Pneumcystisjirovecii is a pathogen that causes Pneumocystis pneumonia (PCP), an infection in (HIV/ADS) and other immunocompromised patients. The rare reports of P. jirovecii pneumonia in sub-Saharan Africa are controversial due to the high HIV/AIDS seropositivity. The study determined the significance of P. jirovecii in TB smear negative retreatment patients at the Coast General Teaching Referral Hospital-Mombasa. Sputum samples were subjected to toluidine blue O(TBO) stain for microscopy and polymerase chain reaction (PCR). A total of 100 TB smear negative participants were enrolled in the study and expectorated sputum was collected. Out of the 100 patients, 63 men and 37 women. Patients aged 31 to 53 made up 62% of the patients. The patients aged 31 to 53 made up 75% of the patients (Min = 11y, Max = 85y). The median age of the patients was 42 years. Nested PCR has a prevalence of 41% (41 instances). TBO staining has a prevalence of 29% (29 instances). Detecting an additional 13 more patients than toluidine O staining technique. The sensitivity of toluidine blue O staining was 33.82%, which indicates that it correctly identified 33.82% of true positive cases compared to PCR. The specificity of toluidine blue O staining was 97.82%, indicating that it had a high ability to correctly identify true negative cases compared to PCR, suggesting that it was good at ruling out non-P. jirovecii cases. The study confirms that P. jirovecii is as a significant cause of persistent symptoms in TB patients that could be responsible for persistent symptoms despite TB treatment. We recommend fungal diagnostics in such patients before retreatment.
References
[1]
Abouya, Y.L., Beaumel, A., Lucas, S., Dago-Akribi, A., Coulibaly, G., N’dhatz, M., et al. (1992) Pneumocystis carinii Pneumonia: An Uncommon Cause of Death in African Patients with Acquired Immunodeficiency Syndrome. American Review of Respiratory Disease, 145, 617-620. https://doi.org/10.1164/ajrccm/145.3.617
[2]
Apostolopoulou, A. and Fishman, J.A. (2022) The Pathogenesis and Diagnosis of Pneumocystis jiroveci Pneumonia. Journal of Fungi, 8, Article 1167. https://doi.org/10.3390/jof8111167
[3]
Bartlett, M.S. and Smith, J.W. (1991) Pneumocystis carinii, an Opportunist in Immunocompromised Patients. Clinical Microbiology Reviews, 4, 137-149. https://doi.org/10.1128/cmr.4.2.137
[4]
Bateman, M., Oladele, R. and Kolls, J.K. (2020) Diagnosing Pneumocystis jirovecii Pneumonia: A Review of Current Methods and Novel Approaches. Medical Mycology, 58, 1015-1028. https://doi.org/10.1093/mmy/myaa024
[5]
Bii, C.C., Kose, J., Taguchi, H., Amukoye, E., Ouko, T.T., Muita, L.C., et al. (2006) Pneumocystis jirovecii and Microbiological Findings in Children with Severe Pneumonia in Nairobi, Kenya. The International Journal of Tuberculosis and Lung Disease, 10, 1286-1291.
[6]
Calderonsandubete, E. (2002) Historical Perspective on Pneumocystis carinii Infection. Protist, 153, 303-310. https://doi.org/10.1078/1434-4610-00107
[7]
Carmona, E.M. and Limper, A.H. (2010) Update on the Diagnosis and Treatment of Pneumocystis Pneumonia. Therapeutic Advances in Respiratory Disease, 5, 41-59. https://doi.org/10.1177/1753465810380102
[8]
Chakaya, J.M., Bii, C., Ng’ang’a, L., Amukoye, E., Ouko, T., Muita, L., et al. (2004) Pneumocystis carinii Pneumonia in HIV/AIDS Patients at an Urban District Hospital in Kenya. East African Medical Journal, 80, 30-35. https://doi.org/10.4314/eamj.v80i1.8663
[9]
Chawla, K., Martena, S., Gurung, B., Mukhopadhyay, C., Varghese, G. and Bairy, I. (2011) Role of PCR for Diagnosing Pneumocystis jirovecii Pneumonia in HIV-Infected Individuals in a Tertiary Care Hospital in India. Indian Journal of Pathology and Microbiology, 54, 326-329. https://doi.org/10.4103/0377-4929.81624
[10]
Cushion, M.T. (2010) Are Members of the Fungal Genus Pneumocystis (a) Commensals; (b) Opportunists; (c) Pathogens; or (d) All of the Above? PLOS Pathogens, 6, e1001009. https://doi.org/10.1371/journal.ppat.1001009
[11]
Cushion, M.T., Linke, M.J., Ashbaugh, A., Sesterhenn, T., Collins, M.S., Lynch, K., et al. (2010) Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection. PLOS ONE, 5, e8524. https://doi.org/10.1371/journal.pone.0008524
[12]
De Armas Rodríguez, Y., Wissmann, G., Müller, A.L., Pederiva, M.A., Brum, M.C., Brackmann, R.L., et al. (2011) Pneumocystis jirovecii Pneumonia in Developing Countries. Parasite, 18, 219-228. https://doi.org/10.1051/parasite/2011183219
[13]
Eddens, T. and Kolls, J.K. (2014) Pathological and Protective Immunity to Pneumocystis Infection. Seminars in Immunopathology, 37, 153-162. https://doi.org/10.1007/s00281-014-0459-z
[14]
Ewig, S., Bauer, T., Schneider, C., Pickenhain, A., Pizzulli, L., Loos, U., et al. (1995) Clinical Characteristics and Outcome of Pneumocystis carinii Pneumonia in HIV-Infected and Otherwise Immunosuppressed Patients. European Respiratory Journal, 8, 1548-1553. https://doi.org/10.1183/09031936.95.08091548
[15]
Harris, J.R., Marston, B.J., Sangrujee, N., DuPlessis, D. and Park, B. (2011) Cost-Effectiveness Analysis of Diagnostic Options for Pneumocystis Pneumonia (PCP). PLOS ONE, 6, e23158. https://doi.org/10.1371/journal.pone.0023158
[16]
Helweg-Larsen, J., Jensen, J.S., Dohn, B., Benfield, T.L. and Lundgren, B. (2002) Detection of Pneumocystis DNA in Samples from Patients Suspected of Bacterial Pneumonia—A Case-Control Study. BMC Infectious Diseases, 2, Article No. 28. https://doi.org/10.1186/1471-2334-2-28
[17]
Homayouni, M.M., Behniafar, H., Mehbod, A.S.A., Mohammad-Sadeghi, M. and Maleki, B. (2017) Prevalence of Pneumocystis jirovecii among Immunocompromised Patients in Hospitals of Tehran City, Iran. Journal of Parasitic Diseases, 41, 850-853. https://doi.org/10.1007/s12639-017-0901-y
[18]
Huang, L. and Crothers, K. (2009) HIV‐Associated Opportunistic Pneumonias. Respirology, 14, 474-485. https://doi.org/10.1111/j.1440-1843.2009.01534.x
[19]
Huang, L., Morris, A., Limper, A.H. and Beck, J.M. (2006) An Official ATS Workshop Summary: Recent Advances and Future Directions in Pneumocystis Pneumonia (PCP). Proceedings of the American Thoracic Society, 3, 655-664. https://doi.org/10.1513/pats.200602-015ms
[20]
Kovacs, J.A. and Masur, H. (2009) Evolving Health Effects of Pneumocystis: One Hundred Years of Progress in Diagnosis and Treatment. JAMA, 301, 2578-2585. https://doi.org/10.1001/jama.2009.880
[21]
Minor, O.L., Germani, Y., Chartier, L., Lan, N.H., Lan, N.T.P., Duc, N.H., et al. (2008) Predictors of Pneumocystosis or Tuberculosis in HIV-Infected Asian Patients with AFB Smear-Negative Sputum Pneumonia. JAIDS Journal of Acquired Immune Deficiency Syndromes, 48, 620-627. https://doi.org/10.1097/qai.0b013e31817efb3c
[22]
Lowe, D.M., Rangaka, M.X., Gordon, F., James, C.D. and Miller, R.F. (2013) Pneumocystis jirovecii Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression. PLOS ONE, 8, e69969. https://doi.org/10.1371/journal.pone.0069969
[23]
Lu, Y., Ling, G., Qiang, C., Ming, Q., Wu, C., Wang, K., et al. (2011) PCR Diagnosis of Pneumocystis Pneumonia: A Bivariate Meta-Analysis. Journal of Clinical Microbiology, 49, 4361-4363. https://doi.org/10.1128/jcm.06066-11
[24]
Mohamed, A., Obanda, B.A., Njeri, H.K., Loroyokie, S.N., Mashedi, O.M., Ouko, T.T., et al. (2022) Serological Evidence of Chronic Pulmonary Aspergillosis in Tuberculosis Patients in Kenya. BMC Infectious Diseases, 22, Article No. 798. https://doi.org/10.1186/s12879-022-07782-9
[25]
Jarboui, M.A., Mseddi, F., Sellami, H., Sellami, A., Makni, F. and Ayadi, A. (2013) Genetic Diversity of Pneumocystis Jirovecii Strains Based on Sequence Variation of Different DNA Region. Medical Mycology, 51, 561-567. https://doi.org/10.3109/13693786.2012.744879
[26]
Morris, A. and Norris, K.A. (2012) Colonization by Pneumocystis jirovecii and Its Role in Disease. Clinical Microbiology Reviews, 25, 297-317. https://doi.org/10.1128/cmr.00013-12
[27]
Morris, A., Lundgren, J.D., Masur, H., Walzer, P.D., Hanson, D.L., Frederick, T., et al. (2004) Current Epidemiology of Pneumocystis Pneumonia. Emerging Infectious Diseases, 10, 1713-1720. https://doi.org/10.3201/eid1010.030985
[28]
Murray J.F. (2005) Pulmonary Complications of HIV-1 Infection among Adults Living in Sub-Saharan Africa. The International Journal of Tuberculosis and Lung Disease, 9, 826-835.
[29]
Mwaura, E.N., Matiru, V. and Bii, C. (2013) Mycological Findings of Sputum Samples from Pulmonary Tuberculosis Patients Attending TB Clinic in Nairobi, Kenya. Virology & Mycology, 2, Article 1000119. https://doi.org/10.4172/2161-0517.1000119
[30]
Nowaseb, V., Gaeb, E., Fraczek, M.G., Richardson, M.D. and Denning, D.W. (2014) Frequency of Pneumocystis jirovecii in Sputum from HIV and TB Patients in Namibia. The Journal of Infection in Developing Countries, 8, 349-357. https://doi.org/10.3855/jidc.3864
[31]
Onishi, A., Sugiyama, D., Kogata, Y., Saegusa, J., Sugimoto, T., Kawano, S., et al. (2012) Diagnostic Accuracy of Serum 1,3-β-D-Glucan for Pneumocystisjiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis. Journal of Clinical Microbiology, 50, 7-15. https://doi.org/10.1128/jcm.05267-11
[32]
Patel, N. and Koziel, H. (2004) Pneumocystisjiroveci Pneumonia in Adult Patients with AIDS: Treatment Strategies and Emerging Challenges to Antimicrobial Therapy. Treatments in Respiratory Medicine, 3, 381-397. https://doi.org/10.2165/00151829-200403060-00005
[33]
Rath, P. and Steinmann, J. (2014) Update on Diagnosis of Pneumocystis Pulmonary Infections. Current Fungal Infection Reports, 8, 227-234. https://doi.org/10.1007/s12281-014-0188-8
[34]
Reid, A.B., Chen, S.C.-A. and Worth, L.J. (2011) Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: New Risks and Diagnostic Tools. Current Opinion in Infectious Diseases, 24, 534-544. https://doi.org/10.1097/qco.0b013e32834cac17
[35]
Roux, A., Canet, E., Valade, S., Gangneux-Robert, F., Hamane, S., Lafabrie, A., et al. (2014) Pneumocystis jirovecii Pneumonia in Patients with or without AIDS, France. Emerging Infectious Diseases, 20, 1490-1497. https://doi.org/10.3201/eid2009.131668
[36]
Roux, A., Gonzalez, F., Roux, M., Mehrad, M., Menotti, J., Zahar, J.-R., et al. (2014) Update on Pulmonary Pneumocystis jirovecii Infection in Non-HIV Patients. Médecine et Maladies Infectieuses, 44, 185-198. https://doi.org/10.1016/j.medmal.2014.01.007
[37]
Russian, D.A. and Levine, S.J. (2001) Pneumocystis carinii Pneumonia in Patients without HIV Infection. The American Journal of the Medical Sciences, 321, 56-65. https://doi.org/10.1097/00000441-200101000-00009
[38]
Masur, H., Kovacs, J. and Siegel, M. (2016) Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection. Seminars in Respiratory and Critical Care Medicine, 37, 243-256. https://doi.org/10.1055/s-0036-1579556
[39]
Slogrove, A.L., Cotton, M.F. and Esser, M.M. (2009) Severe Infections in HIV-Exposed Uninfected Infants: Clinical Evidence of Immunodeficiency. Journal of Tropical Pediatrics, 56, 75-81. https://doi.org/10.1093/tropej/fmp057
[40]
Thomas, C.F. and Limper, A.H. (2004) Pneumocystis Pneumonia. New England Journal of Medicine, 350, 2487-2498. https://doi.org/10.1056/nejmra032588
[41]
Thomas, C.F. and Limper, A.H. (2007) Current Insights into the Biology and Pathogenesis of Pneumocystis Pneumonia. Nature Reviews Microbiology, 5, 298-308. https://doi.org/10.1038/nrmicro1621
[42]
Luísa Tomás, A. and Matos, O. (2018) Pneumocystis jirovecii Pneumonia: Current Advances in Laboratory Diagnosis. OBM Genetics, 2, Article 49. https://doi.org/10.21926/obm.genet.1804049
[43]
Toper, C., Rivaud, E., Daniel, C., Cerf, C., Parquin, F., Catherinot, É., et al. (2011) Pneumocystose pulmonaire chez des patients immunodéprimés non infectés par le VIH: Étude de 41 cas. Revue de Pneumologie Clinique, 67, 191-198. https://doi.org/10.1016/j.pneumo.2011.06.001
[44]
Tufa, T.B. and Denning, D.W. (2019) The Burden of Fungal Infections in Ethiopia. Journal of Fungi, 5, Article 109. https://doi.org/10.3390/jof5040109
[45]
Vargas, S.L., A. Ponce, C., Gigliotti, F., Ulloa, A.V., Prieto, S., Muñoz, M.P., et al. (2000) Transmission of Pneumocystis carinii DNA from a Patient with P. Carinii Pneumonia to Immunocompetent Contact Health Care Workers. Journal of Clinical Microbiology, 38, 1536-1538. https://doi.org/10.1128/jcm.38.4.1536-1538.2000
[46]
Vray, M., Germani, Y., Chan, S., Duc, N.H., Sar, B., Sarr, F.D., et al. (2008) Clinical Features and Etiology of Pneumonia in Acid-Fast Bacillus Sputum Smear-Negative HIV-Infected Patients Hospitalized in Asia and Africa. AIDS, 22, 1323-1332. https://doi.org/10.1097/qad.0b013e3282fdf8bf
[47]
Wakefield, A.E. (1996) DNA Sequences Identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. Hominis in Samples of Air SPORA. Journal of Clinical Microbiology, 34, 1754-1759. https://doi.org/10.1128/jcm.34.7.1754-1759.1996
[48]
Worodria, W., Okot-Nwang, M., Yoo, S.D. and Aisu, T. (2003) Causes of Lower Respiratory Infection in HIV-Infected Ugandan Adults Who Are Sputum AFB Smear-Negative. The International Journal of Tuberculosis and Lung Disease, 7, 117-123.
[49]
Zakrzewska, M., Roszkowska, R., Zakrzewski, M. and Maciorkow-Ska, E. (2019) Pneumocystis Pneumonia: Still a Serious Disease in Children. Journal of Mother and Child, 23, 159-162. https://doi.org/10.34763/devperiodmed.20192303.159162