E. Calderón

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 jirovecii multilocus genotyping profiles in patients from Portugal and Spain

Pneumonia caused by the opportunistic organism Pneumocystis jirovecii is a clinically important infection affecting AIDS and other immunocompromised patients. The present study aimed to compare and characterise the frequency pattern of DNA sequences from the P. jirovecii mitochondrial large-subunit rRNA (mtLSU rRNA) gene, the dihydropteroate synthase (DHPS) gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA operon in specimens from Lisbon (Portugal) and Seville (Spain). Total DNA was extracted and used for specific molecular sequence analysis of the three loci. In both populations, mtLSU rRNA gene analysis revealed an overall prevalence of genotype 1. In the Portuguese population, genotype 2 was the second most common, followed by genotype 3. Inversely, in the Spanish population, genotype 3 was the second most common, followed by genotype 2. The DHPS wild-type sequence was the genotype observed most frequently in both populations, and the DHPS genotype frequency pattern was identical to distribution patterns revealed in other European studies. ITS types showed a significant diversity in both populations because of the high sequence variability in these genomic regions. The most prevalent ITS type in the Portuguese population was Eg, followed by Cg. In contrast to other European studies, Bi was the most common ITS type in the Spanish samples, followed by Eg. A statistically significant association between mtLSU rRNA genotype 1 and ITS type Eg was revealed.

Efficacy and safety of dipyrone versus tramadol in the management of pain after hysterectomy: A randomized, double-blind, multicenter study

Background and Objectives We assessed the efficacy and safety of dipyrone in comparison with tramadol in the relief of early postoperative pain following abdominal hysterectomy. Methods A total of 151 women between 18 and 60 years of age undergoing abdominal hysterectomy during general anesthesia participated in a randomized, double-blind, controlled, multicenter study. Seventy-three patients received dipyrone and 78 received tramadol. Patients received an intravenous loading dose of the study drug immediately after operation followed by intravenous (IV) maintenance infusion and IV on-demand boluses up to a maximum number of predetermined doses/day of 8 g dipyrone and 500 mg tramadol. The duration of the study was 24 hours. Results The mean (SD) number of boluses in the dipyrone group was 3.8 (2.4) and 3.5 (2.5) in the tramadol group (95% confidence interval, −0.455 to 1.175), and the percentage of patients requiring rescue IV morphine (dipyrone 26.9%, tramadol 26.8%) was not statistically significant. Other analgesic efficacy parameters, such as pain intensity differences, sum of pain intensity differences, pain relief assessed by the patient, or patients who required the maximum number of demand doses, were not different between treatment groups. A significantly higher percentage of adverse gastrointestinal effects was found in patients given tramadol (42.1%) than in patients given dipyrone (20.2%) (P < .05). Also, a significantly higher number of tramadol-treated patients required ondansetron to control nausea and vomiting at 1 hour (19% v 7%), 2 hours (26% v 11%), and 24 hours (46% v 29%) (P < .05) after surgery. Patients and the investigators reported similar tolerability for both study arms. Conclusions Dipyrone and tramadol showed similar efficacy for early pain relief after abdominal hysterectomy. Nausea and vomiting, possibly caused by the tramadol, occurred more frequently in those patients. In this group, the need of the antiemetic drug ondansetron was also higher.

Pneumocystis jirovecii colonization in patients treated with infliximab

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

Trends in the prevalence and distribution of HTLV-1 and HTLV-2 infections in Spain

BackgroundAlthough most HTLV infections in Spain have been found in native intravenous drug users carrying HTLV-2, the large immigration flows from Latin America and Sub-Saharan Africa in recent years may have changed the prevalence and distribution of HTLV-1 and HTLV-2 infections, and hypothetically open the opportunity for introducing HTLV-3 or HTLV-4 in Spain. To assess the current seroprevalence of HTLV infection in Spain a national multicenter, cross-sectional, study was conducted in June 2009.ResultsA total of 6,460 consecutive outpatients attending 16 hospitals were examined. Overall, 12% were immigrants, and their main origin was Latin America (4.9%), Africa (3.6%) and other European countries (2.8%). Nine individuals were seroreactive for HTLV antibodies (overall prevalence, 0.14%). Evidence of HTLV-1 infection was confirmed by Western blot in 4 subjects (prevalence 0.06%) while HTLV-2 infection was found in 5 (prevalence 0.08%). Infection with HTLV types 1, 2, 3 and 4 was discarded by Western blot and specific PCR assays in another two specimens initially reactive in the enzyme immunoassay. All but one HTLV-1 cases were Latin-Americans while all persons with HTLV-2 infection were native Spaniards.ConclusionsThe overall prevalence of HTLV infections in Spain remains low, with no evidence of HTLV-3 or HTLV-4 infections so far.

Drug resistance mutations in patients infected with HIV-2 living in Spain

BACKGROUND In contrast with HIV-1, information about drug resistance in HIV-2 is scarce and mainly derived from small series of patients failing antiretroviral therapy. METHODS The spectrum of changes in the reverse transcriptase (RT), protease (PR) and integrase (INT) genes was examined in HIV-2 individuals enrolled in the HIV-2 Spanish register. RESULTS From a total of 236 HIV-2-infected individuals registered in Spain from 1989 to June 2010, 53 PR, 44 RT and 8 INT sequences were obtained. Low plasma viraemia precluded collection of this information from most of the remaining cases. No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I and K219E). In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations. In PR the most frequent major changes were V47A (17%), I54M (17%), I82F (13%), L90M (29%) and L99F (29%). Two of the three patients who failed on raltegravir had N155H in the INT region. CONCLUSIONS Drug resistance mutations in HIV-2 are selected at the same positions as in HIV-1, although with different frequency. Polymorphisms in the RT and PR associated with drug resistance in HIV-1 as compensatory changes are common in untreated HIV-2 subjects. These findings highlight the need for specific guidelines for interpreting genotypic resistance patterns in HIV-2 infection.

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.

Pneumocystis jirovecii colonization in chronic pulmonary disease

Pneumocystis jirovecii causes pneumonia in immunosuppressed individuals. However, it has been reported the detection of low levels of Pneumocystis DNA in patients without signs and symptoms of pneumonia, which likely represents colonization. Several studies performed in animals models and in humans have demonstrated that Pneumocystis induces a local and a systemic response in the host. Since P. jirovecii colonization has been found in patients with chronic pulmonary diseases it has been suggested that P. jirovecii may play a role in the physiopathology and progression of those diseases. In this report we revise P. jirovecii colonization in different chronic pulmonary diseases such us, chronic obstructive pulmonary disease, interstitial lung diseases, cystic fibrosis and lung cancer.

Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

ABSTRACT This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii.

Prevention of Pneumocystis pneumonia in patients with inflammatory bowel disease based on the detection of Pneumocystis colonization

To the Editor: The review of Poppers and Scherl1 raises an important issue concerning the prophylaxis against Pneumocystis pneumonia (PcP) in patients with inflammatory bowel disease (IBD) treated with immunosuppressive drugs. Currently, there are no guidelines and no standard of care for the chemoprophylaxis against PcP for IBD patients undergoing immunosuppressive therapies. PcP prophylaxis remains a case-by-case clinical decision balancing risk and benefits for each individual patient. Effective and relatively safe chemoprophylaxis for PcP is available, but it should be used with discretion to avoid exposing patients to unnecessary adverse side effects. Trimethoprim-sulfamethoxazole (co-trimoxazole) is the agent of choice for the prevention of PcP. Co-trimoxazole is generally well tolerated by patients without HIV infection, although rash, fever, and myelosuppression occur occasionally. Alternative regimens of prophylaxis are available for patients with documented intolerance to co-trimoxazole, but they are less effective, as has been shown for HIV-infected persons.2 In IBD patients the issue is to whom should PcP prophylaxis be given and for how long. At present, a top priority could be identifying risk factors for PcP in IBD patients treated with immunosuppressive drugs; this would allow physicians to make an individual risk assessment based on objective parameters in order to select patients for prophylactic treatment. In this sense, the authors cited1 suggest that it is reasonable to consider chemoprophylaxis for those patients with severe or fulminant disease, requiring corticosteroids and long-standing immunosuppressive or biological agents. Also, they think that other factors that might favor PcP prophylaxis include advanced patient age, medical comorbidities such as HIV infection, more extensive disease, and longer disease duration. However, the authors did not consider a major risk factor for PcP development, such as Pneumocystis colonization.3 The use of highly sensitive polymerase chain reaction (PCR) technologies has enabled detection of very low levels of Pneumocystis in respiratory samples from individuals without PcP. Many terms, including colonization, carriage, asymptomatic infection, and subclinical infection have been used to describe this situation.3 Studies have shown that individuals with underlying HIV infection or other causes of immunosuppression and those without immunosuppression but with chronic lung disease may often be colonized by P. jiroveci.3,4 Actually, there are no data about the risk of development of PcP in human colonized subjects who are treated with immunosuppressive therapies, although one study showed a PcP case out of 3 renal transplant recipients colonized by P. jiroveci after 6 weeks who underwent immunosuppressive therapy but without chemoprophylaxis for PcP.5 However, there is much information in animal models concerning the Pneumocystis colonization and PcP development after immunosuppression. The first models described in the study of PcP were rats. These animals are often colonized by Pneumocystis and “spontaneously” develop PcP after administration of corticosteroids for 6–14 weeks. In this way, other immunosuppressive therapies and animals may also be used to develop PcP.6 Individuals colonized with Pneumocystis may be at high risk of development of PcP when they have undergone immunosuppression. For this reason the identification of patients colonized by P. jiroveci before starting the immunosuppressive therapies could be a strategy for PcP prevention using chemoprophylaxis treatment. Oral washes have been confirmed to be a useful high specificity and sensitivity noninvasive procedure for the detection of Pneumocystis colonization through the use of molecular techniques that can be used in the general population.7,8 Thereby, detection of Pneumocystis colonization by PCR on oral washes and treatment with co-trimoxazol could be a practical strategy for PcP prevention in IBD patients undergoing immunosuppressive therapies. Effective and relatively safe prophylaxis is available. Rather than opting for PcP prophylaxis on the basis of features of disease or concurrent medications, we argue that the noninvasive diagnosis of Pneumocystis colonization by PCR on oral washes from IBD patients be used as a means of identifying individuals who are most likely to benefit from PcP prophylaxis. Further prospective trials are required to validate our proposed prevention strategy.