The evolution of a neglected disease: tuberculosis discoveries in the centuries.

Tuberculosis (TB) and humans have coexisted for more than 40,000 years. The word "tuberculosis" derives from "tubercle", the histological lesion which appears in the organs, described by Pott in the late Eighteenth century and found, by molecular biology, in human skeletons dating back to 5000 BC. Early description of TB can be found in the writings of ancient India and China and in the Bible. In ancient Greece tuberculosis was not considered contagious, but Aristotle recognized the contagious nature of the pig's and ox's scrofula. The suspicion that phthisis is a contagious disease and that isolation can reduce the risk of transmission was expressed for the first time by the Arabian Avicenna, in his work "The canon of medicine". In 1699, the Health Council of the Republic of Lucca founded the "sanatorium" concept as place of care and isolation. In 1865 Villemain inoculated tubercular material from a human lymph node into a rabbit, obtaining for the first time the typical tubercular lesions. Some years later, on March 24, 1882, Robert Koch announced to the Berlin Society of Physiology the discovery of Mycobacterium tuberculosis. In the same period Virchow improved awareness of risk factors and correct behaviours among the general population. In 1952 Waksman won the Nobel Prize for the discovery of the first active drug against TB: streptomycin. Nevertheless, drug resistance appeared rapidly some years later and it is still a great challenge in TB fight nowadays.

The Spanish Influenza Pandemic: a lesson from history 100 years after 1918.

In Europe in 1918, influenza spread through Spain, France, Great Britain and Italy, causing havoc with military operations during the First World War. The influenza pandemic of 1918 killed more than 50 million people worldwide. In addition, its socioeconomic consequences were huge. "Spanish flu", as the infection was dubbed, hit different age-groups, displaying a so-called "W-trend", typically with two spikes in children and the elderly. However, healthy young adults were also affected. In order to avoid alarming the public, several local health authorities refused to reveal the numbers of people affected and deaths. Consequently, it was very difficult to assess the impact of the disease at the time. Although official communications issued by health authorities worldwide expressed certainty about the etiology of the infection, in laboratories it was not always possible to isolate the famous Pfeiffer's bacillus, which was, at that time, deemed to be the cause of influenza. The first official preventive actions were implemented in August 1918; these included the obligatory notification of suspected cases and the surveillance of communities such as day-schools, boarding schools and barracks. Identifying suspected cases through surveillance, and voluntary and/or mandatory quarantine or isolation, enabled the spread of Spanish flu to be curbed. At that time, these public health measures were the only effective weapons against the disease, as no vaccines or antivirals were available. Virological and bacteriological analysis of preserved samples from infected soldiers and other young people who died during the pandemic period is a major step toward a better understanding of this pandemic and of how to prepare for future pandemics.

The never-ending story of the fight against tuberculosis: from Koch's bacillus to global control programs.

Tuberculosis (TB) is one of the oldest diseases known to affect humanity, and is still a major public health problem. It is caused by the bacillus Mycobacterium tuberculosis (MT), isolated in 1882 by Robert Koch. Until the 1950s, X rays were used as a cheap method of diagnostic screening together with the tuberculin skin sensitivity test. In the diagnosis and treatment of TB, an important role was also played by surgery. The late Nineteenth century saw the introduction of the tuberculosis sanatorium, which proved to be one of the first useful measures against TB. Subsequently, Albert Calmette and Camille Guérin used a non-virulent MT strain to produce a live attenuated vaccine. In the 1980s and 1990s, the incidence of tuberculosis surged as a major opportunistic infection in people with HIV infection and AIDS; for this reason, a combined strategy based on improving drug treatment, diagnostic instruments and prevention was needed.

First Steps towards the Pharmaceutical Development of Ovules Containing Lactobacillus Strains: Viability and Antimicrobial Activity as Basic First Parameters in Vaginal Formulations.

In the majority of Latin-American countries, including Argentina, there is a limited availability of vaginal bioproducts containing probiotics in the market. In addition, the conventional treatments of genital tract infections in women represent a high cost to the public health systems. The future development of this type of bioproducts that employ specific lactobacilli strains would not only have a meaningful impact on women's health but would also represent a significant challenge to the pharmaceutical industry. The aims of the work described in this paper were (i) to study different pharmaceutical formulations of vaginal ovules containing Lactobacillus fermentum L23 and L. rhamnosus L60, to determine in which formulation lactobacilli viability was sustained for longer time and (ii) to evaluate if probiotic strains maintained both the antimicrobial activity and biofilm-producing ability after being recovered from the ovules. In this study, we developed and characterized three pharmaceutical formulations containing different glycerol amounts and specific lactobacilli strains. Three relevant parameters, cell viability, antimicrobial activity, and biofilm production, by lactobacilli recovered from the ovules were tested. Although the viability of L23 and L60 strains was mainly influenced by high ovule's glycerol proportion, they survived at 4 °C during the 180 days. Both lactobacilli's antimicrobial activity and biofilm-producing ability were maintained for all treatments. In conclusion, employing a much reduced number of components, we were able to select the most suitable pharmaceutical formulation which maintained not only lactobacilli viability for a long period of time but also their antimicrobial activity and biofilm-producing ability.

The history of tuberculosis: the social role of sanatoria for the treatment of tuberculosis in Italy between the end of the 19th century and the middle of the 20th.

Since ancient times, the most frequently prescribed remedy for the treatment of tuberculosis was a stay in a temperate climate. From the middle of the 19th century to the middle of the 20th, Europe saw the development of sanatoria, where patients were able to benefit from outdoor walks, physical exercise and a balanced diet. Moreover, the institutionalisation and isolation of patients deemed to be contagious remains one of the most efficacious measures for the control of this type of infection. The first sanatorium opened in Germany in 1854, while in Italy the earliest experiments were conducted at the beginning of the 20th century. At that time, it was widely believed in Italy that pulmonary tuberculosis could improve in a marine climate. By contrast, the scholar Biagio Castaldi described the salubrious effects of mountain air and documented a lower incidence of tuberculosis among mountain populations, which supported the hypothesis of a hereditary predisposition to the disease. In 1898, several local committees (Siena, Pisa, Padua) were founded to fight tuberculosis. The following year, these gave rise to the Lega Italiana (Italian League) under the patronage of the King of Italy, which helped to promote state intervention in the building of sanatoria. The pioneer of the institution of dedicated facilities for the treatment of tuberculosis was Edoardo Maragliano in Genoa in 1896. A few years later, in 1900, the first specialised hospital, with a capacity of 100 beds, was built in Budrio in a non-mountainous area, the aim being to treat patients within their habitual climatic environment. In the following years, institutes were built in Bologna, Livorno, Rome, Turin and Venice. A large sanatorium for the treatment of working-class patients was constructed in Valtellina by the fascist government at the beginning of the century, in the wake of studies by Eugenio Morelli on the climatic conditions of the pine woods in Sortenna di Sondalo, which he deemed to be ideal. In December 1916, the Italian Red Cross inaugurated the first military sanatorium in the "Luigi Merello" maritime hospice in Bergeggi (SV) to treat soldiers affected by curable tuberculosis. In 1919, a specific law mandated a 10-fold increase in funding for the construction of dispensaries and sanatoria. As a result, the Provincial Anti-tuberculosis Committees were transformed into Consortiums of municipal and provincial authorities and anti-TB associations, with the aim of coordinating the action to be undertaken. In 1927, the constitution of an Anti-tuberculosis Consortium in every province became a legal obligation. Despite this growth in social and healthcare measures, tuberculosis in Italy continued to constitute a major public health problem until the advent of antibiotics in the 1950s. Until that time, the sanatorium played a leading role in the treatment of tuberculosis in Italy, as in the rest of Europe.

The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus.

Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium tuberculosis (MT) that has always been a permanent challenge over the course of human history, because of its severe social implications. It has been hypothesized that the genus Mycobacterium originated more than 150 million years ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of TB. The illness was known in England and France as "king's evil", and it was widely believed that persons affected could heal after a royal touch. In 1720, for the first time, the infectious origin of TB was conjectured by the English physician Benjamin Marten, while the first successful remedy against TB was the introduction of the sanatorium cure. The famous scientist Robert Koch was able to isolate the tubercle bacillus and presented this extraordinary result to the society of Physiology in Berlin on 24 March 1882. In the decades following this discovery, the Pirquet and Mantoux tuberculin skin tests, Albert Calmette and Camille Guérin BCG vaccine, Selman Waksman streptomycin and other anti-tuberculous drugs were developed.

History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines.

Influenza is a highly infectious airborne disease with an important epidemiological and societal burden; annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths. A hundred years after this virus was first isolated, influenza vaccines are an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. Innovative tools, such as recombinant technologies and intra-dermal devices, are currently being investigated in order to improve the immunological response. The recurring mutations of influenza strains has prompted the recent introduction of a quadrivalent inactivated vaccine. In the near future, scientific research will strive to produce a long-lasting universal vaccine containing an antigen that will offer protection against all influenza virus strains.

Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden.

Influenza illness is caused by influenza A and influenza B strains. Although influenza A viruses are perceived to carry greater risk because they account for the majority of influenza cases in most seasons and have been responsible for influenza pandemics, influenza B viruses also impose a substantial public health burden, particularly among children and at-risk subjects. Furthermore, since the 2001-2002 influenza season, both influenza B lineages, B/Victoria-like viruses and B/Yamagata-like viruses have co-circulated in Europe. The conventional trivalent influenza vaccines have shown a limited ability to induce effective protection when major or minor mismatches between the influenza B vaccine component and circulating strains occur. For this reason, the inclusion of a second B strain in influenza vaccines may help to overcome the well-known difficulties of predicting the circulating B lineage and choosing the influenza B vaccine component. Two quadrivalent influenza vaccines, a live-attenuated quadrivalent influenza vaccine (Q/LAIV) and a split inactivated quadrivalent influenza vaccine (I/QIV), were first licensed in the US in 2012. Since their introduction, models simulating the inclusion of QIV in influenza immunization programs have demonstrated the substantial health benefits, in terms of reducing the number of influenza cases, their complications and mortality. In the near future, evaluations from simulation models should be confirmed by effectiveness studies in the field, and more costeffectiveness analyses should be conducted in order to verify the expected benefits.

Available influenza vaccines: immunization strategies, history and new tools for fighting the disease.

The main public health strategy for containing influenza-related disease is annual vaccination, which is recommended for the elderly and others belonging to risk-factor categories, who present the highest morbidity and mortality, as reported by the World Health Organization (WHO) Recommendations. The availability of different influenza vaccine formulations makes the choice of the best immunization strategy a challenge for stakeholders and public health experts. Heterogeneity in at-risk categories included in national influenza vaccine recommendations still exists, in particular among European countries. Broader consensus is expected, which should positively impact on influenza vaccination coverage. The availability of quadrivalent vaccines, containing both influenza B lineages, offers the potential to improve protection by overcoming the drawbacks of wrongly predicting which B lineage will predominate in a given year.

Determinants of adherence to seasonal influenza vaccination among healthcare workers from an Italian region: results from a cross-sectional study.

OBJECTIVES: Notwithstanding decades of efforts to increase the uptake of seasonal influenza (flu) vaccination among European healthcare workers (HCWs), the immunisation rates are still unsatisfactory. In order to understand the reasons for the low adherence to flu vaccination, a study was carried out among HCWs of two healthcare organisations in Liguria, a region in northwest Italy. METHODS: A cross-sectional study based on anonymous self-administered web questionnaires was carried out between October 2013 and February 2014. Through univariate and multivariate regression analysis, the study investigated the association between demographic and professional characteristics, knowledge, beliefs and attitudes of the study participants and (i) the seasonal flu vaccination uptake in the 2013/2014 season and (ii) the self-reported number of flu vaccination uptakes in the six consecutive seasons from 2008/2009 to 2013/2014. RESULTS: A total of 830 HCWs completed the survey. Factors statistically associated with flu vaccination uptake in the 2013/2014 season were: being a medical doctor and agreeing with the statements 'flu vaccine is safe', 'HCWs have a higher risk of getting flu' and 'HCWs should receive flu vaccination every year'. A barrier to vaccination was the belief that pharmaceutical companies influence decisions about vaccination strategies. DISCUSSION: All the above-mentioned factors, except the last one, were (significantly) associated with the number of flu vaccination uptakes self-reported by the respondents between season 2008/2009 and season 2013/2014. Other significantly associated factors appeared to be level of education, being affected by at least one chronic disease, and agreeing with mandatory flu vaccination in healthcare settings. CONCLUSIONS: This survey allows us to better understand the determinants of adherence to vaccination as a fundamental preventive strategy against flu among Italian HCWs. These findings should be used to improve and customise any future promotion campaigns to overcome identified barriers to immunisation.

Pneumococcal vaccination strategies in adult population: perspectives with the pneumococcal 13 - valent polysaccharide conjugate vaccine.

Streptococcus pneumoniae (Sp) is a leading cause of infection in people of all ages worldwide, determining a significant impact because of its relatively high incidence rate, the associated economic costs, and the high case-fatality rates. More attention has to be paid for elderly and people with one or more risk factors, in order to reduce health costs and pneumococcal hospital admissions. Moreover, the increasing incidence of antibiotic-resistant Sp strains is a source of concern for its relevant clinical importance in health-care settings. At present, the 23-valent polysaccharide (PPV23) vaccine has shown some limits in terms of protection in the elderly population and against invasive diseases, among adults affected with chronic diseases, non-bacteriemic pneumonias and with immune suppression, in particular in adults with HIV. In December 2011, FDA licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for prevention of pneumonia and invasive diseases (IPDs) in adults aged ≥50 years. The same decision was concomitantly assumed in Europe by EMA. PCV13 has shown superior results both in terms of immunogenicity and of adequate stimulation of a stable and long-lasting immunological memory. European recommendations for PCV13 vaccination in adults are still heterogeneous between Countries. The availability of PCV13 for adults offer a new and promising tool against Sp IPDs and non-IPDs, especially in elderly and at risk populations.

Resistência bacteriana e ação das bacteriocinas de Lactobacillus spp em Staphylococcus aureus isolados de mastite bovina / Bacterial resistance and bacteriocins action in Staphylococcus aureus isolated from bovine mastitis

Staphylococcus aureus is the major pathogen causing intramammary infections in dairy cattle worldwide. Among the factors that contribute to its spread and infectious potential is the ability to overcome the mechanisms of antimicrobials activity. The present work investigated the antimicrobial resistance pattern and sensibility to bacteriocins produced by strains of Lactobacillus spp of 30 isolates of S. aureus from mastitis. From this, 29 are beta-lactamase producers. Eight isolates (26.6 percent) showed resistance to at least four antibiotics being considered multiresistent. All of them were mecA-positive. Otherwise, all isolates tested showed sensibility to at least one of the four bacteriocin producer strains. Due to the significant depletion of the efficacy of antimicrobials, pathogen growth inhibition by bacteriocins seems an alternative of biological control in infectious processes.

Morphological variation of Aechmea distichantha (Bromeliaceae) in a Chaco forest: habitat and size-related effects.

Plants show different morphologies when growing in different habitats, but they also vary in their morphology with plant size. We examined differences in sun- and shade-grown plants of the bromeliad Aechmea distichantha with respect to relationships between plant size and variables related to plant architecture, biomass allocation and tank water dynamics. We selected vegetative plants from the understorey and from forest edges of a Chaco forest, encompassing the whole size range of this bromeliad. Plant biomass was positively correlated with most architectural variables and negatively correlated with most biomass allocation variables. Understorey plants were taller and had larger diameters, whereas sun plants had more leaves, larger sheath area, sheath biomass and sheath mass fraction. All tank water-related variables were positively correlated with plant biomass. Understorey plants had a greater projected leaf area, whereas sun plants had higher water content and evaporative area. Plasticity indices were higher for water-related than for allocation variables. In conclusion, there were architectural and biomass allocation differences between sun- and shade-grown plants along a size gradient, which, in turn, affected tank water-related variables.

Antimicrobial sensitivity and adherence study in strains of coagulase-negative Staphylococcus spp.

Antimicrobial sensitivity was evaluated from 120 strains of coagulase-negative Staphylococcus (CoNS), isolated from urinary infections. The isolated species were identified by conventional methods and sensitivity to vancomycin, tetracyclin, norfloxacin, cephalothin erythromycin, clindamycin, oxacillin, penicillin, cyprofloxacin, ampicillin and ampicillin/sulbactam was tested by the agar dilution technique and the diffusion in disc technique. The distribution of the species was: Staphylococcus epidermidis 26 (21.6%), S. haemolyticus 48 (40.0%), S. saprophyticus 40 (33.4%) and S. simulans 6 (5%). CoNS strains extracted from urinary infections showed a high percentage of vancomycin and tetracyclin sensitivity, and a low sensitivity to beta-lactamic antibiotics, except ampicillin/sulbactam and cephalotin. Isolation percentage resistance to oxacillin was less than 48%. Strains resistant to oxacillin were considered as resistant to both penicillin and ampicillin. From 42% to 80% of S. haemolyticus, S. saprophyticus, Staphylococcus epidermidis and S. simulans were positive to the adherence test. Results from this work showed that slime producing CoNS strains, isolated in Río Cuarto Hospital, had different percentages of resistance to the studied antimicrobial agents.

Epidemiology of sexually transmitted diseases in Río Cuarto, Argentina.

Sexually transmitted diseases (STD) are a group of transmittable diseases acquired fundamentally through sexual contact. STD are a social problem resulting from demographic explosion and changes in sexual conduct, which affects teenagers and adults of all socioeconomic strata. The goal of this work was to establish the actual state of the different STD within the studied population. Samples of vaginal fluids, endocervical materials and urethral exudates taken from 2,630 patients during five years were processed. 1,341 samples tested positive to one or more of the microorganisms, 1,099 corresponding to female patients and 242 to male patients. The microorganisms found in women were: Gardnerella vaginalis (39.1%), Candida albicans (21.3%), Trichomonas vaginalis (16.8%), Chlamydia trachomatis (11.5%); Neisseria gonorrhoeae (3.4%), Mycoplasma hominis (2.6%); Ureaplasma urealyticum (4.1%) and Treponema pallidum (1.6%). Associations were: Gardnerella vaginalis with Trichomonas vaginalis (6%), Gardnerella vaginalis with Candida albicans (5.1%); Trichomonas vaginalis with Neisseria gonorrhoeae (2.2%) and Gardnerella vaginalis with Chlamydia trachomatis (2.1%). In men, gonococcic urethritis represented 37.8%, non-gonococcic urethritis 55.4% and Treponema pallidum 6.8%. A decrease in syphilis, gonococcic urethritis and gonococcic cervicitis was observed, increasing the prevalence of non-gonococcic urethritis and cervicitis. This study showed that in our environment the actual tendency of STD is still high.

Prevalencia de Chlamydia trachomatis, micoplasmas urogenitales y sus asociaciones en un grupo de mujeres promiscuas / Prevalence of Chlamydia trachomatis, urogenital micoplasmas and their association to a group of promiscuous women

Chalamydia trachomatis, Ureaplasma urealyticum y Mycoplasma hominis son microorganismos responsables de infecciones urogenitales. Son aislados con considerable frecuencia del tracto genital femenino. En este trabajo se estudiaron 100 exudados vaginales de mujeres promiscuas que concurrieron a la división de Bacteriología del Hospital Central de Río Cuarto. En todas las muestras se investigó la presencia de C. trachomatis, U. urealyticum, M. hominis. La prevalencia hallada fue: C. trachomatis 17 por ciento; U. urealyticum 57 por ciento; M. hominis 21 por ciento y Neisseria gonorrhoeae 2 por ciento. Las asociaciones más frecuentes fueron: C. trachomatis-Trichomonas vaginalis, micoplasmas-T. vaginalis y Gardnerella vaginalis-Candida albicans con un 18 por ciento, 15 por ciento y 8 por ciento respectivamente

[A biotype study of Gardnerella vaginalis isolated from patients with and without symptoms of bacterial vaginosis]. / Estudio de los biotipos de Gardnerella vaginalis, aisladas de pacientes con y sin síntomas de vaginosis bacteriana.

METHODS: A simple and reproducible proposed for Benito et al. scheme for identification biotypes of Gardnerella vaginalis has been developed, based on reactions for lipase, hippurate, hydrolysis, and beta-galactosidase. RESULTS: 11 biotypes were found among 130 strains from women with and without bacterial vaginosis (non-specific vaginitis) 1A, 5B; 8B, 5C, 8C, 1E, 6G and 7G in women with vaginosis and the biotypes 1A, 5B, 8B, 1C, 8F and 6H in women without vaginosis. These biotypes 1A; 5B and 8B were found in two groups. CONCLUSIONS: These data suggest that some biotypes of G. vaginalis are associated with bacterial vaginosis.

[Survey of sexually transmitted diseases in the region of Rio Cuarto]. / Relevamiento de las enfermedades de transmisión sexual en la región de Río Cuarto.

Sexually transmitted diseases (STD) are acquired mainly through sexual intercourse, being one of the most frequent groups of infectious diseases worldwide and consequently an important public health problem. The aim of this paper was to determine the current state of STD and to compare different diagnostic methods in the population studied. A total of 1060 samples from vaginal flows, endocervical material and urethral discharge were studied during 3 years. Of the total samples, 583 were positive, 493 in women and 90 in men. Microorganisms found in women were: Gardnerella vaginalis (39.3%), Candida albicans (21.1%), Trichomonas vaginalis (17.3%), Candida trachomatis (11.3%), Neisseria gonorrhoeae (3.2%): Mycoplasma hominis and Ureaplasma urelyticum (6.5%) and Treponema pallidum (1.4%), the associations found were, Gardnerella vaginalis with Trichomonas vaginalis 5.5%; Gardnerella vaginalis with Candida albicans 4.9%; Trichomonas vaginalis with Neisseria gonorrhoeae (2.2%) and Gardnerella vaginalis with Chlamydia trachomatis (1.9%). In men, gonococcal urethritis (UG) represented 37.7% non UG 55.6% and Treponema pallidum 6.7%. These results indicate a decrease in sifilis and in UG when compared to previous studies showing that gonococcal cervicitis had also decreased. We found an important increase in the prevalence of urethritis and non gonococcal cervicitis in agreement with world statistics which consider these diseases as the most common venereal ones. It is necessary to increase the search for Chlamydia trachomatis in pregnant women due to vertical transmission. It should be noted that, in spite of certain fluctuations, the incidence of the STD in our area is still unacceptably high.

Detección de Chlamydia trachomatis por enzimo inmunoensayo con anticuerpos monoclonales en mujeres sexualmente activas / Detection of chlamydia trachomatis by enzyme immunoassay with monoclonal antibodies in sexualy active women

El objetivo de este trabajo fue evaluar la prevalencia de las infecciones producidas por Chlamydia trochomatis en pacientes que concurrieron al servicio de Ginecología. Se estudiaron 369 pacientes mujeres, sexualmente activas que consultaron por presencia de flujo y/o síntomas de cervicitis. Para la detección de antígenos clamidiales se usó un enzimoinmunoensayo con anticuerpos monoclonales específicos (Chlamyfast). La prevalencia de las infecciones por C. trachomatis en la población estudiada fue del 15,17 por ciento (56/369). El 71,4 por ciento (40/56) de las mujeres fueron sintomáticas y el 28,6 por ciento (16/56), asintomáticas (P < 0,00001). La mayor incidencia se observó en el grupo de mujeres cuyas edades oscilaron entre 21 y 30 años (21/149)