Effectiveness of the Quadrivalent HPV Vaccine in Preventing Anal ≥ HSILs in a Spanish Population of HIV+ MSM Aged > 26 Years.

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.

Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4 rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4 rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2 rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2 rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2 rs12137965G allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2 rs17013271T allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.

A rare case of bacteremia caused by Propionibacterium (Propionimicrobium) lymphophilum.

Propionibacterium (Propionimicrobium) lymphophilum is a Gram-positive anaerobic rod involved in few human diseases. We report a rare case of bacteremia due to this microorganism in an elderly patient. A 95-year-old woman without a remarkable medical history presented with dyspnea, chest pain and fever for seven days. Blood cultures resulted in isolation of P. lymphophilum. Resistance only to metronidazole was found. Treatment with amoxicillin-clavulanic acid was established, and the patient was discharged and improvement of her general condition was documented.

Comparative evaluation of two immunoassays for serological diagnosis of hepatitis E.

Serological testing for immunoglobulin M (IgM) antibodies to Hepatitis E virus (HEV) is useful for diagnosing acute hepatitis E. Our aim was to evaluate the performance of chemiluminescence immunoassay (HEV IgM; Vircell, Granada, Spain) in comparison with a manual enzyme immunoassay (Anti-HEV virus; Wantai, Beijing, China) for anti-HEV IgM detection. Seventeen HEV-RNA positive and 69 HEV-RNA negative sera were tested by both assays. Virclia sensitivity was 94.1%, whereas that of the enzyme immunosorbent assay (EIA) was 76.5%; specificity was 98.5% and 97.1% for Virclia and EIA, respectively. Differences between both assays were not statistically significant. Virclia HEV IgM showed excellent performance and can be a good alternative to conventional enzyme immunoassays for the detection of IgM against HEV.

Infections caused by Scedosporium/Lomentospora species: Clinical and microbiological findings in 21 cases.

The clinical and microbiological characteristics of infections caused by Scedosporium/ Lomentospora species in 21 patients are described. We searched retrospectively the records for Scedosporium/ Lomentospora species seen at the University Hospital Virgen de las Nieves from 2006 to 2017. Out of them, 16 were male; mean age at diagnosis was 57.8 (±SD 15) years; all patients had risk factors for fungal infection such as corticosteroids and/or immunosuppressive treatment in 18 (85.7%) patients, pulmonary diseases in seven (33.3%) cases, hematological malignancies in six (28.5%), and organ transplantation in three (14.2%) patients. Most patients had infection in the lung/pleura (17/80.9%); cough was present in 12 patients and dyspnea in another 12, and the mean interval until diagnosis was 13.6 days. The most frequent species was S. apiospermum/S. boydii in 14 patients (66.6%), followed by L. prolificans in seven. The diagnosis was obtained from sputum in 12 (57.1%) cases, followed by pleural fluid and bronchoalveolar lavage in two of each. The most frequently used antifungals were voriconazole and amphotericin B, but combination of more than one antifungal drug was only used in three patients. Ten patients were cured, and six patients died as a consequence of the infection; three patients had chronic infection. In general, infections caused by Scedosporium/Lomentospora species are rare, serious, and difficult to diagnose and treat, having a high index or mortality especially in those caused by L. prolificans.

Two Rare Cases of Wound Infections Caused by Trueperella bernardiae.

Trueperella bernardiae (T.bernardiae) is a gram-positive curved rod that is considered an uncommon pathogen involved in few infections. The true incidence of infections with this bacterium, and the clinical implications, remain unknown. We report 2 cases of wound infections in 2 patients who underwent different surgical procedures, although in the second case the microorganism was isolated in mixed culture. Culture of wound secretions resulted in isolation of T. bernardiae. Treatment was performed and resolution of the infections was documented.

Infected breast cyst due to Prevotella buccae resistant to metronidazole.

Prevotella buccae is a Gram-negative anaerobic rod involved in some human infections. We report the first case of an infected breast cyst in a non-puerperal women due to this pathogen. A 53-year-old woman presented with pain and a cystic lesion in the right breast. Culture of abscess drainage resulted in isolation of P. buccae. High level of resistance to metronidazole was documented. Treatment with drainage and amoxicillin-clavulanate was established, and improvement of this infection was observed.

Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM).

BACKGROUND: Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa. METHODS: This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1. RESULTS: Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96-0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17-1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001-1.811). CONCLUSIONS: This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor. CLINICAL TRIAL REGISTRATION: ISRCTN14732216 ( http://www.isrctn.com/ISRCTN14732216 ).

Candida Prosthetic Joint Infection. A Review of Treatment Methods.

Fungal microorganisms are still a rare cause of bone and joint infections. We report a new case of knee prosthetic joint infection due to Candida albicans in a patient with a previous two-stage right knee arthroplasty for septic arthritis due to S. epidermidis occurred several months ago. Moreover, the treatment in 76 cases of Candida prosthetic joint infection has been discussed. Forty patients were female and mean age at diagnosis was 65.7 (± SD 18) yrs. No risk factors for candidal infection were found in 25 patients. Infection site was the knee in 38 patients and hip in 36; pain was present in 44 patients and swelling in 24. The most frequent species was C. albicans, followed by C. parapsilosis. Eleven patients were only treated with antifungal drugs being the outcome favourable in all of them. Two-stage exchange arthroplasty was performed in 30 patients, and resection arthroplasty in other 30; in three patients one-stage exchange arthroplasty was done. A favourable outcome was found in 58 patients after antifungal plus surgical treatment, in 11 after antifungal treatment alone and in one after surgery alone. The type of treatment is still not clearly defined and an algorithm for treatment in fungal PJI should be established, but various types of surgical procedures may be applied.

Candida-induced prosthetic joint infection. A literature review including 72 cases and a case report.

BACKGROUND: The clinical and microbiological characteristics of prosthetic joint infection (PJI) caused by Candida species is described, including 72 cases in the literature and a case of Candida glabrata infection handled at the present centre. METHODS: We describe one patient and using the key words 'fungal prosthetic joint infection' and 'candida prosthetic joint infection' we searched MEDLINE (National Library of Medicine, Bethesda, MD), Web of Science, CINAHL and Cochrane systematic review databases for case reports of this condition. RESULTS: Out of the 73 patients, 38 were female; mean age at diagnosis was 65.7 (± SD 18) yrs; 50 had risk factors for candidal infection such as systemic disease (e.g. rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus) and/or immunosuppressive therapy in 18 (24.6%) cases, diabetes mellitus in 14 (19.1%), immunosuppression due to malignant or chronic disease in 24 (32.8%) and long-term antibiotic use in four (5.4%) patients. Infection site was the knee in 36 patients and hip in 35; pain was present in 43 patients and swelling in 23 and the mean surgery-diagnosis interval was 32 months. The most frequent species was C. albicans, followed by C. parapsilosis. The diagnosis was obtained from joint fluid aspirate in 33 cases and intra-operative samples in 16. Susceptibility to antifungals was tested in only 21 isolates. The most frequently used antifungals were fluconazole and amphotericin B. Two-stage exchange arthroplasty was performed in 30 patients and resection arthroplasty in 31; 56 patients were cured with a combination of medical and surgical treatment; one patient died from the infection. CONCLUSION: PJI caused by Candida requires a high index of suspicion; surgery with long-term antifungal therapy is recommended.

Localized mucosal leishmaniasis caused by Leishmania infantum mimicking cancer in the rhinolaryngeal region.

The clinical, microbiological, and histopathological findings of six patients with mucosal leishmaniasis are reported. Five of these patients were Spanish with no history of travel abroad, while the other was from Bolivia but had lived in Spain for more than 5 years. Two patients had no underlying disease, while the other four had several other medical conditions. Lesions were located in the nose in three patients and in the larynx in the other three. Symptoms included difficulty in swallowing, nasal obstruction, dysphonia, and polypoid lesions mimicking cancer. The diagnosis was based on the identification of parasites, or on PCR assay or culture. Five patients were treated with liposomal amphotericin B and the other with antimonial compounds.

Autochthonous lepromatous leprosy in a Spanish woman with burns on both feet and skin lesions.

The incidence of leprosy is decreasing worldwide and it is considered a rare disease in developed countries. In Spain, leprosy is mainly an imported disease with only few autochthonous cases seen. The diagnosis is difficult because of a low index of suspicion and the absence of visualisation of fast-acid bacilli in the lesions. Here, we report an autochthonous case of leprosy diagnosed after 4 years of evolution of skin lesions. Mechanical rupture of the biopsy helped finally to make the correct diagnosis of the disease.

Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study.

BACKGROUND: We conducted a retrospective analysis on the identification and antibiogram of all bacteria isolated from urine samples with microbiological confirmation of urinary tract infection (UTI) in a Spanish reference hospital over a 7-year period. METHODS: A retrospective analysis was performed of the identification and antibiogram data. RESULTS: A total of 31,758 uropathogens were isolated. Escherichia coli accounted for the majority (55.2%) of these, followed by Enterococcus faecalis (18.0%) and Klebsiella spp (10.3%). The highest E coli susceptibility rates were to imipenem (93.0%-99.8%), amikacin (97.3%-99.5%), nitrofurantoin (96.7%-98.9%), and fosfomycin (95.3%-100%), and the lowest were to cefuroxime (67.8%-86.4%), ciprofloxacin (61.2%-69.8%), and co-trimoxazole (55.0%-65.5%). We highlight the overall high activity of imipenem, piperacillin-tazobactam, nitrofurantoin, and fosfomycin on isolates versus the low activity of fluoroquinolones, co-trimoxazole, or cephalosporins. The activity of amoxicillin-clavulanic acid and fosfomycin decreased significantly over the 7-year study period. CONCLUSIONS: Imipenem and piperacillin-tazobactam appear to be good options for the empiric treatment of UTI acquired in hospital or requiring hospitalization, whereas nitrofurantoin and fosfomycin can be first-choice antibiotics for the treatment of uncomplicated community-acquired cystitis. However, surveillance studies are required to detect resistance to these antibiotics, given that an increase in uropathogen resistance rates may contraindicate its future use in empiric UTI therapy.

[Streptococcus agalactiae infective endocarditis]. / Endocarditis por Streptococcus agalactiae.

Streptococcus agalactiae infective endocarditis Streptococcus agalactiae is an unusual cause of infectious endocarditis. We describe the clinical characteristics, therapy and evolution of this infection in four patients diagnosed between 1996 and 2003. All four cases had native valve involvement and vegetations. All the patients had severe aortic failure and three of them also developed heart failure. Valve replacement surgery was performed in all four cases. Mortality was 50%. Infectious endocarditis due to S. agalactiae is very aggressive. Early surgery should be considered to prevent valve destruction and serious complications.

[Use of MPO chromogenic culture medium for routine processing of urine cultures]. / Utilidad del medio cromogénico MPO en el procesamiento habitual del urocultivo.

BACKGROUND: The chromogenic culture medium, MPO, was compared to culture on CLED (cystein, lactose, electrolyte-deficient) agar for the detection, enumeration and identification of urinary tract pathogens. METHODS: A total of 1,080 clinical urine specimens were assessed. All samples were inoculated in MPO and CLED using the calibrated loop method. RESULTS: Among 145 positive urine samples, 171 strains of bacteria were isolated (111 Escherichia coli, 26 Enterococcus spp., 12 Proteus spp., 10 Enterobacteriaceae from the Klebsiella-Enterobacter-Serratia group, 5 Pseudomonas aeruginosa, 4 Streptococcus agalactiae, 3 Staphylococcus spp. and 4 Candida albicans. For all samples, enumeration of microorganisms was comparable with the two media studied. Identification was also similar, except for 6 cases in which Enterococcus spp. were only detected with the chromogenic medium. CONCLUSIONS: Overall urine culture results with MPO chromogenic medium were similar to those obtained with CLED, making it a feasible alternative to the standard medium. Moreover, use of a chromogenic technique implies a significant reduction in workload, since additional tests to identify the microorganisms isolated are not needed in most cases.