Hello my name is Jason Tuter.  I am a graduate student at Western Illinois University.  I am researching plant and fungal interactions between corn and the fungal endophyte, Phialocephala fortiniii.  Using microarrays, genomic analysis can be performed to understand the relationship between the fungus and its host at the molecular level.  This blog is related to medical mycology and is intended to provide information to the general public about medically important fungi.   I hope you enjoy my blog.

Pneumocystis jiroveci: Description and Case Studies

 

 

 

 

Taxonomic Classification

Eukaryota, Fungi, Ascomycota, Archiascomycetes, Pneumocystidales, Pneumocystidaceae, Pneumocystis jiroveci (www.doctorfungus.org, 2013).

General Description and History

Pneumocystis is a fungus in the phylum Ascomycota; in the family Pneumocystidaceae.  Pneumocystis causes an infection with symptoms similar to pneumonia.  The symptoms include cough, fever, dyspnea, and pleural effusion or fluid in the lungs.  It is an obligate parasite only found in primates and rats. This fungus was first described by Carlos Chagas in 1909.  Chagas described it as an evolutionary phase within the life cycle of the protozoa, Trypanosoma cruzi (Stringer et. al., 2002, and Tabarsi, et. al., 2008).    In 1914, it was renamed Pneumocystis carinii after Antonio Carini who provided the samples for  the study (Cushion, 2010), but the fungus was still considered a protozoan until the 1980s.   rRNA sequencing revealed that Pneumocystis is a yeast fungus (www. doctorfungus.org, 2013).   The fungus was then named Pneumocystis jiroveci to describe the species specific to humans.  Pneumocystis carinii is the species found in rats (Aliouat-Denis et. al., 2008).  Macroscopic features cannot be described for this fungus due to the inability to culture this organism outside of its host.  The only microstructures described are in ultrastructure and histochemical analysis of host lung tissue.  It actually lacks ergosterol in its cell membrane.  This makes it resistant to ergosterol biosynthesis inhibitors (Morris & Norris, 2012).    The current techniques used to identify Pneumocystis are phylogenetic analysis and antigen specificity analysis. 

Geographic Distribution

 P. jiroveci have a ubiquitous, worldwide distribution (www.cdc.gov, 2013).  The distribution can be summarized by anywhere an immunocompromised population of humans reside (Thomas & Limper, 2007).  Currently 18 different strains of Pneumocystis jiroveci have been described and are suggested to have coevolved specificially with 33 primate species (Demanche et. al, 2001). 

Habitat and Life Cycle

This fungus is only found in-vivo in infected patients.  Both sexual and asexual forms are found in lung tissue of its host.  The asexual morphotype is the yeast form.  These show as a broken glass appearance on an x-ray (Tabarsi et. al, 2008).  It is an obligate parasite.  Genome analysis determined the lack of protein metabolism pathway genes.  The fungus uses its host’s enzymes and amino acids to create the proteins it needs for its metabolism pathways (Hauser et. al, 2010). The sexual morphotype forms a cyst structure that is easily recognizable.  As the cyst matures and ruptures, releasing the mature spores .

 

Fig 1: The life cycle of Pneumocystis has both sexual and asexual cycles occurring within its host at the same time.  The sexual form is the more pronounced form under microscopy and its main identifying characteristic for diagnosis ( http://dpd.cdc.gov, 2013).

Clinical Manifestations

Patients infected with P. jiroveci have symptoms identical to pneumonia.  The patient may present with fever, chills, productive or dry cough, and malaise. P. jiroveci mostly infects immunocompromised individuals however individuals with intact immune systems can become infected as well. Infection may be caused by excessive steroid use, chronic antibiotic usage, and overexposure to infected particles.  A fungal infection is suspected when symptoms persist refractory to unsuccessful antibiotic therapy.  Chest x-rays are utilized to diagnose pneumonia.   Infiltration of fluid in the lungs is seen to determine pneumonia.  However x-rays do not determine the cause of the infiltration.  A biopsy with culture identification must be performed to determine the pathogenic microbe   (Chuang, et. al., 2007).                   

Fig 2: The sexual form of Pneumocystis in lung tissue stained with silver stain(Ammann, 2013, Interactive Health, 2013).

Proper identification of P jiroveci can be performed in a number of ways.  Samples can be taken from bronchoalveolar lavage fluid or lung biopsy (Botterel, et. al., 2012)  The samples can be stained and viewed under microscopy.  The samples can undergo a molecular method called Real Time PCR.  This is more sensitive by measuring the amount of P. jiroveci specific DNA in the sample (Botterel et al. 2012; Mc Taggart, et. al., 2012; and Samuel, et. al., 2011).

Other Species of Fungi Similar to P. jiroveci

This species of Pneumocystis is specificially found in primates and humans.  Similar species of Pneumocystis are found in other mammals and are not pathogenic to humans. For example,  P. carinii and P. wakefieldiae are pathogens of rats, P. murina are found in mice, and P. oryctolagi are found in rabbits.  The particular species is specific to its host.  It is suspected  these fungal  species coevolved with their host over the past 100 million years.  They lay in wait in healthy individuals until the host becomes immunocomprimised or is transmitted to an immunocompromised individual.  The current techniques for identification of these particular species are phylogenetic analysis and antigen specificity analysis.  Cross infection across different species is rare; and in some cases nonexistent.  A researcher can identify the isolate by host species (Aliouat-Denis et. al, 2008).

Case Studies

1.      A 43 year old female arrived at the hospital complaining of fever, dyspnea, and diffuse alveolar and interstitial infiltrations.  The patient has no pertinent past medical history and was recently diagnosed with community acquired pneumonia treated with the antibiotic Levofloxacin.  After the condition worsened, she went back to the hospital for treatment.  She received steroid treatments of cephatriaxone and dexamethasone with aminophilline antibiotics.  Still the condition persisted.  Her chest x-ray showed nodules and interstitial infiltrates.  Malignant bronchiolalveolar carcinoma was diagnosed.  The patient was admitted, intubated and placed on a ventilator.  Four days post admission Pneumocystis jirveci was identified by sputum culture and microscopy.  She tested negative for HIV infection.  The patient was treated with co-trimoxazole.  After 7 days with no improvement the family opted to remove her from the hospital where she died in her home (Chuang et. al., 2007).

2.      The second study, a 30 year old male was admitted to a hospital complaining of cough, productive cough, fever, chills and dyspnea, with an onset of 3 weeks.  The patient had oral candidiasis visible with oral examination.  The patient had elevated leukocytes in his blood count.  The chest x-ray showed infiltrations in the alveolar spaces of his lungs.   The patient was treated with ceftriaxone and erythromycin.  The patient’s condition worsened the next day and oxygen saturations decreased to 80%.  The patient had a recent history of 200mg prednisolone use for 1 month in duration for body building purposes.  His medication treatment was changed to ceftazidime, co-trimoxazole and vancomycin.  CT scan of the lungs showed cystic lesions present in the left lower lobe.  Bronchoscopy was performed and showed foamy eosinophylic foamy substances.  Eosinophiles are leukocytes responsible for combating parasitic and fungal infection.  A bronchoalveolar lavage was performed and cultured. Identification of P. jiroveci was confirmed by microscopy.  Medication treatment was continued and the patient recovered fully in 4 weeks (Tabarsi et. al., 2008).

References

1.     A. Aliouat-Denis, M. Chabe, C. Demanche, M, Aliouat, E. Viscogliosi, J. Guillot, L. Delhaes, and E. Dei-Cas, 2008, Pneumocystis species, co-evolution and pathogenic power, Infectious Genetic Evolution, Vol 5, pp. 708-726.

2.     Arthur Ammann, MD, 2013, Pneumocystis jiroveci (formerly carinii) pneumonia, http://www.hiv.va.gov/provider/image-library/pneumocystis-jiroveci.asp?post=1&slide=148.

3.     F. Botterel, O. Cabaret, F. Foulet, C. Cordonnier, J. Costa, & S. Bretagne, 2012, Clinical Significance of Quantifying Pneumocystis jirovecii DNA by Using Real-Time PCR in Bronchoalveolar Lavage Fluid from Immunocompromised Patients, Journal of Clinical Microbiology, Issue 50, vol. 2, pp. 227-231.

4.     C. Chuang, X. Zhanhong, G. Yinyin, Z. Qingsi, Z. Shuqing and Z. Nanshan, 2007, Unsuspected Pneumocystis pneumonia in  an HIV-seronegative patient with untreated lung cancer: circa case report,   Journal of Medical Case Reports, 1:115, pp. 1-5. 

5.     M. Cushion, 2010, Are Members of the Fungal Genus Pneumocystis (a) Commensals; (b) Opportunists; (c) Pathogens; or (d) All of the Above?, PLos Pathogens, vol. 6, Issue 9, pp 1-4.

6.     C. Demanche, M. Berthelemy, T. Petit, B. Polack, A. Wakefield, E. Dei-Cas, and J. Guillot, 2001, Phylogeny of Pneumocystis carinii from 18 Primate Species Confirms Host Specificity and Suggest Coevolution, Journal of Clinical Microbiology, vol 39, pp. 2126-2133.

7.     P. Hauser, F. Burdet, O. Cisse, L. Keller, P. Taffe, K. Sanglard, and M. Pagni, 2010, Comparative Genomics Suggests that the Fungal Pathogen Pneumoxystis is an Obligate Parasite Scabenging Amino Acids from its Host’s Lungs, PLoS ONE, vol. 5, issue 12, pp. 1-7.

8.     A. Limper, K. Knox, G. Sarosi, N. AMpel, J. Bennett, A. Catanzaro, S. Davies, W. Dismukes, C. Hage, K. Marr, C. Mody, J. Perfect, and D. Stevens, 2011, An official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients, American Journal of Respiratory Critical Care Medicine, vol. 183, pp. 96-128.

9.     L. Mc. Taggart, N. Wengenack, & S. Richardson, 2012, Validation of the MycAssay Pneumocystis Kit for Detection of Pneumocystis jirovecii in Bronchoalveolar Lavage Specimens by Comparison to a Laboratory Standard of Direct Immunofluorescence Microscopy, Real-Time PCR, or Conventional PCR, Journal of Clinical Microbiology, Issue 50, vol. 6, pp. 1856-1859.

10.  A. Morris & K. Norris, 2012, Colonization by Pneumocystis jirovecii and its Role in Disease, Clinical Microbiology Reviews, Issue 25, vol. 2, pp. 297-317.

11.  C. Samuel, A. Whitelaw, C. Corcoran, B. Morrow, N. Hsiao, M. Zampoli, & H. Zar, 2011, Improved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study, BioMed Central Infectious Diseases, Issue 11, vol. 329, pp. 1-6.

12.  J. Stringer, C. Beard, R. Miller, and  A. Wakefield,  2002, A New Name (Pneumocystis jiroveci) for Pneumonocystis from Humans, Emerging Infectious Diseases, vol. 8, no. 9, pp. 891-896.

13.  P. Tabarsi, M. Mirsaeidi, M. Amiri, S. Karimi, M. Masjedi, and K. Mansouri, 2008, Inappropriate use of steroid and Pneumocystis jiroveci pneumonia: report of two cases, Eastern Mediterranean Health Journal, vol. 14, no. 5, pp. 1217-1221.

14.  C. Thomas and A. Limper, 2007, Current insights into the biology and pathogenesis of Pneumocystis pneumonia, Nature Reviews Microbiology, vol. 5, pp 298-308.

U. S. Center for Disease Control, 2012, http://dpd.cdc.gov/dpdx/HTML/Pneumocystis.htm