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A parasitologically proven case of Toxoplasma pneumonia in an immunocompetent pregnant woman
Journal of Infection (I993) z6, 79--8I
CASE REPORT A p a r a s i t o l o g i c a l l y p r o v e n c a s e o f Toxoplasma p n e u m o n i a an immunocompetent pregnant woman
in
E. Candolfi,* F. de Blay,T D. Rey,~ D. C h r i s t m a n n , ~ A. Treisser,~ G. P a u l i t a n d T. Kien*
* Institut de Parasitologie et de Mddecine Tropicale, Facultd de Mddecine, F 6700o Strasbourg, t Service de Pneumologie et d'Allergologie, Pavillon Laennec, Hdpitaux Universitaires, F 67000 Strasbourg, ~ Service de Mddecine et de Maladies Infectieuses, Mddicale A, H@itaux Universitaires and Service de Gyndcologie et d'Obstdtrique, M A TESF, Hdpitaux Universitaires, F 67000 Strasbourg, France Accepted for publication 25 March I992 Summary We report a case of primary pulmonary toxoplasmosis in an immunocompetent pregnant woman. Seroconversion did not occur until 2 weeks after detection of the parasite in bronchoalveolar lavage fluid. It is suggested that toxoplasma infection should be considered in any atypical pneumonia in which the X-ray shows diffuse pulmonary infiltrates.
Introduction In the immunocompetent individual, primary infection by Toxoplasma gondii is usually asymptomatic or associated with mild clinical manifestations such as moderate fever and lymphadenopathy. However, visceral localisations have occasionally been reported in patients who have no evidence of an underlying immunodeficiency.1 We report a case of pulmonary toxoplasmosis in an immunocompetent pregnant woman who had negative serological tests for T. gondii at the time of diagnosis.
Case report A 33-year-old pregnant woman from Cambodia was admitted to the obstetrical department with diffuse abdominal pain and a threat of premature labour. She was 34 weeks pregnant and had a history of nicotine and heroin addiction. She gave a 7 days' history of cough, dyspnoea and fever (38°C). T h e r e were bilateral rales on auscultation and a chest X-ray showed reticulonodular opacities in both lower zones (Plate I). No lymphadenopathy or hepatosplenomegaly was found. Investigations showed a WBC count of I3"3 x io9/1 with lymphopenia ( 6 " 1 5 % ) and CD4 and CD8 T-cell counts of 0"25 and o'oSzxzo9/1 respectively. T h e haemoglobin was 8"6 g/dl, the beta-2-microglobulin 2"9 #g/1 and the neopterin 6"5 g/1. An opportunistic infection was suspected because of her past history of drug addiction, and bronchoalveolar lavage (BAL) was oi63-4453/93/oioo79+o3 $08.00/0
© I993 The British Society for the Study of Infection
80
E. C A N D O L F I E T A L .
performed. An aliquot of B A L fluid was smeared on a microscope slide and stained with Giemsa and G o m o r y - G r o c o t t stains. A further aliquot was inoculated onto M R C 5 tissue cultures as previously described) No pathogens were demonstrated by the direct examination, but tissue cultures showed the presence of Toxoplasma (revealed by immunoperoxidase staining with a rabbit polyclonal antibody). Tests at this time were negative for specific H I V - I and -2 antibodies and antigens on two occasions. In addition, specific I g G and I g M antibodies against Toxoplasma were, surprisingly, undetectable by indirect immunofluorescent ( I F A T ) and enzyme (EIA) immunoassays. T w o weeks after the onset of the p u l m o n a r y disease the serology was still negative. Seroconversion occurred 2 weeks later with the development of low titres of I g G (IO I U / m l ) and I g M (positive I F A T at a dilution of I in 20). Seroconversion was confirmed 2 weeks later for I g G and I g M by E I A and a direct agglutination assay; antibody titres remained low. T w o m o n t h s later, the I g G titre was Io I U / m l and after a further 2 m o n t h s the I g M was still near the cut-off value in the E I A and I F A T . T h e patient was initially treated with a Io-day course of spiramycin (before the results of B A L were known), and the symptoms resolved within I week. W h e n Toxoplasma was identified, the treatment was changed to a combination of pyrimethamine and sulphadiazine for 5 weeks (until delivery). T h e neonate had no signs of congenital toxoplasmosis. I g M antibodies were not detected in the cord blood and mouse inoculation of placental material, cord blood, and amniotic fluid was also negative. At this time, the mother's total and C D 4 lymphocyte counts had returned to normal values. Discussion
It is now clear that pulmonary toxoplasmosis is c o m m o n in i m m u n o compromised patients, usually because of reactivation of a previously acquired infection) In the i m m u n o c o m p e t e n t host, an association between p u l m o n a r y symptoms and primary acquired toxoplasmosis has been suspected by several authors but definitive evidence of Toxoplasma infection was rarely obtained pre-mortem. 1'4 In the present case, primary infection was d o c u m e n t e d by seroconversion 2 weeks after the parasite had been detected in the B A L fluid. T h e specific antibody response was unusual since I g G and I g M antibody titres remained low; presumably this was because of the early initiation of therapy. Our patient had no clinical or biological evidence of an underlying immunosuppression. Despite her past history of heroin addiction, the H I V (HIV-~ and -2, P24 antigenaemia) and H T L V I serology was negative 3 m o n t h s after the diagnosis of pulmonary toxoplasmosis. T h e decrease in the CD4 cell count to 0"25 x io9/1, observed at the time of the clinical onset, may have been related to the toxoplasmosis, as has been observed in other cases of recently acquired Toxoplasma infection) -7 Opportunistic toxoplasmosis with severe clinical manifestations is generally associated with a CD4 cell count below o'I5 x io9/1, s T h e C D 4 count in our patient returned to normal 5 weeks after the onset of pneumonia. This observation strongly supports the hypothesis that the lung may be involved in the early phase of Toxoplasma infection, as is the case in animal
]ournal of Infection
Plate I
Plate I. Chest X-ray showing bilateral reticulonodular opacities in the lower zones in a case of pulmonary toxoplasmosis.
E. CANDOLFI ET AL.
(Facing p. 8o)
T o x o p l a s m a p n e u m o n i a in pregnancy
81
m o d e l s . 9 W i t h r e g a r d to t h e p r a c t i c a l i m p l i c a t i o n s , Toxoplasma s h o u l d be s o u g h t w h e n e v e r a p a t i e n t p r e s e n t s w i t h a t y p i c a l p n e u m o n i a a n d diffuse bilateral infiltrates, 1°, 11 e v e n if h e o r she is i m m u n o c o m p e t e n t . I n a d d i t i o n , t r e a t m e n t w i t h b r o a d - s p e c t r u m a n t i b i o t i c s s h o u l d b e s t a r t e d i m m e d i a t e l y to c o v e r t h e p o s s i b i l i t y o f Toxoplasma i n f e c t i o n , e s p e c i a l l y if t h e p a t i e n t is a pregnant woman. (We thank Professor F. Derouin and Professor J. M. L a n g for their helpful advice and suggestions.)
References I. MacCabe RE, Brooks RG, Dorfman RF, Remington JS. Clinical spectrum in IO7 cases of toxoplasmic lymphadenopathy. Rev Infect Dis I987; 9: 754-774. z. Derouin F, Mazeron MC, Garin Y. Comparative study of tissue culture and mouse inoculation methods for demonstration of Toxoplasma gondii. J Clin Microbiol I987; zS: I597-I6OO. 3. Catteral JR, Hofttin JM, Remington JS. Pulmonary toxoplasmosis. Am Rev Resp Dis I986; 133 : 704-705. 4- Shimoni Z, Raz R, Reichmann N, Flatau E. Pulmonary infiltrate in acute toxoplasmosis. Isr J Med Sci 1989; 25:46-47 • 5. Lin DS, Bowman DD. Cellular responses of cats with primary toxoplasmosis. J Parasitol r99I; 77: 272-279. 6. Luft BJ, Kansas G, Engleman EG, Remington JS. Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis. J lnfect Dis 1984; 15o : 761-767. 7. Sklenar I, Jones TC, Alkan S, Erb P. Association of symptomatic human infection with Toxoplasma gondii with imbalance of monocytes and antigen-specific T cell subsets. J Infect Dis I986; 153:315-324 . 8. Eliaszewicz M, Lecomte I, De Sa M, and East Parisian CISIH group. Relation between decreasing seric CD4 lymphocyte cell count and outcome of toxoplasmosis in AIDS patients : a basis for primary prophylaxis. Abstract Th B 48 x Sixth International Congress on AIDS, San Francisco, USA, June ~99o. 9. Derouin F, Garin Y. Blood and tissue kinetics during acute and chronic infections in mice. Exp Parasitol I99I ; 73: 460-468. IO. Maguire GP, Tatz J, Giosa R, Tauseef A. Diagnosis of pulmonary toxoplasmosis by bronchoalveolar lavage. N Y State J Med I986; 86: 2o4--2o5. I I. Jacobs F, Depierreux M, Goldmann M. et al. Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis. Rev Infect Dis I99I ; 13: 637-64I.
CASE REPORT A p a r a s i t o l o g i c a l l y p r o v e n c a s e o f Toxoplasma p n e u m o n i a an immunocompetent pregnant woman
in
E. Candolfi,* F. de Blay,T D. Rey,~ D. C h r i s t m a n n , ~ A. Treisser,~ G. P a u l i t a n d T. Kien*
* Institut de Parasitologie et de Mddecine Tropicale, Facultd de Mddecine, F 6700o Strasbourg, t Service de Pneumologie et d'Allergologie, Pavillon Laennec, Hdpitaux Universitaires, F 67000 Strasbourg, ~ Service de Mddecine et de Maladies Infectieuses, Mddicale A, H@itaux Universitaires and Service de Gyndcologie et d'Obstdtrique, M A TESF, Hdpitaux Universitaires, F 67000 Strasbourg, France Accepted for publication 25 March I992 Summary We report a case of primary pulmonary toxoplasmosis in an immunocompetent pregnant woman. Seroconversion did not occur until 2 weeks after detection of the parasite in bronchoalveolar lavage fluid. It is suggested that toxoplasma infection should be considered in any atypical pneumonia in which the X-ray shows diffuse pulmonary infiltrates.
Introduction In the immunocompetent individual, primary infection by Toxoplasma gondii is usually asymptomatic or associated with mild clinical manifestations such as moderate fever and lymphadenopathy. However, visceral localisations have occasionally been reported in patients who have no evidence of an underlying immunodeficiency.1 We report a case of pulmonary toxoplasmosis in an immunocompetent pregnant woman who had negative serological tests for T. gondii at the time of diagnosis.
Case report A 33-year-old pregnant woman from Cambodia was admitted to the obstetrical department with diffuse abdominal pain and a threat of premature labour. She was 34 weeks pregnant and had a history of nicotine and heroin addiction. She gave a 7 days' history of cough, dyspnoea and fever (38°C). T h e r e were bilateral rales on auscultation and a chest X-ray showed reticulonodular opacities in both lower zones (Plate I). No lymphadenopathy or hepatosplenomegaly was found. Investigations showed a WBC count of I3"3 x io9/1 with lymphopenia ( 6 " 1 5 % ) and CD4 and CD8 T-cell counts of 0"25 and o'oSzxzo9/1 respectively. T h e haemoglobin was 8"6 g/dl, the beta-2-microglobulin 2"9 #g/1 and the neopterin 6"5 g/1. An opportunistic infection was suspected because of her past history of drug addiction, and bronchoalveolar lavage (BAL) was oi63-4453/93/oioo79+o3 $08.00/0
© I993 The British Society for the Study of Infection
80
E. C A N D O L F I E T A L .
performed. An aliquot of B A L fluid was smeared on a microscope slide and stained with Giemsa and G o m o r y - G r o c o t t stains. A further aliquot was inoculated onto M R C 5 tissue cultures as previously described) No pathogens were demonstrated by the direct examination, but tissue cultures showed the presence of Toxoplasma (revealed by immunoperoxidase staining with a rabbit polyclonal antibody). Tests at this time were negative for specific H I V - I and -2 antibodies and antigens on two occasions. In addition, specific I g G and I g M antibodies against Toxoplasma were, surprisingly, undetectable by indirect immunofluorescent ( I F A T ) and enzyme (EIA) immunoassays. T w o weeks after the onset of the p u l m o n a r y disease the serology was still negative. Seroconversion occurred 2 weeks later with the development of low titres of I g G (IO I U / m l ) and I g M (positive I F A T at a dilution of I in 20). Seroconversion was confirmed 2 weeks later for I g G and I g M by E I A and a direct agglutination assay; antibody titres remained low. T w o m o n t h s later, the I g G titre was Io I U / m l and after a further 2 m o n t h s the I g M was still near the cut-off value in the E I A and I F A T . T h e patient was initially treated with a Io-day course of spiramycin (before the results of B A L were known), and the symptoms resolved within I week. W h e n Toxoplasma was identified, the treatment was changed to a combination of pyrimethamine and sulphadiazine for 5 weeks (until delivery). T h e neonate had no signs of congenital toxoplasmosis. I g M antibodies were not detected in the cord blood and mouse inoculation of placental material, cord blood, and amniotic fluid was also negative. At this time, the mother's total and C D 4 lymphocyte counts had returned to normal values. Discussion
It is now clear that pulmonary toxoplasmosis is c o m m o n in i m m u n o compromised patients, usually because of reactivation of a previously acquired infection) In the i m m u n o c o m p e t e n t host, an association between p u l m o n a r y symptoms and primary acquired toxoplasmosis has been suspected by several authors but definitive evidence of Toxoplasma infection was rarely obtained pre-mortem. 1'4 In the present case, primary infection was d o c u m e n t e d by seroconversion 2 weeks after the parasite had been detected in the B A L fluid. T h e specific antibody response was unusual since I g G and I g M antibody titres remained low; presumably this was because of the early initiation of therapy. Our patient had no clinical or biological evidence of an underlying immunosuppression. Despite her past history of heroin addiction, the H I V (HIV-~ and -2, P24 antigenaemia) and H T L V I serology was negative 3 m o n t h s after the diagnosis of pulmonary toxoplasmosis. T h e decrease in the CD4 cell count to 0"25 x io9/1, observed at the time of the clinical onset, may have been related to the toxoplasmosis, as has been observed in other cases of recently acquired Toxoplasma infection) -7 Opportunistic toxoplasmosis with severe clinical manifestations is generally associated with a CD4 cell count below o'I5 x io9/1, s T h e C D 4 count in our patient returned to normal 5 weeks after the onset of pneumonia. This observation strongly supports the hypothesis that the lung may be involved in the early phase of Toxoplasma infection, as is the case in animal
]ournal of Infection
Plate I
Plate I. Chest X-ray showing bilateral reticulonodular opacities in the lower zones in a case of pulmonary toxoplasmosis.
E. CANDOLFI ET AL.
(Facing p. 8o)
T o x o p l a s m a p n e u m o n i a in pregnancy
81
m o d e l s . 9 W i t h r e g a r d to t h e p r a c t i c a l i m p l i c a t i o n s , Toxoplasma s h o u l d be s o u g h t w h e n e v e r a p a t i e n t p r e s e n t s w i t h a t y p i c a l p n e u m o n i a a n d diffuse bilateral infiltrates, 1°, 11 e v e n if h e o r she is i m m u n o c o m p e t e n t . I n a d d i t i o n , t r e a t m e n t w i t h b r o a d - s p e c t r u m a n t i b i o t i c s s h o u l d b e s t a r t e d i m m e d i a t e l y to c o v e r t h e p o s s i b i l i t y o f Toxoplasma i n f e c t i o n , e s p e c i a l l y if t h e p a t i e n t is a pregnant woman. (We thank Professor F. Derouin and Professor J. M. L a n g for their helpful advice and suggestions.)
References I. MacCabe RE, Brooks RG, Dorfman RF, Remington JS. Clinical spectrum in IO7 cases of toxoplasmic lymphadenopathy. Rev Infect Dis I987; 9: 754-774. z. Derouin F, Mazeron MC, Garin Y. Comparative study of tissue culture and mouse inoculation methods for demonstration of Toxoplasma gondii. J Clin Microbiol I987; zS: I597-I6OO. 3. Catteral JR, Hofttin JM, Remington JS. Pulmonary toxoplasmosis. Am Rev Resp Dis I986; 133 : 704-705. 4- Shimoni Z, Raz R, Reichmann N, Flatau E. Pulmonary infiltrate in acute toxoplasmosis. Isr J Med Sci 1989; 25:46-47 • 5. Lin DS, Bowman DD. Cellular responses of cats with primary toxoplasmosis. J Parasitol r99I; 77: 272-279. 6. Luft BJ, Kansas G, Engleman EG, Remington JS. Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis. J lnfect Dis 1984; 15o : 761-767. 7. Sklenar I, Jones TC, Alkan S, Erb P. Association of symptomatic human infection with Toxoplasma gondii with imbalance of monocytes and antigen-specific T cell subsets. J Infect Dis I986; 153:315-324 . 8. Eliaszewicz M, Lecomte I, De Sa M, and East Parisian CISIH group. Relation between decreasing seric CD4 lymphocyte cell count and outcome of toxoplasmosis in AIDS patients : a basis for primary prophylaxis. Abstract Th B 48 x Sixth International Congress on AIDS, San Francisco, USA, June ~99o. 9. Derouin F, Garin Y. Blood and tissue kinetics during acute and chronic infections in mice. Exp Parasitol I99I ; 73: 460-468. IO. Maguire GP, Tatz J, Giosa R, Tauseef A. Diagnosis of pulmonary toxoplasmosis by bronchoalveolar lavage. N Y State J Med I986; 86: 2o4--2o5. I I. Jacobs F, Depierreux M, Goldmann M. et al. Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis. Rev Infect Dis I99I ; 13: 637-64I.