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).
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.
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