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      Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study

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          Abstract

          Background

          Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and  -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.

          Methods

          Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.

          Results

          One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.

          Conclusion

          Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.

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          Most cited references31

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          Cytomegalovirus reactivation in critically ill immunocompetent patients.

          Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined. To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons. We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models. Association of CMV reactivation with prolonged hospital length of stay or death. The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log(10) copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days. These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.
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            Colonization by Pneumocystis jirovecii and its role in disease.

            Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.
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              Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome.

              In the next decade, longer survival of patients with cancer and more-aggressive therapies applied to common conditions, such as asthma and rheumatoid arthritis, will result in a larger population with significant immune system defects. Many in this population will be at risk for opportunistic infections, which are familiar to doctors who have treated people infected with human immunodeficiency virus (HIV). However, the epidemiology, presentation, and outcome of these infections in patients with an immune system defect, other than that caused by HIV infection, may be different than those encountered in patients with acquired immunodeficiency syndrome. Reviewed are 4 common opportunistic infections: Pneumocystis carinii pneumonia, cryptococcosis, atypical mycobacterial infection, and cytomegalovirus infection. Emphasized are the important differences among these groups at risk.
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                Author and article information

                Contributors
                damiani.celine@chu-amiens.fr
                Journal
                Ann Clin Microbiol Antimicrob
                Ann Clin Microbiol Antimicrob
                Annals of Clinical Microbiology and Antimicrobials
                BioMed Central (London )
                1476-0711
                20 January 2024
                20 January 2024
                2024
                : 23
                : 8
                Affiliations
                [1 ]Laboratoire de Parasitologie et Mycologie Médicales, Centre de Biologie Humaine, CHU Amiens-Picardie, ( https://ror.org/010567a58) 1 rond-point du Pr Cabrol, 80054 Amiens Cedex 1, France
                [2 ]Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, Université de Picardie Jules Verne, ( https://ror.org/01gyxrk03) 1 rue des Louvels, 80037 Amiens Cedex 1, France
                [3 ]Laboratoire de Virologie, Centre de Biologie Humaine, CHU Amiens-Picardie, ( https://ror.org/010567a58) 1 rond-point du Pr Cabrol, 80054 Amiens Cedex 1, France
                Article
                663
                10.1186/s12941-023-00663-2
                10800065
                38245721
                fb30973e-f3ec-4665-8a3e-02a3d38e4cad
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 June 2023
                : 21 December 2023
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Infectious disease & Microbiology
                pneumocystis jirovecii,pneumocystis pneumonia,pneumocystis pulmonary colonization,pulmonary coinfections,herpesviridae

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