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Eur J Cardiothorac Surg 2001;20:799-802
© 2001 Elsevier Science NL
a Service of Cardiology, Virgen del Rocio University Hospital, Seville, Spain
b Service of Internal Medicine, Virgen del Rocio University Hospital, Seville, Spain
c Service of Cardiovascular Surgery, Virgen del Rocio University Hospital, Seville, Spain
d Service of Microbiology, Virgen del Rocio University Hospital, Seville, Spain
Received 13 October 2000; received in revised form 22 June 2001; accepted 5 July 2001.
Corresponding author. Avda. Italia 41, 41710 Utrera, Sevilla, Spain. Tel.: +34-95-5860357
e-mail: sandube{at}cica.es
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Pneumocystis carinii • Heart transplant • Prophylaxis • Epidemiology
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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In spite of the high prevalence of PC pneumonia in immunocompromised patients, little is known about the epidemiological characteristics, transmission process and sources of this infection, and whether the cases of PC pneumonia in subjects with immunosuppressive therapy are the result of the reactivation of a latent infection or to a due to a recent infection is unknown.
The aim of this study was to provide information about the epidemiological characteristics of PC pneumonia in a cohort of HT recipients when compared with the epidemiology of PC infection in a cohort of chronic sputum producers (CSP) representative of the general population of the same geographical area.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The general methodology of the transplant procedure was standard and has been described previously [10]. In summary, the immunosuppressive regimen consisted of induction with OKT3 and maintenance with cyclosporin A, azathioprine, and corticosteroids. Doses of cyclosporin were targeted to achieve a plasma level of 200–400 ng/ml during the first month posttransplantation. Thereafter, levels of 100–200 ng/ml were targeted. Rejection episodes were diagnosed by endomyocardial biopsy and treated with intravenous boluses of methylprednisolone. Prophylaxis against toxoplasmosis (6 weeks of pyrimethamine, 25 mg/day, plus folinic acid) was administered in all cases, but anti-PC prophylaxis (6 months of trimethoprim–sulfamethoxazole (TMP-SMX), 160–800 mg 3 days/week) was not introduced until 1993.
CSP were younger than 66 years on entry to the cohort because it is the limit for HT in our cardiac transplant program. All subjects in this group denied being at risk for HIV infection and no other reason could be found for immunosuppression. A commercial enzyme immunoassay (EIA; Abbot Laboratories, N. Chicago, IL) did not detect HIV-1 infection in either group.
Upon clinical and radiological findings of pulmonary infection, definitive PC pneumonia diagnosis in HT recipients was accepted only after demonstration of the microorganism's presence in respiratory secretions or lung tissue. The presence of PC in CSP was investigated in sputum samples following the protocol described previously [11]. Clinical specimens were simultaneously assayed by four different methods in order to improve the specificity of the test: toluidine blue O stain, modified Giemsa stain, methenamine silver stain and immunofluorescence with monoclonal antibodies (Pneumo-cell IF test; Cellabs, Brookvale, Australia). Identification was considered positive for PC when the parasite was detected by all four techniques.
The differences in the study variables were assessed using the Student's t-test and Pearson's Chi-square test for categorical variables. All analyses were done using the Statistical Package for Social Studies (SPSS) software, version 5.0 (SPSS, Inc., Chicago, IL).
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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During the study period, four (5.5%) of the 72 HT recipients developed PC pneumonia, but one had two episodes. In these subjects, the causes leading to HT were ischemic cardiopathy (two cases) and idiopathic dilated myocardiopathy (two cases). One patient had diabetes before transplantation. PC pneumonia was diagnosed at days 53, 102, 230 and 181 after HT. In the last patient, a second PC pneumonia episode occurred at day 772 after HT, i.e. 19 months after the first episode. Only one had received primary TMP-SMX prophylaxis, but developed PC pneumonia 2 months after discontinuing prophylactic therapy. None of the patients received secondary prophylaxis. All four patients who were diagnosed as having PC pneumonia were successfully treated with a standard dose of TMP-SMX (20 mg/kg per day for 21 days). Two of these four subjects had CMV infection and all of them had at least one episode of acute rejection. No patient developed PC pneumonia while receiving TMP-SMX prophylaxis.
Sputum analyses of 34 CSP identified two (5.8%) subjects as carriers of PC. No significant differences were found when the accumulative incidences of PC pneumonia in HT patients and PC infection in CSP were compared (P=0.7). The mean age was significantly lower in the first group (50±9 vs. 57±9, P<0.001). Sex distribution was comparable in both groups. The general characteristics of HT patients with PC pneumonia and PC carrier subjects are shown in Table 1.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The classic pathogenic hypothesis that PC remains latent in the lung after primary infection is supported by the high prevalence of PC antibodies detectable at an early age and persisting for life in normal persons [12], and by the occurrence of PC pneumonia with the advent of immunosuppression [13]. However, PC appeared to be cleared from the lungs of 75% of animals within 1 year after an episode of PC pneumonia [14], implying that persistence of latent organisms is limited. Moreover, depletion of CD4+ cells in reconstituted severed combined immunodeficiency mice that had resolved PC pneumonia failed to reactivate the infection [15]. On the other hand, despite effective prophylaxis, recurrent episodes of PC pneumonia are relatively common in HIV-infected patients, and molecular studies have shown that genetically distinct isolates were associated with each episode of PC pneumonia [16]. Furthermore, recurrent PC colonization in lung and heart–lung transplant recipients on long-term TMP-SMX prophylaxis has been reported [17,18]. These cumulative data support the concept that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection resulting from exposure to exogenous sources of PC through contact with environmental sources or infected persons.
In HT recipients, the knowledge of the exact moment at which the immunosuppression is started and the possibility of controlling the intensity and duration of the immunosuppressive therapy provided an appropriate situation to appraise whether PC pneumonia represents a reactivation of a latent infection or whether it is a primary PC infection taking advantage of the immunosuppression. If the hypothesis of reactivation was true, the period of highest risk for PC pneumonia would be the first 2 months posttransplantation, when the immunosuppressive therapy is most intense. However, most of our patients developed PC pneumonia after this period, and in one case, a second PC pneumonia episode occurred 2 years after HT. Moreover, in our study, the frequency of PC pneumonia in HT recipients and PC infection in CSP is the same, suggesting that a similar rate of exposition to the parasite in both groups might lead to the development of an opportunistic disease (HT recipients) or a subclinical infection (CSP), depending on the status of the immune system. These results, together with those of others [14–18], reinforce the notion that PC pneumonia that occurs in immunocompromised patients is probably the result of infection by exogenous PC.
Knowledge on the natural history of PC infection is important to design the strategies of prophylaxis in patients who receive maintenance immunosuppressive treatment. TMP-SMX prophylaxis in HT reduces the incidence of PC pneumonia to nearly zero [19], but it is effective only as long as it is administered [20]. Currently, most authors recommend universal prophylaxis during the first 2–4 months posttransplantation, while others select only high-risk patients [19]. Unlike HIV-infected patients with CD4+ lymphocyte counts of <200/µl or those with <14% CD4+ lymphocytes who define subjects at risk, the risk of PC pneumonia in immunocompromised patients without AIDS, including solid organ transplant recipients, cannot be accurately quantified at present, and clinically useful biological markers that guide the initiation of chemoprophylaxis are not available [21,22]. However, the primary risk for PC and other opportunistic infections in solid organ transplant recipients is the ‘net state of immunosuppression’, to which a number of factors contribute, including the total amount of previous and current immunosuppressive treatments, the presence of acute and chronic graft rejection, and the presence of concomitant infections, especially those due to CMV [23].
In our study, the occurrence of PC pneumonia lasting more than 4 months in posttransplantation patients was common, and the frequency of PC carriers in the general population was relatively high. Although the role of these PC carriers in the transmission of PC to immunocompromised patients is yet to be deduced, our results argue for the convenience of continuous anti-PC chemoprophylaxis, at least in areas where the prevalence of PC infection is high. Further investigation is needed to ascertain the relative risk of PC infection and the optimal duration of anti-PC prophylaxis in each area.
In conclusion, the results of this and other studies [14–18] strongly support the hypothesis that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection resulting from exposure to exogenous sources of PC through contact with infected persons or other environmental sources rather than through reactivation of a latent organism. Therefore, chemoprophylaxis against PC in areas where the prevalence of PC infection is high could be continuous, at least to patients at the highest risk, such as those with recurrent or chronic rejection and following onset of CMV infection.
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Acknowledgments |
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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ez-Roldan A. Presence of glomerular basement membrane antibodies in HIV-negative patients with Pneumocystis carinii pneumonia. Clin Exp Immunol 1997;107:448-450.[Medline]
This article has been cited by other articles:
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  L. U. Nwakanma, A. S. Shah, J. V. Conte, and W. A. Baumgartner Heart Transplantation Card. Surg. Adult, January 1, 2008; 3(2008): 1539 - 1578. [Full Text]
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