Presented by Sarah E. Johnston

1. Opportunistic Fungal infections that can occur in HIV infected individuals Presented by Sarah E. Johnston

2. Overview • HIV effects on immune system • potential fungal pathogens of HIV patients • Pneumonocystisjirovecii and the disease PCP • Cryptococcus neoformansand fungal meningitis • Summary • Questions

3. Severely debilitates the human immune system by: • Defecting Macrophage’s ability to properly process and present foreign particles to immune system • Debilitate and deplete CD4+ T lymphocytes needed for cytokine production and assisting B cells to produce antibodies • Debilitated cytokine production effect neutrophil count and function Human Immunodeficiency Virus (HIV-1 & 2)

4. Rhizopusoryzae Opportunistic Offenders Pneumonocystisjirovecii Candida albicans Aspergillusfumigatus Cryptococcus neoformans

5. Pneumonocystisjirovecii • Was formerly known as Pneumonocystiscariniiand thought to be a protozoan. • Life cycle has both sexual and asexual components http://holtsbioclass-pneumocystis-jirovecii.blogspot.com/ http://armymedical.tpub.com/MD0842/MD08420072.htm Interesting fact: % 80 U.S. population has antibodies to this organism Uninucleatesporocyst Cyst http://www.ppdictionary.com/mycology/jiroveci.htm

6. Pneumonocystiscarinii pneumonia (PCP) • The trophozoite form attaches to lung epithelial cells after inhalation • P. jiroveci replicates extracellularly and impairs oxygen diffusion • Inflammation causes host cell to lysis. • Damage to the lung basement membrane generates a characteristic foamy exudate and interstitial leukemic infiltration in the alveoli, resulting in a decrease in alveolar capillary permeability.

7. How it is diagnosed • Diagnosis use to be based on stained respiratory tissues using Giemsa and Gomori-Grocott techniques, staining sputum, branchoalveolar fluid or lung tissue. • Due to inability to properly visualize trophozoite form PCR is the standard technique used to identify this pathogen. http://www.cito-latam.com/page/microfotografias/id/81/title/BAL-Pneumocystis-Jiroveci-II

8. How HIV contributes to risk • Fortunately due to the use HAART (highly active antiretroviral therapy) PCP cases in HIV patients has decreased significantly. • HIV individuals who have progressed to full blown AIDS have a very low CD4+ T cell count. This contributes to decreased ability to produce super oxygen radicals used by alveolar macrophages to kill foreign invaders that they take up via phagocytosis.

9. Cryptococcus neoformans • Encapsulated Yeast-like fungus that belongs to the family Tremellaceae. • Transmission occurs via inhalation of basidiospores into the lungs. • Replication occurs via budding http://www.bmolchem.wisc.edu/labs/hull/research.html http://www.pnas.org/content/99/5/3165/F1.expansion.html

10. Fungal Meningitis • Is the inflammation of the membrane that surrounds the brain and spinal cord. • C. neoformans infections usually start in the lungs (pneumonia) and in HIV patients dissemination occurs to other areas. In this case to the CNS. http://en.wikipedia.org/wiki/Cryptococcus_neoformans http://www.life-worldwide.org/fungal-diseases/cryptococcus-neoformans/

11. Secondary infections • HIV patients with fungal meningitis usually develop a secondary infection site of the skin, prostate, and eye. • Secondary infection of the prostate can contribute to acting as a reservoir in AIDs patients and contributing to relapse in previoulsy treated patients. http://www.studyblue.com/notes/note/n/fungi/deck/854908 http://eyepathologist.com/disease.asp?IDNUM=303910

12. Different media used to culture C. neoformans • India ink is used in CSF to visualize capsule and creates characteristic halo effect around capsule • Bird seed agar- C. neoformansis brown in color due to uptake of brown pigment I media • Colonies are mucoid and cream colored on SAB http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Yeasts/Cryptococcus/C_neoformans.html http://thunderhouse4-yuri.blogspot.com/2010/09/cryptococcus-neoformans.html

13. Diagnosis of C. neoformansinfection • can be made by microscopic examination and/or culture of tissue or body fluids such as blood, cerebrospinal fluid, and sputum. • cryptococcal antigen test can rapidly test blood and/or cerebrospinal fluid to make the diagnosis. • A fungal culture is essential to differentiate between the different species of Cryptococcus - C. neoformans and C. gatti http://www.cdc.gov/fungal/cryptococcosis-neoformans/diagnosis.html

14. Summary • HIV critically impairs immune system and leaves it vulnerable to opportunistic fungal pathogens. • Pneumocystisjirovecii causes Pneumocycsticcarinii pneumonia (PCP) in AIDs patients and use to be a common indicator of HIV • Crypotococcusneoformansis the leading cause of fungal meningitis and is one of the most common opportunistic infections in individuals with AIDs

15. References • Shors, Teri.(2013). Understanding Viruses. 2nd edition, Chapter16 Human Immunodeficiency Virus (HIV) (pp.484-523).Burlington, MA: Jones and Bartlett Learning. • NIH. (April 03, 2012).NIH HIV/AIDS Overview. Retrieved from http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Pages/whatareHIVAIDS.aspx • Ayyavoo, V., et al.(1997).HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor κB.Natural Medicine.3.1117-1123. • Wagner, E. K., M. J. Hewlett. (2004). Basic Virology 2nd edition, Chapter 20Retroviruses:Converting RNA to DNA (pp. 356-376). Malden, MA: Blackwell Science Ltd. • Orenstein, J. M., Fox, C., and S. M. Wahl.(1997, June).Macrophages as a Source of HIV During Opportunistic Infections.Science.276.1857-1861. • CDC.( May 6, 2013). CDC. C. neoformanscryptococcosis. Retreived from http://www.cdc.gov/fungal/cryptococcosis-neoformans/ • Phair, J., et al.(1990). The Risk Of PNEUMOCYSTIS CARINII PNEUMONIA Among Men with Human Immunodefifiency Virus Type 1. The New England Journal of Medicine. 322.161-165. • Wilkin, A. and J. Feinberg.(1999, October). Pneumocystiscarinii Pneumonia: A Clinical Review.American Family Physician.60.1699-1708. • Sepkowitz, K.(2002, April). Opportunistic Infections in Patients with and Patients without Acquired Immunodeficiency Syndrome. Immunocompromised Hosts.34.1098-1107. • Murray, P. R., Rosenthal, K. S., and M. A. Pfaller. (2009). Medical Microbiology 6th edition, Chapter 74Opportunistic Mycoses(pp. 751-773). Philadelphia, PA: Mosbey Elsevier. • Kendrick, B.(1992). The Fifth Kingdom 3rd edition, Chapter 23 Medical Mycology(pp.327-333).Newburyport, MA. Focus Publishing. • Mitchell. T. G., and J. R. Perfect.(1995).Cryptococcosis in the Era of AIDS-100 years after the Discovery of Cryptococcus neoformans.Clinical Microbiology Reviews.8.515-548. • Maurya, V., et al.(2013).Oropharyngeal candidiasis and Candida colonization in HIV positive patients in northern India.Journal of Infectious Diseases in Developing Countries.7.608-613. • Latge, J.P.(1999). Aspergillus fumigates and Aspergillosis.Clinical Microbiology Reviews.12.310-350. • The University of Adeliade.(November 11 2013).Mycology Online : Zygomycetes. Retrieved from http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Zygomycetes/ • LSU.(April 26 2004). Mucology at LSU: Phycomycosis. Retreived from http://lsb380.plbio.lsu.edu/Highway%20markers%20folder/Phycomycosis.html • Van den Berk, G, et al.(2006). A fatal pseudo-tumour: disseminated basidiobolomycosis .BMC infectious diseases.6.140.