Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

OBJECTIVES: We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS: SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. RESULTS: Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm3 (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. CONCLUSIONS: The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.

Effectiveness of 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and over in the Region of Madrid, Spain, 2008-2011.

Invasive pneumococcal disease (IPD) is a notifiable disease in the Region of Madrid. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for children and adults aged two years or over with a high risk of disease, and for all adults aged 60 and over. We describe the evolution of IPD incidence from 2008 to 2011 in people aged 60 years and over and PPV23 vaccine effectiveness (VE). VE is estimated using both the screening method and indirect cohort method. The incidence of IPD varied from 20.0 in 2008 to 15.2 per 100,000 inhabitants in 2011 (RR: 0.8; 95% CI: 0.6­0.9). Adjusted VE estimated with the screening method was 68.2% (95% CI: 56.2­76.9). VE with the Broome method was 44.5% (95% CI: 23.8­59.6) for all PPV23 serotypes, and 64.4% (95% CI: 45.2­76.8) for PPV23 serotypes not included in conjugate vaccines. VE was lower in patients aged 80 years and older (25.5%; 95% CI:-23.2 to 55.0) and those with highrisk medical conditions (31.7%; 95% CI: -2.2 to -54.4). Adjusted VE was 44.5% (95% CI: 19.4-61.8) within 5 years of vaccination and 32.5% (95% CI: -5.6 to 56.9) after 5 years. These results are compatible with current recommendations for PPV23.

Risk factors and clinical significance of invasive infections caused by levofloxacin-resistant Streptococcus pneumoniae.

PURPOSE: Fluoroquinolones are recommended for the treatment of pneumonia. The recognition of risk factors for invasive levofloxacin-resistant Streptococcus pneumoniae is important for the design of treatment. METHODS: A retrospective review of cases of invasive pneumococcal infections in adults was undertaken. Epidemiologic data, predisposing factors, clinical variables, and outcome were recorded from previously established protocols. Antimicrobial susceptibility was determined by disk diffusion and the Etest method. Serotyping was performed by latex agglutination and Quellung reaction. RESULTS: Twenty patients with infection caused by levofloxacin-resistant pneumococci [minimum inhibitory concentration (MIC) ≥2 µg/ml] were compared with 102 patients harboring levofloxacin-susceptible strains; 80% of levofloxacin-resistant pneumococci were resistant to ≥3 antibiotics but susceptible to penicillin. Most levofloxacin-resistant strains (80%) belonged to serotype 8. In comparison, only 8% of levofloxacin-susceptible pneumococci belonged to serotype 8. In the multivariate analysis, residence in public shelters [odds ratio (OR) 26.13; p 0.002], previous hospitalization (OR 61.77; p < 0.001), human immunodeficiency virus (HIV) infection (OR 28.14; p = 0.009), and heavy smoking (OR 14.41; p = 0.016) were associated with an increased risk of infection by levofloxacin-resistant pneumococci. Mortality caused by levofloxacin-resistant and levofloxacin-susceptible pneumococci was 35 and 14%, respectively. Among HIV-positive individuals infected with levofloxacin-resistant pneumococci 44% died, but only 12.5% of HIV-positive patients with levofloxacin-susceptible strains died. CONCLUSIONS: We observed the emergence of serotype 8 as the main cause of invasive disease caused by levofloxacin-resistant S. pneumoniae. HIV-positive patients seem to be prone to infection caused by multidrug-resistant serotype 8 and have a high mortality rate.

[Evolution of the serotypes causing invasive pneumococcal disease along 2008-2022 in a Level 2 Public Hospital of the Madrid Region, in relation to their inclusion in different conjugate vaccines]. / Evolución de los serotipos causantes de enfermedad neumocócica invasiva aislados durante 2008-2022 en un Hospital Público Madrileño de nivel dos, en relación con su inclusión en diferentes vacunas conjugadas.

OBJECTIVE: The use of conjugate vaccines against Streptococcus pneumoniae originates changes in the invasive pneumococcal disease (IPD). The aim of this study was to in vestigate the evolution of S. pneumoniae serotypes isolated in the Hospital Universitario de Getafe between 2008 and 2022. METHODS: 313 of S. pneumoniae strains were studied. Serotyping was carried out by latex agglutination (Pneumotest-latex) and the Quellung reaction. In addition, the minimal inhibitory concentration (MIC) was determined against penicillin, erythromycin and levofloxacin by the concentration gradient method (E-test) according the EUCAST breakpoints. RESULTS: The most frequent serotypes throughout the study period were 8, 3, 19A, 1, 11A and 22F corresponding to 46.6% of the isolates. Along 2008-2012 the serotypes 3, 1, 19A, 7F, 6C and 11A represented altogether 53.6% of the isolates. Between 2013 and 2017 the serotypes 3, 8, 12F, 19A, 22F and 19F grouped 51% of the isolates. During 2018-2022 the serotypes 8, 3, 11A, 15A, 4 and 6C included the 55.5% of the cases. In total 5 strains (1.6%) were penicillin resistant, 64 (20.4%) erythromycin resistant and 11 (3.5%) levofloxacin resistant. The MIC50 and MIC90 levels maintained stables along the time. CONCLUSIONS: The conjugate vaccines use with different serotype coverage conditioned a decrease of the vaccine-included and an increase of non-covered. Despite these changes, the global antimicrobial susceptibility patterns to erythromycin and levofloxacin maintained relatively stables. The resistance a penicillin was low, not finding this type of resistant strains in the last study period.

[SARS-CoV-2 variants, a still unfinished story]. / Variantes de SARS-CoV-2, una historia todavía inacabada.

Mutations in the SARS-CoV-2 genome can affect the gene encoding the Spike (S) antigen, which interacts with the host cell specific receptor, selecting mutant variants with changes in their infective capacity, pathogenic potential and resistance to neutralizing antibodies. The nomenclature to design the variants uses a colloquial form referred to the country or place of detection, a code from the "Pangolin" database and one from the "Nextstrain" page. New variants that have spread include the British B.1.1.7 (20I/501Y.V1), the South African B.1.351 (20H/501.V2), the Brazilian P.1 (20J/501Y.V3), the Californians B.1.427 B.1.429 (20C/S:452R) and the most recent, the Indian B.1.617 (VUI-21APR-01).The gold standard for the identification of the variants is whole genome sequencing. However, real-time PCR techniques have already been developed for the detection of specific mutations that can facilitate their presumptive identification.The impact of these variants on global vaccination programs has raised concern. It is generally thought that, since the response evoked by the vaccine against the S antigen is directed at the entire protein and the mutations only affect specific regions, the escape effect of the vaccine antibodies will be limited. Among the future strategies proposed for immuno-protection, the increase in the number of doses, the alternation of vaccines and the development of specific vaccines against different variants has been suggested.

Approach to COVID-19 pandemic management in Madrid. Chronic of a year.

After more than a year of pandemic, the international medical community has changed the perception of fear to one of respect for SARS-COV-2. This has been the consequence of the integral study of all the dimensions of the disease, from viral recombinant capacity to transmissibility, diagnosis, care and prevention. This document summarizes the main strategic lines of study and approach to the pandemic in Madrid.

Community-wide measles outbreak in the Region of Madrid, Spain, 10 years after the implementation of the Elimination Plan, 2011-2012.

We describe a community-wide outbreak of measles due to a D4 genotype virus that took place in the Region of Madrid, Spain, between February 2011 and August 2012, along with the control measures adopted. The following variables were collected: date of birth, sex, symptoms, complications, hospital admission, laboratory test results, link with another cases, home address, places of work or study, travel during the incubation period, ethnic group, and Mumps-Measles-Rubella (MMR) vaccination status. Incidences were calculated by 100,000 inhabitants. A total of 789 cases were identified. Of all cases, 36.0% belonged to Roma community, among which 68.7% were 16 months to 19 y old. Non-Roma cases were predominantly patients from 6 to 15 months (28.1%) and 20 to 39 y (52.3%). Most cases were unvaccinated. We found out that 3.0% of cases were healthcare workers. The first vaccination dose was brought forward to 12 months, active recruitment of unvaccinated children from 12 months to 4 y of age was performed and the vaccination of healthcare workers and of members of the Roma community was reinforced. High vaccination coverage must be reached with 2 doses of MMR vaccine, aimed at specific groups, such as young adults, Roma population and healthcare workers.

Seroprevalence of measles and rubella virus antibodies in the population of the Community of Madrid, 2008-2009.

The seroprevalence (SP) of measles and rubella virus antibodies is presented by age groups obtained in the IV Serosurvey of the Region of Madrid (2008-2009). The target population is composed of residents with ages ranging between 2 and 60 years in the Region of Madrid. A two-stage cluster sample is used. The SP of measles virus antibodies is 97.8% (CI 95%: 97.3-98.2). The highest SP is observed in the 2-5 year and 41-60 year age groups. The point estimate does not reach 95% in the 16-20 and 21-30 year age groups. The SP of rubella virus antibodies is 97.2% (CI 95%: 96.5-97.7). The SP is over 95% in all of the age groups. In immigrant women between the ages of 16 and 49, the SP is 95.9% (CI 95%: 93.7-97.4). The identification of groups susceptible to the measles virus in young adults could lead to outbreaks as a result of importing the virus. The circulation of the rubella virus is possible among immigrant women aged between 16 and 49 years, which could lead to the appearance of SRC cases. Epidemiological surveillance will allow the impact on the measles and rubella elimination plan to be determined in the future.

Q fever in pregnancy: case report after a 2-year follow-up.

We report an acute Q fever case, a febrile syndrome, in the 14th week of pregnancy. Placental infection was documented by Coxiella burnetii culture. Newborn infection was ruled out on the basis of the absence of serological evidence after 2 years and on clinical normality. Serological diagnosis is reviewed here, as maternal serology was suggestive of chronic Q fever. The clinical progress, following extended observation, was consistent with acute infection. A QpDV plasmid, already described as being common to acute and chronic European cases, was detected.

[Cytomegalovirus seroepidemiology in the community of Madrid]. / Seroepidemiología frente a citomegalovirus en la Comunidad de Madrid.

BACKGROUND: Cytomegalovirus (CMV) is frequently asymptomatic. However, it constitutes an important cause of congenital disease and severe pathology in immunodepressed patients, thus representing an important problem in Public Health. The object of this work was to study the prevalence of IgG against CMV (IgG-CMV) in the general population from Madrid. METHODS: It is a transversal study, in which IgG-CMV was assayed in a representative sample of the general population from the Region of Madrid, aged 2 to 60 years (n = 2030). Participants were recruited by a two-stage cluster sample procedure from those attending primary health care centres between October, 1993 and February, 1994. For the statistical analysis the chi 2 and chi 2 lineal trend tests were employed. The percentages of seroprevalence and the specific odds ratios were calculated with confidence intervals of 95%. RESULTS: The overall seroprevalence has been 62.8% (IC95% 60.6-64.9), ranging from 58.4% (IC95% 55.2-61.5) in men to 66.7% (IC95% 63.7-69.5) in women. A significant association between increase of the age and increment of the seroprevalence was observed. The consult to dentistry, the antecedent of surgery, as well as tattooing and acupuncture has been identified as risk factors of acquiring the infection. On the other hand, to have carried out University studies seems to act as a significant factor of protection. CONCLUSIONS: Although the risk factors detected indicates a transmission by blood, the high prevalence suggests the existence of other more common ways. The age-dependent seroprevalence increase confirms an important number of infections in the adult age. However, it cannot be exclude that this increase responds to an effect cohort due to socio-economic improvements similar to the detected for other virus.

[Effectiveness and duration of the immunity of the vaccine against serogroup A+C meningococcus]. / Efectividad y duración de la inmunidad de la vacuna frente al meningococo serogrupo A y C.

BACKGROUND: In 1995 the Community of Madrid detected an increase in the number of cases of meningococcal disease caused by serogroup C. In 1997 a mass vaccination campaign was carried out in relation to the population between 18 months and 19 years of age. The purpose of this study is to ascertain the immune response produced by the vaccine and its relationship to the age of the subjects. METHODS: A sample group of 1,003 children vaccinated during the campaign was selected. A blood sample was extracted prior to vaccination and after one, six (only a under 5 years old) and twelve months had transpired. In order to assess the immune response, the levels of bactericidal and total antibodies were measured. RESULTS: The prevalence of seroconversion measured by bactericidal antibodies is 89.6%. The response is low in children under 3 (34.8%), increases with age and, from 7 years on, surpasses the 90% mark. After 6 months, the prevalence of protective levels in children under 5 years of age drops noticeably (31.3%). After one year, the prevalence drops significantly, particularly in children under 7 years of age. The proportion of individuals with total antibody response after one month is over 90%, and remains high after one year in all of the age groups (97.5%). CONCLUSIONS: The response measured by means of total antibodies contradicts the clinical response to the vaccination and the measurement by means of bactericidal antibodies underestimates the protection if it is compared with the results of vaccinal efficacy, for which reason, we need to search for biological indicators that would correlate adequately with the clinical response following immunisation.

[Eosinophilic fasciitis: its relationship with L-tryptophan ingestion]. / Fascitis eosinofílica: relación con la ingesta de L-triptófano.

The tryptophan ingestion has recently been involved in the etiology of the eosinophilia-myalgia syndrome. The common findings shared by eosinophilic fasciitis (EF) and that syndrome has suggested a possible role of tryptophan consumption in the development of both diseases. We report two cases of EF whose onset was likely attributed to tryptophan ingestion. Healing was achieved in both patients: the first one had a spontaneous remission and the second patient received glucocorticoid treatment. The EF pathogenesis is yet unknown as the tryptophan role involved in its development. It is likely that tryptophan could release some metabolic factor that support the patient propensity to this illness. It is remarkable to search for the possible tryptophan ingestion in every patient who presents a sclerodermiform syndrome, particularly in EF patients.

[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection]. / Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes naive con infección por VIH avanzada.

BACKGROUND: Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive. PATIENTS AND METHODS: Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks. RESULTS: A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients. CONCLUSIONS: In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.