Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Nov 1;176(5):1327–1333. doi: 10.1084/jem.176.5.1327

Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia

PMCID: PMC2119432  PMID: 1402679

Abstract

Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chusid M. J., Heyrman K. A. An outbreak of Pneumocystis carinii pneumonia at a pediatric hospital. Pediatrics. 1978 Dec;62(6):1031–1035. [PubMed] [Google Scholar]
  2. Edman J. C., Edman U., Cao M., Lundgren B., Kovacs J. A., Santi D. V. Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8625–8629. doi: 10.1073/pnas.86.22.8625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Frenkel J. K., Good J. T., Shultz J. A. Latent Pneumocystis infection of rats, relapse, and chemotherapy. Lab Invest. 1966 Oct;15(10):1559–1577. [PubMed] [Google Scholar]
  4. Lundgren B., Cotton R., Lundgren J. D., Edman J. C., Kovacs J. A. Identification of Pneumocystis carinii chromosomes and mapping of five genes. Infect Immun. 1990 Jun;58(6):1705–1710. doi: 10.1128/iai.58.6.1705-1710.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Masur H., Lane H. C., Kovacs J. A., Allegra C. J., Edman J. C. NIH conference. Pneumocystis pneumonia: from bench to clinic. Ann Intern Med. 1989 Nov 15;111(10):813–826. doi: 10.7326/0003-4819-111-10-813. [DOI] [PubMed] [Google Scholar]
  6. Millard P. R., Heryet A. R. Observations favouring Pneumocystis carinii pneumonia as a primary infection: a monoclonal antibody study on paraffin sections. J Pathol. 1988 Apr;154(4):365–370. doi: 10.1002/path.1711540413. [DOI] [PubMed] [Google Scholar]
  7. Peglow S. L., Smulian A. G., Linke M. J., Pogue C. L., Nurre S., Crisler J., Phair J., Gold J. W., Armstrong D., Walzer P. D. Serologic responses to Pneumocystis carinii antigens in health and disease. J Infect Dis. 1990 Feb;161(2):296–306. doi: 10.1093/infdis/161.2.296. [DOI] [PubMed] [Google Scholar]
  8. Peters S. E., Wakefield A. E., Sinclair K., Millard P. R., Hopkin J. M. A search for Pneumocystis carinii in post-mortem lungs by DNA amplification. J Pathol. 1992 Feb;166(2):195–198. doi: 10.1002/path.1711660217. [DOI] [PubMed] [Google Scholar]
  9. Radio S. J., Hansen S., Goldsmith J., Linder J. Immunohistochemistry of Pneumocystis carinii infection. Mod Pathol. 1990 Jul;3(4):462–469. [PubMed] [Google Scholar]
  10. SHELDON W. H. Subclinical pneumocystis pneumonitis. AMA J Dis Child. 1959 Mar;97(3):287–297. doi: 10.1001/archpedi.1959.02070010289005. [DOI] [PubMed] [Google Scholar]
  11. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  12. Selik R. M., Starcher E. T., Curran J. W. Opportunistic diseases reported in AIDS patients: frequencies, associations, and trends. AIDS. 1987 Sep;1(3):175–182. [PubMed] [Google Scholar]
  13. Singer C., Armstrong D., Rosen P. P., Schottenfeld D. Pneumocystis carinii pneumonia: a cluster of eleven cases. Ann Intern Med. 1975 Jun;82(6):772–777. doi: 10.7326/0003-4819-82-6-722. [DOI] [PubMed] [Google Scholar]
  14. Telzak E. E., Cote R. J., Gold J. W., Campbell S. W., Armstrong D. Extrapulmonary Pneumocystis carinii infections. Rev Infect Dis. 1990 May-Jun;12(3):380–386. doi: 10.1093/clinids/12.3.380. [DOI] [PubMed] [Google Scholar]
  15. Wakefield A. E., Guiver L., Miller R. F., Hopkin J. M. DNA amplification on induced sputum samples for diagnosis of Pneumocystis carinii pneumonia. Lancet. 1991 Jun 8;337(8754):1378–1379. doi: 10.1016/0140-6736(91)93062-e. [DOI] [PubMed] [Google Scholar]
  16. Walzer P. D., Powell R. D., Jr, Yoneda K., Rutledge M. E., Milder J. E. Growth characteristics and pathogenesis of experimental Pneumocystis carinii pneumonia. Infect Immun. 1980 Mar;27(3):928–937. doi: 10.1128/iai.27.3.928-937.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES