Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults.

Hospital-acquired pneumonia (HAP) is often more severe and life-threatening than community-acquired pneumonia (CAP). The role of Streptococcus pneumoniae in CAP is well-understood, but its role in HAP is unclear. The objective of this study was to summarize the available literature on the prevalence of S. pneumoniae in HAP episodes. We searched MEDLINE for peer-reviewed articles on the microbiology of HAP in individuals aged ≥18 years, published between 2008 and 2018. We calculated pooled estimates of the prevalence of S. pneumoniae in episodes of HAP using a random-effects, inverse-variance-weighted meta-analysis. Forty-seven of 1908 articles met the inclusion criteria. Bacterial specimen isolation techniques for microbiologically defined HAP episodes included bronchoalveolar lavage, protective specimen brush, tracheobronchial aspirate and sputum, as well as blood culture. Culture was performed in all studies; five studies also used urine antigen detection (5/47; 10.6%). S. pneumoniae was identified in 5.1% (95% confidence interval (CI): 3.8-6.6%) of microbiologically defined HAP episodes (N = 20), with 5.4% (95% CI: 4.3-6.7%, N = 29) in ventilator-associated HAP and 6.0% (95% CI: 4.1-8.8%, N = 6) in non-ventilator-associated HAP. S. pneumoniae was identified in 5.3% (95% CI: 4.5-6.3%) of HAP occurring in the intensive care unit (ICU, N = 41) and in 5.6% (95% CI: 3.3-9.5%, N = 5) outside the ICU. A higher proportion of early-onset HAP (10.3%; 95% CI: 8.3-12.8%, N = 16) identified S. pneumoniae as compared with late-onset HAP (3.3%; 95% CI: 2.5-4.4%, N = 16). In conclusion, S. pneumoniae was identified by culture in 5.1% of microbiologically defined HAP episodes. The importance of HAP as part of the disease burden caused by S. pneumoniae merits further research.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology.

This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990-2012. PubMed and EMBASE were searched using the terms "empyema", "complicated pneumonia", "pleural infection", "necrotizing pneumonia", "pleural effusion", "parapneumonic effusion", "pneumatocele", or "lung abscess"; "pneumococcal" or "Streptococcus pneumoniae"; and "serotype" for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013. Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children. The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990-2012; specific increases varied by geographic region. The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates. The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine.

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

Burden of paediatric invasive pneumococcal disease in Europe, 2005.

Within the European Union (EU), documenting the burden of invasive pneumococcal disease (IPD) in infants and children is important for coordinating effective pneumococcal immunization policies. Our objective was to document the burden of IPD in countries of the EU plus Switzerland and Norway. European affiliates of Wyeth Vaccines made available recent epidemiological data on IPD from local disease surveillance programmes, including unpublished sources. Recent literature and websites were also searched to provide as wide a representation as possible. This included OVID and abstracts from a number of international meetings, dating from the year 2000. The reported rates of paediatric IPD per 100000 (age) ranged from a low of 1.7 (<2 years) to 4.2 (2-15 years) in Sweden to a high of 93.5 to 174 (<2 years) to 56.2 (<5 years) in Spain. The percentage of circulating serotypes causing IPD that are covered by 7-valent pneumococcal conjugate vaccine (PCV) IPD serotype coverage ranged from 60% to 80% for European children aged <2 years. Under reporting, differences in reporting methods, antibiotic prescribing and disparities in blood-culturing practices may explain the differences in reported disease incidence. Because of the excellent clinical efficacy of the PCV against IPD, national pneumococcal vaccination programmes in Europe have the potential to prevent much morbidity and mortality.

Controlling invasive pneumococcal disease: is vaccination of at-risk groups sufficient?

Risk factors for invasive pneumococcal disease (IPD) include young and old age, comorbidities (such as splenic dysfunction, immunodeficiencies, chronic renal disease, chronic heart or lung disease or cerebral spinal fluid leak), crowded environments or poor socioeconomic conditions. Universal use of the 7-valent pneumococcal conjugate (7vPncCRM) vaccine for infants and young children has led to significant decreases in IPD in the vaccinated population (direct protection), and there has also been a decrease in the incidence of IPD among the nonvaccinated population (indirect immunity; herd protection). While 7vPncCRM vaccine is administered universally to children in USA, many countries of the European Union have chosen to target children with comorbidities. This review aims to highlight individual risk factors for IPD, describe studies that evaluated pneumococcal conjugate vaccines in at-risk groups and estimate the proportion of at-risk children who may have been vaccinated in the European Union since the 7vPncCRM vaccine was introduced, using UK as an example. Although immunisation targeting only children with comorbidities may achieve satisfactory results for a few, many otherwise healthy children at risk simply because of their age will be neglected, and herd protection might not be established.

Chronic fatigue syndrome is associated with diminished intracellular perforin.

Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described. Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls. A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.

Relative preservation of natural killer cell cytotoxicity and number in healthy AIDS patients with low CD4 cell counts.

OBJECTIVE: This study examines whether there may be an immune component that protects a relatively rare group of HIV-infected people with very low CD4 cell counts (< or = 50 x 10(6)/l) who have prolonged asymptomatic periods. DESIGN/METHODS: Three groups were recruited in Miami: (i) healthy low CD4 cell count patients (HLC; n = 30) who, for 9 months had < 50 x 10(6) CD4 cells/l, were asymptomatic and were not on protease inhibitors during that time; (ii) HIV comparison group (Comp; n = 60) who had CD4 cell counts predominantly 150 x 10(6) to 400 x 10(6)/l and never had AIDS Category C symptoms; this group was also followed for CD4 cell count and viral load change over 6 months; and (iii) healthy community controls (n = 33). The study was replicated at the University of California at Los Angeles (UCLA) with HLC (n = 31) versus HIV-negative laboratory controls (n = 28). RESULTS: The HLC patients were significantly higher than the Comp group on natural killer cell cytotoxicity (NKCC) and natural killer cell number (NK#) despite their lower CD4 cell numbers and higher viral loads. In fact, there was no difference between the HLC group and the healthy community control group in NK# or NKCC. The NK findings were replicated at UCLA. A retrospective analysis showing that higher NKCC was related to fewer prior symptoms in the HLC group, and prospective analysis in the Comp group showing that NK# predicted a lower increase in viral load over 6 months further supported the importance of NK# and NKCC. CONCLUSIONS: Non-specific cellular immunity may be a factor protecting the health of HIV sero-positive individuals with very low CD4 cell counts.

The efficacy of whole cell pertussis immunisation: collected data on a vaccine produced in France.

The place of whole cell pertussis vaccines in paediatric immunisation schedules is under re-evaluation by public health authorities in many countries, with the expectation that the newly licensed acellular Bordetella pertussis vaccines will induce fewer adverse events while providing equivalent efficacy. In France, for instance, the CSHPF (Conseil supérieur d'hygiène public de France) recently modified its long-standing recommendation that French children only receive whole cell pertussis vaccine. Consequently, an acellular pertussis vaccine may be used for the first booster, at 16-18 months of age, and should be used for the reinforcing dose at 11-13 y of age. French children, nonetheless, continue to receive whole cell pertussis vaccine for the primary series immunisations at 2, 3, and 4 months, as the only whole cell pertussis vaccine available in France (licensed by Aventis Pasteur) has a long-established record of safety and protective efficacy. A review of its unpublished and published clinical results, obtained from studies throughout the world, demonstrates an efficacy of from 84-100% in six different retrospective analyses or outbreak investigations and a protective efficacy of 92% by clinical trial.

Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors.

The literature is reviewed and data are presented that relate to a model we have developed to account for the perpetuation of the perplexing disorder currently termed chronic fatigue syndrome (CFS). In patients with CFS there is chronic lymphocyte overactivation with cytokine abnormalities that include perturbations in plasma levels of proinflammatory cytokines and decrease in the ratio of Type 1 to Type 2 cytokines produced by lymphocytes in vitro following mitogen stimulation. The initiation of the syndrome is frequently sudden and often follows an acute viral illness. Our model for the subsequent chronicity of this disorder holds that the interaction of psychological factors (distress associated with either CFS-related symptoms or other stressful life events) and the immunologic dysfunction contribute to (a) CFS-related physical symptoms (e.g., perception of fatigue and cognitive difficulties, fever, muscle and joint pain) and increases in illness burden and (b) impaired immune surveillance associated with cytotoxic lymphocytes with resulting activation of latent herpes viruses.

Vaccine candidates in STD.

Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, particular scientific problems have delayed the development of an STD vaccine, such as incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of the human papillomavirus. It could be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that will include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, or (3) DNA plasmids expressing the vaccine antigen.

Autonomic and cardiovascular function in HIV spectrum disease: early indications of cardiac pathophysiology.

Autonomic dysfunction in persons with acquired immune deficiency syndrome (AIDS) has been reported previously but its incidence in early stage HIV infection and its relation to cardiovascular function have not been fully examined. The present study evaluated cardiovascular and autonomic function in 55 HIV-seronegative, and 52 HIV-asymptomatic and 31 HIV-symptomatic seropositive men. Measures of hemodynamic and autonomic function were obtained at rest and during a standardized battery of autonomic tests. Results were compared across groups while controlling for age, body mass, and physical activity. Analyses indicated that measures of autonomic function did not differ among groups. However, at rest, both HIV seropositive groups exhibited diminished stroke volume and elevated diastolic blood pressure, albeit within normotensive levels. In addition, the ability to sustain a blood pressure response during prolonged challenge and the relationship between stroke volume and baroreceptor/vagal responsiveness were disrupted in the HIV-symptomatic group. Therefore, in the pre-AIDS stages of infection, autonomic functioning appeared intact; yet alterations in baroreceptor/vagal function associated with depressed myocardial function may be an early warning signal reflecting cardiovascular pathological processes potentially exacerbated by HIV spectrum disease.

Haemophilus influenzae type b vaccine: reconstitution of lyophilised PRP-T vaccine with a pertussis-containing paediatric combination vaccine, or a change in the primary series immunisation schedule, may modify the serum anti-PRP antibody responses.

Immunogenicity data obtained after primary series immunisations against Haemophilus influenzae type b (Hib), using a vaccine prepared by conjugating the capsular polysaccharide of Hib to tetanus toxoid (ActHIB), were compiled from 146 study groups comprising 85 clinical trials or vaccination programs conducted between 1987 and 1999. ActHIB was administered as a monovalent lyophilised vaccine, injected either in association with another paediatric vaccine (at separate administration sites) or in combination (where the different vaccines are mixed together in the same syringe before injection). Review of these data reveals two trends. First, PRP-T vaccine, given either alone or in combination with DTwcP, resulted in a stronger anti-PRP serum antibody response than when PRP-T was combined with DTacP vaccine. Second, an accelerated (i.e. one-month interval) immunisation schedule tended to induce a poorer anti-PRP antibody response than did the more widely spaced, standard inoculation schedules. Although an in-depth analysis of these over 11000 study subjects on an individual basis with multivariate analysis or multifactorial statistical methods might eventually provide working hypotheses to fully understand these phenomenon, the various licensed, PRP-T-containing paediatric combination vaccines have proved to be clinically effective.

Rubella in the Russian Federation: epidemiological features and control measures to prevent the congenital rubella syndrome.

A review of the epidemiology of clinical rubella in the Perm region of the Russian Federation from 1979-97 showed that the incidence was about 220 cases per 100,000 population. Congenital rubella syndrome (CRS) accounted for 15% of birth defects and for about 3.5 cases of CRS per 1000 live births per year. Surveys of the seroepidemiology of rubella infection revealed that the susceptibility rate among pregnant women (i.e. rubella virus antibody haemagglutination-inhibition (HAI) assay titres < 10) was 16.5%. As serum rubella antibody HAI titres > or = 10 both prevented infection in pregnant women and protected their foetuses, serological testing has been introduced into the routine antenatal services. Pre-existing rubella antibodies were found not to interfere with the immune response to vaccination, so selective immunization was provided to girls approaching puberty and to women of childbearing age. A programme of epidemiological surveillance is being developed to define tactics for the widescale introduction of rubella vaccination.

Vaccines and infectious disease.

The exponential growth in vaccine research over the last decade, in which many infectious diseases now appear to be amenable to prevention through immunization, is built upon three factors: first, a richer understanding of the immune response (in particular, cellular immunity), second, a greater finesse in understanding the molecular biology of pathogenicity, and third, an expanding use of genetic engineering techniques either to create micro-organisms of greatly attenuated virulence that may be used as vaccines, or to sequence, and express, potential vaccine antigens. With respect to vaccines composed of purified antigens, parallel work is underway to develop immuno-modulating agents (adjuvants) that will selectively and safely induce the necessary immune response. Finally, within this plethora of vaccine candidates, vaccinologists are devoting much effort to alternatives to immunization via injection, such as administration of a vaccine through the mucosal route (e.g., oral, intranasal, intravaginal, etc.), through the transcutaneous route, and even by expression of vaccine antigens in edible fruits and vegetables.

The immunogenicity and reactogenicity of the trivalent vaccine, Trimovax, indicated for prevention of measles, mumps, and rubella, in 12-month-old children in Belarus.

In the Republic of Belarus, immunization of children against measles and mumps had been carried out using monovalent preparations according to the national schedule of measles vaccination at 12 months of age and mumps vaccination at 24 months of age. A rise of rubella incidence in the last few years (i.e., for the official registration period 1980 to 1998, there was an increase from 72.2 to 607.5 cases per 100,000 population) made it necessary to implement immunization against this infection, as well. Therefore, in 1996, combined vaccination against measles, mumps, and rubella of 12-month-old children was carried out for the first time in a clinical trial that used the vaccine Trimovax [Aventis Pasteur (formerly, Pasteur Mérieux Connaught), Lyon, France]. The reactogenicity of the vaccine was investigated in 372 children. Post-vaccination reactions were noted in 5.6% of children; in 1.3% of children the reactions were classified as severe [i.e. associated with body (axillary) temperature > or = 38.6 degrees C]. For the evaluation of immunogenicity, sera from 324 children were obtained 2 to 2.5 months after inoculation, and serum antibody levels were measured by enzyme immunoassays. Among the vaccines, protective antibody titers (expressed in inverse of dilution units) were observed to measles (> or = 1:50) in 97.8%, to mumps (> or = 1:50) in 93.8%, and to rubella (> or = 1:100) in 96.0% of children. Antibodies to all three components of the vaccine were mainly present in intermediate (1:200-1:800) or high (> or = 1:1600) titers: to measles in 96.3%; to mumps in 75.8%; and to rubella in 73.5% of vaccines. The results of these trials are evidence of the good safety and immunogenicity of this MMR vaccine, which provides an alternative to the currently used measles and mumps monovaccines, with the additional benefit of providing immunity against rubella, as well.

A TritonX-100-split virion influenza vaccine is safe and fulfills the committee for proprietary medicinal products (CPMP) recommendations for the European Community for Immunogenicity, in Children, Adults and the Elderly.

Influenza epidemics are an important cause of morbidity and mortality throughout the world. Current recommendations from Health Authorities emphasize annual immunization of people who are particularly at risk from an influenza virus infection; however, vaccination of working adults and of school children also has been shown to provide public health benefits. To give it a more advantageous reactogenicity profile than the diethylether-split influenza vaccines available previously, a split virion influenza vaccine has been produced with TritonX-100. In a series of clinical trials, Aventis Pasteur (formerly, Pasteur Mérieux Connaught) tested both the safety and immunogenicity of this TritonX-100-split virion influenza vaccine in 566 subjects (42 children, 296 adults, and 228 elderly adults) during three influenza seasons (1991, 1993, and 1995). The TritonX-100-split virion vaccine was well tolerated: no serious adverse events were recorded during the 21 days following immunization. Among the local reactions observed, mild pain, redness, or induration at the injection site were the most frequently reported. Fever (38.0 to 38.5 degrees C) was noted in five adults or elderly subjects (1%), and in two children (5%). Immunogenicity was determined by measuring serum haemagglutinin antibody titres specific to each vaccine virus strain. In each of the three vaccination campaigns, the TritonX-100-split virion influenza vaccine fulfilled the Notes for Guidance on Harmonization of Requirements for Influenza Vaccines outlined by the Committee for Proprietary Medicinal Products (CPMP) of the European Community for an influenza virus vaccine (i.e., seroprotection, seroconversion, or increase of geometric mean titre) in all age groups.

Cognitive-behavioral stress management reduces distress and 24-hour urinary free cortisol output among symptomatic HIV-infected gay men.

BACKGROUND: Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus (HIV). These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal (HPA) axis hormones such as cortisol, which has been related in other work to a down-regulation of immune system components relevant to HIV infection. The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men. METHODS: Symptomatic HIV-infected gay men who were randomized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine samples pre-post intervention. RESULTS: Of the 59 participants providing matched questionnaire data, men assigned to CBSM (n = 40) showed significantly lower posttreatment levels of self-reported depressed affect, anxiety, anger, and confusion than those in the wait-list control group (n = 19). Among the 47 men providing urine samples (34 CBSM, 13 controls), those assigned to CBSM revealed significantly less cortisol output as compared to controls. At the individual level, depressed mood decreases paralleled cortisol reductions over this period across the entire sample. CONCLUSION: A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress, especially depressed mood, paralleled greater decreases in cortisol over the intervention period. If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons, then interventions such as CBSM, which teaches them to relax, alter cognitive appraisals, use new coping strategies, and access social support resources, may decrease distress and depressed mood and normalize HPA axis functioning.

Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men.

The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on anxious mood, perceived stress, 24-hr urinary catecholamine levels, and changes in T-lymphocyte subpopulations over time in symptomatic HIV+ gay men. Seventy-three men were randomized to either a group-based CBSM intervention (n = 47) or a wait-list control (WLC) condition (n = 26). Men assigned to CBSM showed significantly lower posttreatment levels of self-reported anxiety, anger, total mood disturbance, and perceived stress and less norepinephrine (NE) output as compared with men in the WLC group. At the individual level, anxiety decreases paralleled NE reductions. Significantly greater numbers of T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were found 6 to 12 months later in those assigned to CBSM. Moreover, greater decreases in NE output and a greater frequency of relaxation home practice during the 10-week CBSM intervention period predicted higher CD3+CD8+ cell counts at follow-up.