J.M. Varela

Pneumocystis jirovecii in General Population

P. jirovecii colonization can be frequently detected in immunocompetent adults, which suggests that the general population could be a source of this infection.

Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease Who Are Colonized with Pneumocystis jiroveci

In chronic obstructive pulmonary disease, high levels of airway and systemic inflammatory markers are associated with a faster decrease in lung function. Our study shows that patients colonized by Pneumocystis jiroveci have higher proinflammatory cytokine levels than do noncolonized patients. This suggests that Pneumocystis may play a role in disease progression.

Pneumocystis jiroveci genotypes in the Spanish population.

This study describes the genotype distribution of Pneumocystis jiroveci in 79 respiratory samples obtained from 15 patients with acquired immunodeficiency syndrome (AIDS) with P. jiroveci pneumonia and 64 human immunodeficiency virus-negative subjects with different chronic pulmonary diseases. The genotyping was based in analysis of 2 independent genetic loci: the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) fragment (assessed by direct sequencing) and the gene for dihydropteroate synthase (DHPS; assessed by restriction fragment-length polymorphism). The mt LSU rRNA analysis revealed the presence of 3 different polymorphisms for both populations. The major genotype, 85C/248C, was found to be significantly higher in patients with AIDS and P. jiroveci pneumonia than in patients with pulmonary disease. The rate of genotypes 85A/248C and 85T/248C was similar in both groups. The analysis of DHPS genotypes assesses the prevalence of its 4 possible genotypes, with 35.5% of genotypes related to sulfa resistance. The data suggest a common source of infection between both groups.

Association Between Bacteremia Due to Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis I) and Colorectal Neoplasia: A Case-Control Study

BACKGROUND The association between bacteremia by Streptococcus gallolyticus subsp. gallolyticus (SGG) and colorectal neoplasia (CRN) is well established but the frequency of the association varies widely in different studies. We conducted a case-control study to assess the association between SGG bacteremia and CRN. METHODS An analysis of all SGG bacteremias was performed during the period 1988-2011. The frequency of CRN in patients with SGG bacteremia was compared with the frequency of CRN in a symptomatic control group of patients matched at a 1:2 ratio for gender and age (±3 years) without S. bovis bacteremia and personal history of CRN and with increased risk of CRN (by the presence of symptoms, signs, or test suspicious of colonic pathology or by family history of CRN). RESULTS One hundred nine cases of SGG bacteremia were detected (mean age, 66 years; 87% male). Colonoscopy was performed in 98 cases, diagnosing 69 cases of CRN: 57 adenomas (39 advanced adenomas) and 12 invasive carcinomas. Only 4 cases had suspected CRN before the blood culture. The prevalence of CRN was higher in patients with SGG bacteremia than in the 196 control patients (70% vs 32%; odds ratio [OR], 5.1; 95% confidence interval [CI], 3.0-8.6). This difference was not significant when comparing nonadvanced adenomas (19% vs 12%), but we found significant differences in advanced adenomas (40% vs 16%; OR, 3.5; 95% CI, 2.0-6.1) and invasive carcinomas (12% vs 5%; OR, 2.9; 95% CI, 1.2-6.9). CONCLUSIONS The frequency of CRN among SGG infected patients is significantly increased compared with symptomatic age-matched controls, indicating that SGG infection is a strong indicator for underlying occult malignancy.

Pneumocystis jiroveci isolates with dihydropteroate synthase mutations in patients with chronic bronchitis

Since mutations in the dihydropteroate synthase (DHPS) gene possibly associated with sulfonamide resistance have been reported in patients with Pneumocystis jiroveci (previously carinii) pneumonia, and since P. jiroveci colonization has been recently demonstrated in patients with chronic pulmonary diseases, the present study aimed to investigate the possible occurrence of P. jiroveci DHPS mutations in patients with chronic bronchitis. P. jiroveci colonization was detected in 15 of 37 non-selected patients with chronic bronchitis by amplifying the large subunit of the mitochondrial gene of the ribosomal RNA using nested PCR. DHPS mutations were demonstrated using touchdown PCR and restriction enzyme analysis in two of eight patients with chronic bronchitis and in two of six patients from the same region who had AIDS-associated Pneumocystis pneumonia. In all cases, mutations were observed in subjects with no prior exposure to sulfonamides. These data could have important implications for public health, since (i) P. jiroveci colonization could speed the progression of chronic bronchitis, and (ii) these patients, who are customary sputum producers, could represent a reservoir for sulfonamide-resistant strains with the potential ability to transmit them to immunocompromised hosts susceptible to Pneumocystis pneumonia.

Pneumocystis jirovecii transmission from immunocompetent carriers to infant.

We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child.

Pneumocystis jirovecii colonization in patients treated with infliximab

Eur J Clin Invest 2011; 41 (3): 343–348

Pneumocystis carinii pneumonia in heart transplant recipients

OBJECTIVES In spite of the high prevalence of Pneumocystis carinii (PC) pneumonia in immunocompromised patients, little is known about the epidemiological characteristics of this infection, and whether the cases of PC pneumonia in immunosuppressed patients are the result of a reactivation of a latent infection or 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 heart transplant (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. METHODS We identified all the cases of PC pneumonia in the cohort of 72 subjects who underwent cardiac transplantation at our institution between January 1991 and December 1996 and compared them with the cases of PC infection identified in a non-selected cohort of 34 CSP. This second group was included to obtain an approximation of the frequency of PC carriers in the general population. Identification of PC was accomplished through customary stain techniques and immunofluorescence with monoclonal antibodies. RESULTS Of the 72 HT recipients four (5.5%) developed PC pneumonia, but one had two episodes. Only one had received primary chemoprophylaxis, but developed PC pneumonia 2 months after discontinuing prophylactic therapy. PC pneumonia episodes were produced 53, 102, 230, 181 and 772 days after the moment of transplant, respectively. PC was identified in two (5.8%) of the 34 CSP. 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). CONCLUSIONS The frequency of PC pneumonia among HT patients is the same as the frequency of PC infection in the general population. This observation and the long interval between transplantation and the development of PC pneumonia observed in the study support the hypothesis that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection rather than from the reactivation of latent organisms. Therefore, continuous prophylaxis might be indicated in areas with a high prevalence of PC for patients at highest risk.

Geographical variation in serological responses to recombinant Pneumocystis jirovecii major surface glycoprotein antigens

The use of recombinant fragments of the major surface glycoprotein (Msg) of Pneumocystis jirovecii has proven useful for studying serological immune responses of blood donors and human immunodeficiency virus (HIV)-positive (HIV(+)) patients. Here, we have used ELISA to measure antibody titres to Msg fragments (MsgA, MsgB, MsgC1, MsgC3, MsgC8 and MsgC9) in sera isolated in the USA (n=200) and Spain (n=326), to determine whether geographical location affects serological responses to these antigens. Blood donors from Seville exhibited a significantly greater antibody titre to MsgC8, and significantly lower responses to MsgC3 and MsgC9, than did Cincinnati (USA) donors. Spanish blood donors (n=162) also exhibited elevated responses to MsgC1, MsgC8 and MsgC9 as compared with Spanish HIV(+) (n=164) patients. HIV(+) patients who had Pneumocystis pneumonia (PcP(+)) exhibited a higher response to MsgC8 than did HIV(+) PcP(-) patients. These data show that geographical location plays a role in responsiveness to Msg fragments. Additionally, these fragments have utility in differentiating HIV(+) PcP and HIV(+) PcP(+) among patient populations.

Usefulness of oropharyngeal washings for identifying Pneumocystis jirovecii carriers.

PNEUMOCYSTIS jirovecii is the causative agent of Pneumocystis pneumonia (PcP), one of the most frequent and severe opportunistic infections in immunocompromised patients (Stringer et al. 2002). The incidence of PcP has decreased among AIDS patients in developed countries due to chemoprophylaxis and highly active anti-retroviral therapy (HAART). However, PcP remains an important cause of morbidity and mortality worldwide (Morris et al. 2004). Today, the interest in P. jirovecii infection is not only confined to patients with AIDS. It also represents a common and serious opportunistic infection in other immunodeficient groups such as those with autoimmune diseases as well as solid organ transplant recipients and cancer patients undergoing immunosuppressive therapy (Calderón et al. 2004a). Recent studies also demonstrated the presence of asymptomatic P. jirovecii colonization in patients with chronic pulmonary diseases (Respaldiza et al. 2005; Vidal et al. 2006). Despite the advances made in understanding human Pneumocystis infection, many aspects about its epidemiology and natural history remain unclear. For decades, diagnosis of PcP has relied on microscopic visualization of organisms in specimens obtained from the lung either by bronchoalveolar lavage (BAL) or by sputum induction. Currently, the ‘‘gold standard’’ for diagnosis of PcP involves using traditional cytochemical stains of BAL fluid and bright-field light microscopy. Fluorescence microscopy using immunofluorescent monoclonal antibodies enables greater sensitivity and specificity and is useful for analyzing induced-sputum samples (Elvin et al. 1988). Polymerase chain reaction amplification of P. jirovecii DNA increases sensitivity of detecting the organism and is used on sputum and BAL specimens containing only small numbers of organisms (Durand-Joly et al. 2005; Leibovitz et al. 1995). However, non-invasive procedures are sometimes needed when bronchoscopy or even sputum induction are difficult to perform, contraindicated, or unpleasant to the patient. Recently, PCR of oral washings was found to be an attractive non-invasive alternative method for diagnosing P. jirovecii infection. Oropharyngeal washings (OW) are obtained by having the patient rinse the mouth and gargle the throat using sterile saline. (Wakefield et al. 1993) first reported detecting P. jirovecii DNA by PCR by analyzing oral wash samples obtained from PcP patients. Subsequently, other workers have shown that oral or oropharyngeal lavage specimens are useful for diagnosing PcP in patients with severe respiratory distress or tendency to bleed who are unable to undergo bronchoscopy (Helweg-Larsen et al. 1997; Martino et al. 1999). The aim of this study was to evaluate PCR methods for efficacy in detecting P. jirovecii by analyzing OW samples from individuals without PcP but might harbor the organism. MATERIAL AND METHODS