pleural effusion and a subsegmental infiltrate due to C. pneumoniae. To our knowledge this is the first reported case of such an unusual infection due to C. pneumoniae, diagnosed by positive PCR in the fluid of both pleural effusions [7]. It cannot be discerned whether this severe pneumonia was a result of nosocomial infection or represented reactivation of a latent infection in this critically ill patient. Nosocomial infections can be established only by means of an extensive study of the environment of the patient, followed by a genetic analysis of Chlamydia isolates. For clinical purposes this approach is not feasible, though a clinician should be aware of the possibilities of a nosocomial infection or a reactivation of a latent infection. In our case, fever with a newly developed peripheral subsegmental infiltrate and leucocytes containing pleural exudates suggested infection. After routine cultures remained sterile, the possible role of less usual pulmonary pathogens was tested, which in our case proved to be C. pneumoniae. Hereafter diagnostic confirmation and relatively simple treatment will be discussed briefly. The laboratory diagnosis of C. pneumoniae infections is difficult. C. pneumoniae isolation by culture is problematic, although it is still considered by many to be the gold standard. The complement fixation test has low sensitivity and specificity [2]. Serologic diagnosis by the microimmunofluores-
cent (MIF) antibody test is hampered by slow antibody response to C. pneumoniae. Furthermore, the value of MIF serology has been questioned since a lack of specific antibodies has been observed in sera of patients in whom the organism could be isolated [5]. Moreover, specific antibiotic treatment may suppress the antibody response [8]. Despite these shortcomings the MIF is regarded as the current method of choice for the laboratory diagnosis of an acute C. pneumoniae infection [9]. It has been reported that IgA antibodies are a reliable immunological markers of primary, chronic and recurrent infections. These antibodies usually decline rapidly to baseline levels following treatment and eradication of the C. pneumoniae infections [10]. The persistence of elevated IgA antibody titers is generally considered as a sign of chronic infection [10]. After a C. pneumoniae specific PCR confirmed this infection in our patient, we performed two additional tests for IgA antibodies against two different antigens of C. pneumoniae, MOMP and LPS. Signals in both assays declined during the course. The decline of IgA anti-LPS was most prominent. New molecular methods such as PCR are more sensitive than cell culture at demonstrating the presence of C. pneumoniae [8,11]. The meaning of isolated detection of chlamydial DNA by PCR is still under debate: possibly the DNA was ingested by macrophages elsewhere in the body. However, in our case serological results corroborated the PCR findings. Tetracyclines or macrolides are considered to be the treatment of choice in C. pneumoniae infection. Because these infections have shown a remarkable tendency to recur, treatment should be continued for 2 or preferably 3 weeks [12]. In conclusion, we suggest that clinicians working in ICUs bear in mind the possibility of C. pneumoniae in respiratory tract infection in intubated and mechanically ventilated patients, where there is a strong suspicion of lung and or pleural infection and where routine cultures do not reveal a causative pathogen.
References [1] Grayston JT. Infections caused by Chlamydia pneumonia, strain TWAR. Clin Infect Dis 1992;15:757–61.
The Netherlands Journal of Medicine 2001;59:62 – 65
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection [2] Marrie TJ, Grayston JT, Wang SP, Kuo CC. Pneumonia associated with TWAR strain of chlamydia. Ann Intern Med 1987;106:507–11. [3] Grayston JT, Diwan VK, Cooney M, Wang SP. Communityand hospital-acquired pneumonia associated with chlamydia TWAR infection demonstrated serologically. Arch Intern Med 1989;149:169–73. [4] Augenbraun MH, Chirgwin K, Roblin PM, Ladman D, Hammerschlag MR. Isolation of Chlamydia pneumonia from the lungs of patients infected with human immunodeficiency virus. J Clin Microbiol 1991;29:401–2. [5] Kuo CC, Jackson LA, Campbell LA, Grayston JT. Chlamydia pneumoniae (TWAR) (Review). Clin Microbiol Rev 1995;8:451–61. [6] Guideline for prevention of nosocomial pneumonia. Centers for Disease Control and Prevention (Review). Respir care 1994;39:1191–236. [7] Tjhie HTJ, Roosendaal R, Walboomers JMM, Theunissen JJH, Tjon Lim Sang RRM, Meijer CJLM et al. Detection of Chlamydia pneumoniae using a general Chlamydia PCR with species differentiation after hybridization. J Microbiol Meth 1993;18:137–50.
65
[8] Gaydos CA, Roblin PM, Hammerschlag MR, Hyman CL, Eiden JJ, Schachter J et al. Diagnostic utility of PCR-enzyme immunoassay, culture and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients. J Clin Microbiol 1994;32:903–5. [9] Peeling RW, Wang SP, Grayston JT, Blasi F, Boman J, Clad A et al. Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results. J Infect Dis 2000;181(Suppl. 3):S426–9. [10] Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen ¨ ¨ PH et al. Serological evidence of an association MS, Makela of a novel chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2:983– 6. [11] Jantos CA, Roggendorf R, Wuppermann FN, Hegemann JH. Rapid detection of Chlamydia pneumonia by PCR-enzyme immunoassay. J Clin Microbiol 1998;36:1890–4. [12] Grayston JT, Kuo CC, Wang SP, Altman J. A new Chlamydia psittaci strain TWAR, isolated in acute respiratory tract infections. New Engl J Med 1986;315:161–8.
The Netherlands Journal of Medicine 2001;59:62 – 65
Brief report
Bilateral pleural effusion and a subsegmental infiltrate due to Chlamydia pneumoniae in a mechanically ventilated patient A.W.F.T. Toorians a , *, J.A. Pneumatikos a , H.L. Zaaijer b , R.J.M Strack van Schijndel a a
b
Intensive Care Adults, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands Department of Medical Microbiology and Infection Control, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands Received 21 December 2000; received in revised form 26 April 2001; accepted 29 May 2001
Abstract A case of Chlamydia pneumoniae infection with bilateral pleural effusion and a subsegmental pulmonary infiltrate in an intubated and mechanically ventilated critically ill patient is described. Diagnosis was made by polymerase chain reaction on both pleural effusions. 2001 Elsevier Science B.V. All rights reserved. Keywords: Chlamydia pneumoniae; Polymerase chain reaction; Pleural effusion; Mechanical ventilation
Introduction Chlamydia ( C.) pneumoniae has been implicated as the causative agent in about 10% of cases of community acquired pneumonia [1,2]. The pneumonia is usually characterized by a mild to moderate interstitial inflammation in otherwise normal adults. However, C. pneumoniae may cause severe pneumonia and acute respiratory failure especially in patients with preexisting serious chronic diseases [2–4]. It also has been reported as a cause of hospital acquired pneumonia, although the exact role of C. pneumoniae in these cases is uncertain, since diagnosis was based on serological tests alone without isolation of the organism [2,5]. Nevertheless, it is now clear that a chronic carrier state of this obligate intracellular *Corresponding author. Tel.: 1 31-20-4442-445; fax: 1 31-204442-392. E-mail address: [email protected] (A.W.F.T. Toorians).
bacterium may occur. Unfortunately, the differentiation of a nosocomial infection from a reactivation of a latent infect of C. pneumoniae is extremely difficult. We describe a case of a late development of bilateral pleural effusion with a subsegmental pulmonary infiltrate due to C. pneumoniae in a critically ill, intubated and mechanically ventilated patient treated in an intensive care unit (ICU) for several weeks after an episode of Gram negative sepsis. The diagnosis was confirmed by rapid detection of C. pneumoniae in the fluid of both pleural effusions by polymerase chain reaction (PCR).
Case report An 80-year-old woman was admitted to the intensive care unit with septic shock due to cholangitis, pancreatitis and empyema of the gallbladder. She
0300-2977 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 01 )00136-X
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection
received regular treatment and ventilatory support to compensate for the septic shock. Sphincterotomy by means of endoscopic retrograde cholangiopancreaticography led to prompt drainage of bile. The empyema of the gall bladder was treated by percutaneous drainage. Klebsiella ( K.) oxytoca and Aeromonas hydrophila, cultured from blood and bile were susceptible to gentamicin and piperacillin, which had already been started. Pancreatic enzymes and cholestatic liver enzymes improved thereafter; however, her septic syndrome had a protracted and complicated course. Recurrence of fever on the 16th day after admission was explained by a central venous catheter infection. After exchange of the central line the body temperature normalized, cultures of blood and the tip of the catheter remained sterile. A new episode of fever developed on the 20th day after admission, currently of intermittent character, with temperature peaks of 398C. A new, thorough search for a focus did not reveal a convincing clue, apart from pleural fluid in the apex of the right hemithorax. K. oxytoca and Candida albicans cultured from sputum were considered to be colonizers in accordance with the Center of Disease Control definition of ventilator associated pneumonia because consolidations were not seen on the chest radiograph [6]. Therefore these microorganisms were not treated with antibiotics. Then, 28 days after admission, she developed a peripheral subsegmental infiltrate in the right upper lobe and bilateral pleural effusions, for which a
63
diagnostic procedure was performed (Fig. 1). Bilateral pleural puncture revealed straw-colored exudate. Gram stain showed 1 1 1 leucocytes. Routine cultures of bilateral pleural fluids remained sterile. Acid fast stain was negative. Since there was a strong likelihood of an infectious cause for this leucocyte-containing pleural exudate, the search for other pulmonary pathogens was continued. Both PCR on pleural fluid and serology specific for Mycoplasma ( M) pneumoniae were negative. PCR on sputum for M. tuberculosis was also negative. However, C. pneumoniae specific IgA and IgG antibodies were positive by immunofluorescence, indicating an active infection. PCR on both pleural fluids for C. pneumoniae confirmed the current infection. PCR was performed as described before [7]. Treatment with doxycyclin was initiated. Temperature normalized in 48 h. The patient could successfully be weaned off mechanical ventilation in 7 days and the bilateral pleural effusion and subsegmental pulmonary infiltrate disappeared. Doxycylin was prescribed for 3 weeks. To further substantiate an active Chlamydia infection follow-up sera were tested, using two additional tests employing two different antigens of C. pneumoniae. A recombinant major outer membrane protein ELISA (MOMP, Savyon Diagnostics, Ashdod, Israel) and a recombinant lipopolysaccharide ELISA (LPS, Medac , Hamburg, Germany) both showed declining IgA titers: sample cut-off ratios of IgA anti-MOMP were on day 28: 2.2, on day 41: 2.1 and on day 52: 1.6. Sample cut-off ratios of IgA anti-LPS were on day 28: 1.4, day 41: 0.8 and on day 52: 0.8. A second PCR for C. pneumoniae on both pleural fluids 10 days after starting with doxycyclin was negative. The clinical condition of the patient improved to a level where she was able to perform basic activities of daily life by herself. Thereafter she was discharged from the hospital.
Discussion
Fig. 1. Peripheral subsegmental infiltrate in the right upper lobe and bilateral pleural effusions.
Ever since the initial reports of C. pneumoniae infection emphasized a rather mild atypical pneumonia, frequently preceded by pharyngitis, the list of clinical manifestations of acute C. pneumoniae infection has expanded. C. pneumoniae may cause
The Netherlands Journal of Medicine 2001;59:62 – 65
64
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection
severe pneumonia and respiratory failure especially in patients with chronic underlying disorders [2]. C. pneumoniae has also been reported as a cause of hospital-acquired pneumonia [3]. However, the exact role of C. pneumoniae in these cases is uncertain since diagnosis was based on serological tests alone without isolation of the organism or identification of other potential etiological agents. It is possible that C. pneumoniae acted as a copathogen, or that infection represented reactivation of quiescent infection in the lungs of very sick patients. C. pneumoniae has been reported to be cultured from bronchoalveolar lavage fluid of patients with human immunodeficiency virus (HIV) infection [4]. This suggests that C. pneumoniae was already present in the lungs of these patients, though it did not necessarily cause their acute respiratory illness. We present the case of an aged, critically ill, intubated and mechanically ventilated patient who developed bilateral pleural effusion and a subsegmental infiltrate due to C. pneumoniae. To our knowledge this is the first reported case of such an unusual infection due to C. pneumoniae, diagnosed by positive PCR in the fluid of both pleural effusions [7]. It cannot be discerned whether this severe pneumonia was a result of nosocomial infection or represented reactivation of a latent infection in this critically ill patient. Nosocomial infections can be established only by means of an extensive study of the environment of the patient, followed by a genetic analysis of Chlamydia isolates. For clinical purposes this approach is not feasible, though a clinician should be aware of the possibilities of a nosocomial infection or a reactivation of a latent infection. In our case, fever with a newly developed peripheral subsegmental infiltrate and leucocytes containing pleural exudates suggested infection. After routine cultures remained sterile, the possible role of less usual pulmonary pathogens was tested, which in our case proved to be C. pneumoniae. Hereafter diagnostic confirmation and relatively simple treatment will be discussed briefly. The laboratory diagnosis of C. pneumoniae infections is difficult. C. pneumoniae isolation by culture is problematic, although it is still considered by many to be the gold standard. The complement fixation test has low sensitivity and specificity [2]. Serologic diagnosis by the microimmunofluores-
cent (MIF) antibody test is hampered by slow antibody response to C. pneumoniae. Furthermore, the value of MIF serology has been questioned since a lack of specific antibodies has been observed in sera of patients in whom the organism could be isolated [5]. Moreover, specific antibiotic treatment may suppress the antibody response [8]. Despite these shortcomings the MIF is regarded as the current method of choice for the laboratory diagnosis of an acute C. pneumoniae infection [9]. It has been reported that IgA antibodies are a reliable immunological markers of primary, chronic and recurrent infections. These antibodies usually decline rapidly to baseline levels following treatment and eradication of the C. pneumoniae infections [10]. The persistence of elevated IgA antibody titers is generally considered as a sign of chronic infection [10]. After a C. pneumoniae specific PCR confirmed this infection in our patient, we performed two additional tests for IgA antibodies against two different antigens of C. pneumoniae, MOMP and LPS. Signals in both assays declined during the course. The decline of IgA anti-LPS was most prominent. New molecular methods such as PCR are more sensitive than cell culture at demonstrating the presence of C. pneumoniae [8,11]. The meaning of isolated detection of chlamydial DNA by PCR is still under debate: possibly the DNA was ingested by macrophages elsewhere in the body. However, in our case serological results corroborated the PCR findings. Tetracyclines or macrolides are considered to be the treatment of choice in C. pneumoniae infection. Because these infections have shown a remarkable tendency to recur, treatment should be continued for 2 or preferably 3 weeks [12]. In conclusion, we suggest that clinicians working in ICUs bear in mind the possibility of C. pneumoniae in respiratory tract infection in intubated and mechanically ventilated patients, where there is a strong suspicion of lung and or pleural infection and where routine cultures do not reveal a causative pathogen.
References [1] Grayston JT. Infections caused by Chlamydia pneumonia, strain TWAR. Clin Infect Dis 1992;15:757–61.
The Netherlands Journal of Medicine 2001;59:62 – 65
A.W.F.T. Toorians et al. / Nosocomial Chlamydia pneumoniae infection [2] Marrie TJ, Grayston JT, Wang SP, Kuo CC. Pneumonia associated with TWAR strain of chlamydia. Ann Intern Med 1987;106:507–11. [3] Grayston JT, Diwan VK, Cooney M, Wang SP. Communityand hospital-acquired pneumonia associated with chlamydia TWAR infection demonstrated serologically. Arch Intern Med 1989;149:169–73. [4] Augenbraun MH, Chirgwin K, Roblin PM, Ladman D, Hammerschlag MR. Isolation of Chlamydia pneumonia from the lungs of patients infected with human immunodeficiency virus. J Clin Microbiol 1991;29:401–2. [5] Kuo CC, Jackson LA, Campbell LA, Grayston JT. Chlamydia pneumoniae (TWAR) (Review). Clin Microbiol Rev 1995;8:451–61. [6] Guideline for prevention of nosocomial pneumonia. Centers for Disease Control and Prevention (Review). Respir care 1994;39:1191–236. [7] Tjhie HTJ, Roosendaal R, Walboomers JMM, Theunissen JJH, Tjon Lim Sang RRM, Meijer CJLM et al. Detection of Chlamydia pneumoniae using a general Chlamydia PCR with species differentiation after hybridization. J Microbiol Meth 1993;18:137–50.
65
[8] Gaydos CA, Roblin PM, Hammerschlag MR, Hyman CL, Eiden JJ, Schachter J et al. Diagnostic utility of PCR-enzyme immunoassay, culture and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients. J Clin Microbiol 1994;32:903–5. [9] Peeling RW, Wang SP, Grayston JT, Blasi F, Boman J, Clad A et al. Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results. J Infect Dis 2000;181(Suppl. 3):S426–9. [10] Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen ¨ ¨ PH et al. Serological evidence of an association MS, Makela of a novel chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2:983– 6. [11] Jantos CA, Roggendorf R, Wuppermann FN, Hegemann JH. Rapid detection of Chlamydia pneumonia by PCR-enzyme immunoassay. J Clin Microbiol 1998;36:1890–4. [12] Grayston JT, Kuo CC, Wang SP, Altman J. A new Chlamydia psittaci strain TWAR, isolated in acute respiratory tract infections. New Engl J Med 1986;315:161–8.
The Netherlands Journal of Medicine 2001;59:62 – 65