The role of viral diagnostic tests in respiratory tract infections: moving forward.

The increased knowledge on virology and the increased potential of their diagnostic has risen several relevant question about the role of an early viral diagnosis and potential early treatment on the management of respiratory tract infections (RTI). In order to further understand the role of viral diagnostic tests in the management of RTI, a panel of experts was convened to discuss about their potential role, beyond what had been agreed in Influenza. The objective of this panel was to define the plausible role of aetiologic viral diagnostic into clinical management; make recommendations on the potential expanded use of such tests in the future and define some gaps in the management of RTI. Molecular Infection Viral Diagnostic (mIVD) tests should be used in all adult patients admitted to Hospital with RTI, and in paediatric patients requiring admission or who would be referred to another hospital for more specialised care. The increased use of mIVD will not only reduce the inappropriate use of antibiotics so reducing the antibiotic microbe resistance, but also will improve the outcome of the patient if an aetiologic viral therapy can be warranted, saving resource requirements and improving patient flows. Implementing IVD testing in RTI has various organizational benefits as well, but expanding its use into clinical settings would need a cost-effectiveness strategy and budget impact assessment.

[High-dose trivalent influenza vaccine: safety and immunogenicity]. / Vacuna antigripal trivalente de alta dosis: seguridad e inmunogenicidad.

Adults aged 65 years or older suffer the most severe health effects of seasonal flu. Although the influenza vaccine is effective in preventing influenza virus infection and its complications, it is not as effective in the elderly due to age-associated immunosenescence phenomenon. Since 2009, a high-dose trivalent influenza vaccine has been approved in the United States for the immunization of people ≥ 65 years with an antigen concentration four times higher than the standard vaccine. Multiple clinical trials carried out over different seasons, and using different methodologies, have shown that the high-dose trivalent influenza vaccine is not only more effective, but it also has a similar safety profile and is more immunogenic than the standard dose vaccine in the prevention of flu and its complications in the elderly. This document reviews the current scientific evidence on the safety and immunogenicity of high-dose influenza vaccine in people aged 65 years and over, and includes information from randomized clinical trials, observational studies with data from real clinical practice, and systematic reviews, and meta-analysis.

[High-dose trivalent influenza vaccine. Efficacy and effectiveness]. / Vacuna antigripal trivalente de alta dosis. Eficacia y efectividad.

Seasonal influenza is a major public health problem, particularly in older people. Influenza vaccine is the most effective way to prevent influenza virus infection and its complications, but due to immunosenescence, older people do not respond efficiently to immunization. In 2009, a high-dose trivalent influenza vaccine (IIV3-HD), containing four times more antigen than the standard-dose vaccine, was approved in the United States for the immunization of people aged 65 years and over. Numerous clinical trials, carried out at different seasons and using different methodologies, have shown that the IIV3-HD vaccine is, as well as safe, more immunogenic and more effective than the standard-dose vaccine in preventing influenza virus infection and its complications in older people. This paper reviews the available evidence on the efficacy and effectiveness of the IIV3-HD influenza vaccine in the elderly, with information from randomized clinical trials, as well as observational studies of real-world clinical practice and in systematic reviews/meta-analyses.

Viral Load in Spanish HIV patients: trends since the introduction of HAART.

The aim of this study is to describe trends in the percentage of samples with undetectable HIV viral load in Spain after the implementation of HAART. A descriptive observational study of HIV-VL measurements carried out in the microbiology department of the Hospital Clínico Universitario de Valladolid (HCUV) was conducted over a 9-year period (1996-2004). Regarding the trend over the study period, the 30-39 years age group accounted for most of the samples, although the percentage decreased from 65.5% to 59.6% over the study period. In contrast, the 40-49 years group increased from 9.1% to 14.5%. The preponderance of men, with percentages above 70%, was observed during the whole period. Although the purpose of this treatment is to maintain undetectable viral loads, since 1999 more than 60% of nonfirst samples had detectable levels. Based on the results of the VL trend among HIV/AIDS patients observed in this study, a large number of patients maintain elevated detectable VL years after HAART was implemented. Although different factors may be the cause of this and should be delimited in future studies, the phenomenon observed demonstrates the usefulness of monitoring VL and analyzing its time trend to gain further knowledge about the therapeutic results and care of HIV patients as a whole, also serving as the basis for corrective measures.

The situation of vaccines for the prevention of infections in adults: An opinion paper on the situation in Spain.

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table.

[Social and economic impact of chicken pox vaccine at 15 months of age. Castile and Leon, Spain, 2004]. / Impacto social y económico de la vacunación frente a la varicela a los 15 meses de edad en Castilla y León en 2004.

BACKGROUND: Chicken pox is a mainly childhood contagious disease caused by the Varicella Zoster Virus which gives rise to major healthcare and social costs. In 2005, Castile and Leon added chicken pox vaccine injections to its childhood vaccination schedule for eleven year-olds subject to coming down with this disease. This strategy does not modify the major mobility generated thereby at younger ages. This study is aimed at evaluating the profitability of systematic vaccination for chicken pox in infants 15 months of age in Castile and Leon. METHODS: An economic cost-benefit evaluation has been set out by jeans of a decision-making tree. A fictitious cohort of 100,000 children in Castile and Leon having reached 15 months of age in 2004 is studied, to whom the chicken pox vaccine would be administered in conjunction with the mumps, measles, rubella vaccines. This study is approached from the social standpoint. The time horizon selected was that of up until the study cohort was to reach 15 years of age, applying a 3% discount rate. A sensitivity analysis was made for evaluating the uncertainty of some variables... RESULTS: The cost-benefit ratio of adding this vaccine to the childhood vaccination schedule amounts to 1.23. CONCLUSIONS: From the social standpoint, administering chicken pox vaccine in conjunction with the mumps, measles, rubella vaccines show itself to be profitable. The profitability is modified both if a second dose of vaccine is added as well as if only the direct healthcare costs are analyzed.

[Description of Influenza B in seasonal epidemics in Spain]. / Descripción de la gripe B en las epidemias estacionales de España.

OBJECTIVE: Seasonal influenza epidemics are a major public health concern. They are caused by the influenza A and B viruses; although the A virus is more prominent, influenza B virus infection causes a disease with similar characteristics. There are two phylogenetically distinct influenza B lineages (B/Victoria and B/Yamagata), only one of which is present in the trivalent vaccine formulated each season. METHODS: Epidemiological data from the Spanish Influenza Surveillance System for 2007 to 2017 were reviewed to establish the relative proportion of each type of virus and the characterization of the B lineages in relation to the composition of the trivalent vaccine. RESULTS: The median proportion of B (2007-2017) was 27.2% (0.7%-74.8%) vs. 16.3% (0.4%-98.6%) for A-H3 and 44.2% (0.1%-98.0%) for pandemic A-H1N1 (20092017). The B lineages co-circulated in 8/10 seasons and there was mismatch with the B vaccine strain in 4/10 seasons. The B virus was dominant in 2007/08 and 2012/13 throughout Spain. There was a combination of dominance/codominance of influenza B and mismatch with the vaccine lineage in at least one third of epidemic seasons reviewed. CONCLUSIONS: Epidemiological information on influenza B has been less compiled in comparison with data on the A virus. Influenza virus type B is responsible for a significant number of cases in almost all seasons. The predominant B lineage in each season is unpredictable, affecting the protection conferred by the seasonal vaccine. Spanish epidemiological data support the rationale for a quadrivalent vaccine with both B virus lineages similarly to data from other settings.

[Epidemiological study of Staphylococcus aureus nasal carriage in senior centers]. / Estudio epidemiológico de portadores nasales de Staphylococcus aureus en centros de mayores.

The observation of an increasing number of methicillin-resistant Staphylococcus aureus (MRSA) isolates in some population groups prompted us to study the risk factors and the epidemiological profile of S. aureus nasal carriage in healthy adults 65 years of age and older residing in the province of Segovia. Attention was particularly focused on the possibility that some of the infections were community-acquired. We conducted a prospective and observational study of people who usually visited senior citizen centers in the province of Segovia (Carbonero, Cuéllar, Cantalejo) and its capital. The analysis period took place between January and May 2003. Infections were classified as community-acquired, hospital-acquired or health-care associated. Isolates of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) were studied by pulsed-field gel electrophoresis (PFGE). There were 34 (19.5%) The prevalence of nasal carriage of S. aureus was 19.5% and that for MRSA was 1.1%. Female sex was significantly associated with the carriage state. All S. aureus isolates were mupirocin-susceptible. 100% susceptibility and specificity was obtained through latex agglutination testing. The molecular study showed that the transmission for MRSA was monoclonal and that for MSSA was more policlonal. The results presented here form the basis for similar studies in other Spanish senior citizen centers and provide evidence that MRSA strains are beginning to circulate and are becoming significantly established within the community, thus highlighting the need for implementing control strategies to prevent dissemination.

[Prevalence of human papillomavirus in Spanish women from a population screening program]. / Prevalencia de virus del papiloma humano en mujeres españolas de un programa de cribado poblacionales de riesgo.

OBJECTIVE: The human papillomavirus (HPV), is necessary to cause a woman developing cervical cancer. The aim of the study was to estimate the prevalence of women with HPV infection, covered by the program of prevention and early detection of cervical cancer of Castile and León (Spain). METHODS: Samples of women included in the screening program were analyzed. Including a total of 120,326 cervical swab samples, collected in the period from January 2012 to December 2014. RESULTS: 12,183 HPV positive samples were detected, representing a prevalence of 9.6 ‰, (IC 95% 9.5%-9.8%) in the female population. High-risk HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence correlates inversely with women age. Coinfections of multiple genotypes were found in one third of screened women population. CONCLUSIONS: Data showed in this study are the first and wider Spanish results from a cervical cancer screening program population non opportunistic based on HPV detection. These results would serve as a reference for future prevalence studies and to evaluate the future impact of HPV vaccination campaigns.

Factors associated with the evolution of the viral load in individuals with HIV infection.

The temporal evolution of the viral load (VL) in a group of patients under clinical care and the identification of individual variables that determined this evolution was studied using a retrospective descriptive study of the VL determinations on 1336 patients between September 1996 and June 2000. During follow-up, patients' VLs increasingly fell below the detection threshold. Those patients who had received antiretroviral treatment prior to the monitoring of the viraemia presented lower VLs at the start of their follow-up. Those patients who had been cared for on the same unit throughout their follow-up maintained lower VLs. Female patients uniformly presented lower VL results than the males. The immunological status at the beginning of follow-up and the basal VL determined the initial evolution of the patients' VL, although it did not do so in the final stages of follow-up. The immunological and virological state at the onset of the follow-up determines the evolution of the patients' VL.

Efficacy of two modalities of triple HIV therapy: probable superiority of indinavir.

The introduction of the so-called highly active antiretroviral therapies has had an impact on the natural history of the HIV infection. The aim of this contribution is to assess the differences in terms of plasma viral load (VL), as a reflection of therapy success or failure. A retrospective study was made of the changes in VL in two cohorts of patients depending on the drugs included in the triple therapy prescribed to them. The comparison of the triple therapies containing any reverse transcriptase inhibitor and different protease inhibitors, indinavir (IDV) (239 patients) versus saquinavir (SQV) or ritonavir (RTV) (138 subjects), showed a significantly higher percentage of patients reaching a 'non-detectable' VL among those receiving indinavir (67.8% versus 54.3%; P = 0.011). The interval before VL levels rose above 30,000 RNA copies/ml was different in the two groups: 385 days (276-495 days) for therapies including indinavir, and 239 days (86-391 days) for saquinavir or ritonavir. This seems to support the excellent behaviour of indinavir when its efficiency is compared with other protease inhibitors acting as potential competitors.

[Antiretroviral therapy from 1996-2000]. / Tratamiento antirretroviral en el periodo 1996-2000.

A retrospective study was carried out from September 1996 to June 2000 and examined the antiretroviral therapies prescribed to HIV patients in whom the viral load had been determined. Triple therapy was the most frequently prescribed during the study and the annual percentage increased to 60% in the last semesters analyzed. Large variability in antiretroviral combinations was observed and depended on the clinical center and unit. The number of individuals who began viral-load monitoring before being treated with antiretroviral drugs showed a progressive increase.

Prevalence of genotypic resistance in untreated HIV-infected patients.

The aims of this retrospective study are to assess the prevalence of primary resistances to antiretroviral drugs, both reverse transcriptase and protease inhibitors in untreated patients from Spain, and to determine their possible association with several epidemiological variables. A total of 148 samples belonging to 145 patients were processed using the genotypic technique VERSANT HIV 1 (LiPA) in order to study the presence of mutations at codons 41, 69, 70, 74, 75, 103, 106, 151, 181, 184 and 215 of the reverse transcriptase gene (VERSANT HIV 1 RT) and at codons 30, 46, 48, 50, 54, 82, 84 and 90 of the protease gene (VERSANT HIV 1 Protease). The patients' epidemiological variables which could be relevant to HIV infection were also analyzed. The successful amplification rate was 77.70% for LiPA RT and 91.21% for LiPA P. In the case of LiPA RT, statistical significance (p < 0.05) was observed when successful amplification was related to viral load level (p < 0.001). Global prevalence of resistance was 20.27%. Mutations in the reverse transcriptase gene were found in eight samples (5.40%). Using LiPA P, mutations were detected in 16.21% of cases, with V82A being the most frequently detected mutation (15/24, 62.50%) in nine samples. The V82A mutation was found alone (66.6%) and it was found together with the I84V mutation in five samples (20.83%). I84V was the second most frequently detected mutation (13/24, 54.16%). No statistical significance was found for any of the epidemiological variables. Due to the problems encountered in a high percentage of samples, the authors concluded that the amplification technique should be improved. The prevalence of resistance detected was around the mean of that found by other authors.

[Inflammation and infection in stable coronary disease and acute coronary syndrome]. / Inflamación e infección en la enfermedad coronaria estable y en el síndrome coronario agudo.

OBJECTIVE: To study whether inflammation and infection are related to coronary artery disease. DESIGN: Sixty patients (44 males, mean age 62 +/- 13 years) with acute coronary syndrome and 40 with stable coronary artery disease (31 males, age 64 +/- 10 years) and a control group of 40 individuals (34 males, 53 +/- 5 years) were analyzed. IgG against Chlamydia pneumoniae, Cytomegalovirus and Helicobacter pylori plus C-reactive protein were assessed in all serum samples. In addition, IgM against C. pneumoniae and Cytomegalovirus on admission and C-reactive protein one month later were measured in acute patients. RESULTS: No IgM seropositivity was observed. A high prevalence of IgG seropositivity with no significant differences among the groups was found: C. pneumoniae: acute group 44 (73%), stable group 29 (73%) and control group 25 (63%); Cytomegalovirus: 55 (92%), 37 (92%) and 38 (95%), respectively; and H. pylori, 43 (72%), 32 (80%) and 34 (85%) respectively. There was a high rate of positive C-reactive protein in the acute group: 48 (80%) vs 10 (25%) the stable group and 0% the control group (p < 0.001). C-reactive protein levels were higher in Q-wave infarction than in unstable angina/ non-Q-wave infarction (median 22.65 vs 7.69, p < 0.001). One month later, C-reactive protein levels decreased (median 22.65 vs 3.38, p < 0.001), but were still positive in 40%. CONCLUSIONS: These data suggest that inflammation is detected by the commonly used methods in clinic practice in acute coronary syndromes and to a lesser extent in stable coronary artery disease. It seems that different mechanisms other than infection account for this inflammatory response, at least this being so when infection is assessed by serology. Serology does not appear to be an adequate method to determine the possible relationship among coronary syndromes, infection and inflammation.

[Evaluation of various criteria for the interpretation of western blot for the diagnosis of human immunodeficiency virus infection. Spanish Group for the Study of HIV-2]. / Evaluación de diferentes criterios de interpretación del Western blot para el diagnóstico de la infección por el virus de la inmunodeficiencia humana. Grupo Español para el Estudio del VIH-2.

BACKGROUND: The Western blot (WB) is the most commonly used test to confirm the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Different criteria of interpretation of the band profile have been proposed with there being no unanimity as to its reliability. The sensitivity and specificity of several criteria proposed for the interpretation of WB were evaluated and the individual significance of the reactivity of each band of the WB was analyzed. METHODS: The presence of antibodies against HIV-1 was prospectively studied in 8,073 samples of subjects with risk of infection. A total of 1,993 (25%) were reactive by ELISA and 1,261 were analyzed by WB, with a semiquantitative reading of the bands with a point scale from 0 to 2 being performed. The final interpretation of the WB (negative, doubtful, or positive) was carried out following 5 recommendations of usage. A test designed with synthetic peptides (Pepti-lav) was used as a reference and in discordant cases, other more specific serologic tests and/or genetic analysis by polymerase chain reaction (PCR) were performed. RESULTS: In order of frequency, the greater sensitivity was found to be for the CRSS (Consortium for Retrovirus Serology Standardization) criteria (97.9%), OMS (96.6%), CDC (Center for Disease Control) (95.9%), ARC (American Red Cross) (95.6%) and FDA (99.8%). The greatest specificity was for the criteria of the OMS, and FDA (99.8%). In order of frequency, the most frequent bands in HIV-1 + individuals were gp160 (99%), gp120, p24, p31, p55, p68, gp41, and p17 (68%). In non infected individuals, the recognized bands were, in decreasing order, p24, p17, p55, p68, p31, and glucoproteins. CONCLUSIONS: Different criteria of interpretation of the Western blot provide different degrees of sensitivity and specificity. The Western blot is a non standardized, expensive, laborious technique of subjective interpretation which provides an appreciable number of undetermined results.

[A multicenter study of infection with human immunodeficiency virus type-2 (HIV-2) in Spain (1991). The Spanish Group for the Study of HIV-2]. / Estudio multicéntrico de la infección por el virus de la inmunodeficiencia humana tipo 2 (VIH-2) en España (1991). Grupo Español para el Estudio del VIH-2.

BACKGROUND: To January 1991 thirteen cases of HIV-2 infection had been reported in Spain. Paradoxically, neighboring countries, i.e. France and Portugal, have reported more than one thousand cases, and are the most HIV-2 prevalent areas outside West Africa. We report the results of a prospective, nationwide study on the prevalence of HIV-2 infection conducted in Spain in 1991. In addition, an evaluation of testing methodologies is made. METHODS: Sera collected from 8,073 individuals at high-risk for HIV infection were screened by a combined HIV-1 plus HIV-2 ELISA. Reactive samples were further evaluated by three tests, as HIV-1 Western blot (WB), HIV-2 specific WB, and a synthetic peptide assay immuno-dot (Pepti-lav, Pasteur). RESULTS: Fifteen (0.18%) individuals met criteria of HIV-2 infection in both specific WB and SPA. Four (27%) of them showed reactivity to both HIV-1 and HIV-2, and the dual infection was confirmed by polymerase chain reaction (PCR) in 2 out of 3 available samples. The SPA showed higher sensitivity and specificity than WB in the diagnosis and distinction of HIV-1 and HIV-2 infections. CONCLUSIONS: To January 1992, 28 cases of HIV-2 infection have been described in Spain. All but two were African immigrants. The first cases of HIV-1 plus HIV-2 coinfection have been identified. In HIV high-risk populations, SPA may provide an excellent alternative to WB to confirm ELISA reactive samples.

[Previous dissociative psychiatric disorder and status epilepticus in a case of acute HIV infection]. / Trastorno disociativo psiquiátrico previo y status epiléptico en un caso de infección aguda por VIH.

We described an 18 old homosexual man who after 5 days developed a neurologic picture associated with Human Immunodeficiency Viruses (HIV) seroconversion. The patient had developed a dissociative psychiatric disorder 6 months before, and after resolution of the acute neurologic disease a mild neuro-psychiatric disorder remained. After mononucleosis-like syndrome of three weeks, the patient developed a meningo-encephalitic process 48 h post admission. He evolved with tonic seizures and twilight state and was admitted into Intensive Care Unit because of epileptic status and deep coma. Evolution was favourable after 72 h of treatment with acyclovir and antiepileptic drugs. Laboratory data showed an inverted T4/T8 ratio and seroconversion to HIV-antibodies and p24-antigen both in serum and CSF. These observations confirm the existence of psychiatric as well neurological alterations in acute HIV infection, and also the significance of p24-antigen and Western-Blot in serum and CSF in showing the seroconversion profile.

[Observational study on the efficacy of the application of two classical regimens of triple antiretroviral therapy]. / Estudio de campo sobre la eficacia de la aplicación de dos modalidades clásicas de triple terapia antirretroviral.

BACKGROUND: To compare the temporal evolution of viral load and CD4 parameters in two cohorts of HIV infected patients enrolled in classical triple antiretroviral regimens. METHODS: Retrospective, observational, descriptive study of the proportions of patients reaching undetectable levels of viral load (VL) as well as the time necessary to get it. The two cohorts were as follows: 91 HIV patients on triple therapy with zidovudine plus lamivudine and indinavir (cohort A) versus 80 HIV patients with Stavudine plus Didanosine and Indinavir (cohort B). RESULTS: The evolution of the patients in terms of percentages who reach undetectable VL was similar in the two therapeutic cohorts (75.8%for cohort A vs 73.8% for cohort B) along the duration of the study (four years). However, the mean time period needed to reach undetectable VL was different, 209 days (IC 95% 175-243 days) for patients in zidovudine plus lamivudine and indinavir and 330 days (IC 95% 263-396 days) for stavudine plus didanosine and indinavir regimen. The immunological status observed in the patients when reaching his first undetectable VL was significantly different. The proportion of patients with CD4 cells counts >200/mm3 in cohort A was 83.1% while for patients from cohort B was 65.4% (p=0.032). CONCLUSIONS: This observational study from clinical settings seems demonstrate similar efficacy to reach undetectable VL with both classical triple antiretroviral therapies evaluated but a shorter delay of time to reach that virological situation for zidovudine plus lamivudine and indinavir regimen is reported.