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INTRODUCTION: Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus. METHODS: Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors. RESULTS: 152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62). CONCLUSION: In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.

Introducción: A pesar de las mejoras en los cuidados de la salud, la mortalidad asociada a neumonía continúa siendo alta. El objetivo de este estudio fue analizar los factores asociados a mortalidad en neumonía bacteriémica por neumococo. Métodos: Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de neumonía y neumococo aislado en hemocultivos, entre enero 2012 y mayo 2021. Se analizaron: variables clínicas y de laboratorio, compromiso radiológico, evolución y mortalidad durante la internación. Se comparó el grupo de pacientes fallecidos con el de sobrevivientes. Resultados: Se incluyeron 152 pacientes. La mediana de edad fue de 58 años y el 58.9% fueron hombres. El 33% presentó un CURB-65 mayor a 2 al momento de internación. La mortalidad global fue 34% (n=52). Los pacientes fallecidos se encontraban más frecuentemente taquipneicos al ingreso (frecuencia respiratoria 26 vs. 22; p=0.003), presentaban más frecuentemente alteración del sensorio (58% vs. 14%; p< 0.001), PaO2/fracción inspirada de oxígeno (PAFI) < 250 (58% vs. 22%; p<0.001), compromiso radiológico bilateral (50% vs. 32%; p=0.03), necesidad de asistencia respiratoria mecánica (ARM) (50% vs. 12%; p< 0.001), mayor valor de creatinina en sangre (1.6 vs. 1.15; p=0.01), menor recuento de glóbulos blancos (10 900 vs. 17 400; p=0.002), menor valor de glucemia (111 vs. 120; p=0.01) y menos días de estancia hospitalaria (6 vs. 9; p=0.015). En el análisis de regresión logística multivariable se mantuvieron diferencias significativas en los siguientes factores asociados a mortalidad: ventilación mecánica (OR=3.54), confusión (OR=5.95), radiografía con compromiso bilateral (OR= 3.20) y PAFI < 250 (OR=3.62). Conclusión: Los factores relacionados con mortalidad, a pesar de la presencia de bacteriemia, no difieren de los publicados en la literatura y forman parte de los scores pronósticos de práctica habitual.

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Adult smokers, those with comorbidities, and the elderly, are at greater risk of contracting infections and their complications. Community acquired respiratory infections due to viruses, pneumococcus and other bacteria, affect both healthy and sick adults. There are vaccines that the pulmonologist must know and prescribe. The target strains of the influenza vaccine are defined by the WHO for the Southern hemisphere considering those involved in the previous influenza season in the Northern hemisphere. Its effectiveness depends on virulence, concordance between circulating and vaccine strains, and population coverage. The anti-pneumococcal polysaccharide vaccine available since 1983 is being replaced by more effective conjugate vaccines to prevent infections related to serotypes present in them. Immunization against SARS-CoV-2 reduced the contagion, severity, and lethality of COVID-19. The acellular vaccine against Bordetella pertussis for adults is present for specific situations in the adult calendar; vaccinating them strengthens the control of childhood contagion. The double (diphtheria + tetanus), and triple (double + pertussis) bacterial vaccines, and the vaccines against measles, chickenpox, rubella, human papillomavirus, Haemophilus influenzae, meningococcus, herpes zoster, Argentine hemorrhagic fever and yellow fever, are of a more limited use. Soon we will have new vaccines such as the one recently approved by the FDA against respiratory syncytial virus. Through a consensus of experts in respiratory infections, we review the new evidence regarding the immunization of adults who consult a pulmonologist, and thus update the recommendations on vaccination made eight years ago.

Los adultos fumadores con comorbilidades, y los ancianos, corren mayor riesgo de contraer infecciones y sus complicaciones. Las infecciones respiratorias comunitarias por virus, neumococo y otras bacterias afectan tanto a adultos sanos como enfermos. Existen vacunas que el neumonólogo debe conocer y prescribir. Las cepas blanco de la vacuna contra influenza son definidas por la OMS para el hemisferio sur considerando a las implicadas en la temporada precedente de influenza en el hemisferio norte. Su efectividad depende de la virulencia, la concordancia entre las cepas circulantes y las vacunales y la cobertura de la población. La vacuna anti-neumocócica polisacárida disponible desde 1983 está siendo reemplazada por vacunas conjugadas más eficaces para prevenir infecciones relacionadas a serotipos presentes en las mismas. La inmunización contra SARS-CoV-2 redujo el contagio, la gravedad y la letalidad de COVID-19. La vacuna acelular contra Bordetella pertussis para adultos está presente para situaciones puntuales en el calendario para adultos, vacunarlos fortalece el control del contagio infantil. Las vacunas doble bacteriana (difteria + tétanos), y triple (doble + pertussis), y contra sarampión, varicela, rubeola, virus del papiloma humano, Haemophylus influenzae, meningococo, herpes zóster, fiebre hemorrágica argentina y fiebre amarilla, son de uso más limitado. Pronto contaremos con nuevas vacunas, como la recientemente aprobada por la FDA contra el virus sincicial respiratorio. Revisamos a través de un consenso de expertos en infecciones respiratorias las nuevas evidencias acerca de la inmunización de adultos que consultan al neumonólogo, y actualizamos así las recomendaciones sobre vacunación realizadas ocho años atrás.

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RESUMEN Los adultos fumadores, con comorbilidades, y los ancianos tienen mayor riesgo de contraer infecciones pulmonares y de tener peor evolución. La neumonía adquirida en la comunidad debida a virus, neumococo, además de otras bacterias y microorga nismos "atípicos" afecta tanto a adultos sanos como enfermos. La vacuna antigripal se diseña el verano anterior orientada a las cepas esperadas para la temporada siguiente. Su eficacia depende fundamentalmente de la variante viral que finalmente sea la responsable del brote. La vacuna anti-neumocócica polisacárida existe desde 1983 y será inexorablemente reemplazada por vacunas conjugadas de mayor eficacia, que previenen la infección por los serotipos presentes en la vacuna. La inmunización contra SARS-CoV-2 aceleró la reducción del contagio y la gravedad de COVID-19 notablemente. La vacuna acelular para Bordetella pertussis no está en el calendario de adultos, aun cuando vacunarlos fortalece el control del contagio infantil. La vacunas doble bacteriana (difteria y tétanos), y triple (doble + pertusis), y contra sarampión, varicela, rubeola, HPV, Haemophylus influenzae, meningococo, herpes zóster, fiebre hemorrágica argentina y fiebre amarilla están disponibles, pero son de uso limitado. Nuevas vacunas, como la recientemente aprobada por los CDC contra el virus sincicial respiratorio, pronto estarán disponibles.

ABSTRACT Adult smokers, subjects with comorbidities, and the elderly are at higher risk of pulmo nary infections and worse outcomes. Community-acquired pneumonia due to viruses, pneumococcus, other bacteria, and "atypical" microorganisms affects healthy and sick adults. The flu vaccine is designed the previous summer for the strains expected for the following season. Its effectiveness depends fundamentally on the viral variant ultimately responsible for the outbreak. The anti-pneumococcal polysaccharide vaccine has been available since 1983 and it is expected to be replaced by conjugate vaccines which are more effective in preventing infection due to serotypes present in the vaccine. Immuniza tion against SARS-CoV-2 diminished contagion and severity of COVID-19 remarkably. The acellular vaccine for Bordetella pertussis is not on the schedule for all adults, even when vaccinating them strengthens the control of contagion in children. Double bacterial (diphtheria and tetanus), triple (double + pertussis), measles, varicella, rubella, HPV, Haemophilus influenzae, meningococcal, herpes zoster, Argentine hemorrhagic fever, and yellow fever vaccines are available, but their use is limited. New vaccines such as the one recently approved by the CDC against respiratory syncytial virus will soon be available.

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Resumen Los adultos fumadores con comorbilidades, y los ancianos, corren mayor riesgo de contraer infecciones y sus complicaciones. Las infecciones respiratorias comu nitarias por virus, neumococo y otras bacterias afectan tanto a adultos sanos como enfermos. Existen vacunas que el neumonólogo debe conocer y prescribir. Las ce pas blanco de la vacuna contra influenza son definidas por la OMS para el hemisferio sur considerando a las implicadas en la temporada precedente de influenza en el hemisferio norte. Su efectividad depende de la virulencia, la concordancia entre las cepas circulantes y las vacunales y la cobertura de la población. La vacuna anti-neumocócica polisacárida disponible desde 1983 está siendo reemplazada por vacunas conjugadas más eficaces para prevenir infecciones relacionadas a sero tipos presentes en las mismas. La inmunización contra SARS-CoV-2 redujo el contagio, la gravedad y la letalidad de COVID-19. La vacuna acelular contra Bordetella pertussis para adultos está presente para situaciones puntuales en el calendario para adultos, vacunarlos fortalece el control del contagio infantil. Las vacunas doble bacte riana (difteria + tétanos), y triple (doble + pertussis), y contra sarampión, varicela, rubeola, virus del papiloma humano, Haemophylus influenzae, meningococo, herpes zóster, fiebre hemorrágica argentina y fiebre amarilla, son de uso más limitado. Pronto contaremos con nuevas vacunas, como la recientemente aprobada por la FDA contra el virus sincicial respiratorio. Revisamos a través de un consenso de expertos en infecciones respiratorias las nuevas evidencias acerca de la inmunización de adultos que consultan al neumonólogo, y actualizamos así las recomendaciones sobre vacunación realizadas ocho años atrás.

Abstract Adult smokers, those with comorbidities, and the elderly, are at greater risk of contracting infections and their complications. Community acquired respiratory infections due to viruses, pneumococcus and other bac teria, affect both healthy and sick adults. There are vac cines that the pulmonologist must know and prescribe. The target strains of the influenza vaccine are defined by the WHO for the Southern hemisphere considering those involved in the previous influenza season in the Northern hemisphere. Its effectiveness depends on virulence, concordance between circulating and vaccine strains, and population coverage. The anti-pneumococcal polysaccharide vaccine available since 1983 is being replaced by more effective conjugate vaccines to pre vent infections related to serotypes present in them. Immunization against SARS-CoV-2 reduced the conta gion, severity, and lethality of COVID-19. The acellular vaccine against Bordetella pertussis for adults is present for specific situations in the adult calendar; vaccinating them strengthens the control of childhood contagion. The double (diphtheria + tetanus), and triple (double + pertussis) bacterial vaccines, and the vaccines against measles, chickenpox, rubella, human papillomavirus, Haemophilus influenzae, meningococcus, herpes zoster, Argentine hemorrhagic fever and yellow fever, are of a more limited use. Soon we will have new vaccines such as the one recently approved by the FDA against respi ratory syncytial virus. Through a consensus of experts in respiratory infections, we review the new evidence regarding the immunization of adults who consult a pulmonologist, and thus update the recommendations on vaccination made eight years ago.

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National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other preventable vaccine diseases. The aim of this article is to estimate the vaccine coverage in adults aged 65 years and older and to analyse the factors that could increase or decrease vaccination uptake probability for the three listed vaccines in the national vaccination programme (influenza, tetanus and diphtheria, and pneumococcus) and the full scheme in Mexico. We conducted an analytical cross-sectional study with 2012, 2018, and 2021 rounds from the National Health and Nutrition Survey, in which we calculated the vaccine coverage estimations and performed multivariable logistic regression models to analyse the factors related to vaccine uptake. Tetanus and diphtheria vaccines had the greatest coverage estimation in all years (59-71%), whereas the pneumococcus vaccine had the lowest (32-53%). Full scheme vaccine coverage decreased from 37.80% to 24.77% in 2012 and 2021, respectively. The National Health Card property, morbidity, being a beneficiary of any health system institution, and use of preventive services increased the probability of vaccine uptake. In conclusion, vaccine coverage in older Mexican adults decreased over time, and the Mexican health system plays a strategic role in immunisation.

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HIV-infected patients are at particular risk for invasive pneumococcal disease (IPD). We describe cases of IPD in people living with HIV/AIDS (PLWHA) and find associated risk factors for infection and death. METHODS: A retrospective case-control study, nested in a cohort, including PLWHA with and without IPD, conducted in Brazil, 2005-2020. Controls were of the same gender/age and seen at the same time/place as cases. RESULTS: We identified 55 episodes of IPD (cases) in 45 patients and 108 controls. The incidence of IPD was 964/100,000 person-years. A total of 42 of 55 (76.4%) IPD episodes presented with pneumonia and 11 (20%) with bacteremia without a focus and 38/45 (84.4%) were hospitalized. Blood cultures were positive in 54/55 (98.2%). Liver cirrhosis and COPD were the only factors associated with IPD in PLWHA in univariate analysis, although no associated factors were found in multivariate analysis. Penicillin resistance was found in 4/45 (8.9%). Regarding antiretroviral therapy (ART), 40/45 (88.9%) cases vs. 80/102 controls (74.1%) were in use (p = 0.07). Patients with HIV and IPD had a higher CD4 count of 267 cells/mm3 compared with the control group, in which it was 140 cells/mm3 (p = 0.027). Pneumococcal vaccination was documented in 19%. Alcoholism (p = 0.018), hepatic cirrhosis (p = 0.003), and lower nadir CD4 count (p = 0.033) were associated with the risk of death in patients with IPD. In-hospital mortality among PLWHA and IPD was 21.1%, and it was associated with thrombocytopenia and hypoalbuminemia, elevated band forms, creatinine, and aspartate aminotransferase (AST). CONCLUSIONS: The incidence of IPD in PLWHA remained high despite ART. The vaccination rate was low. Liver cirrhosis was associated with IPD and death.

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Abstract Objective: To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010. Data source: A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis. Summary of the findings: Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%-44.6% of all IPD in children under 5 yrs. Conclusions: PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.

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OBJECTIVE: To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010. DATA SOURCE: A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis. SUMMARY OF THE FINDINGS: Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%-44.6% of all IPD in children under 5 yrs. CONCLUSIONS: PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.

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Licensed glycoconjugate vaccines are generally prepared using native or sized polysaccharides coupled to a carrier protein through random linkages along the polysaccharide chain. These polysaccharides must be chemically modified before covalent linking to a carrier protein in order to obtain a more defined polysaccharide structure that leads to a more rational design and safer vaccines. There are classic and new methods for site-selective glycopolysaccharide conjugation, either chemical or enzymatic modification of the polysaccharide length or of specific amino acid residues of the protein carrier. Here, we discuss the state of the art and the advancement of conjugation of S. pneumoniae glycoconjugate vaccines based on pneumococcal capsular polysaccharides to improve existing vaccines.

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A meningite bacteriana é uma inflamação das leptomeninges que envolvem o Sistema Nervoso Central. Essa patologia, que possui diversos agentes etiológicos, apresenta-se na forma de síndrome, com quadro clínico grave. Entre as principais bactérias que causam a meningite, estão a Neisseria meningitis e Streptococcus pneumoniae. A transmissão ocorre através das vias aéreas por meio de gotículas, sendo a corrente sanguínea a principal rota para as bactérias chegarem à barreira hematoencefálica e, a partir dessa, até as meninges. Atualmente existem vários métodos de diagnóstico precisos, onde a cultura de líquido cefalorraquidiano (LCR) é o método padrão ouro. Ademais, a melhora na qualidade do tratamento com beta-lactâmicos e a maior possibilidade de prevenção, devido à elevação do número e da eficácia de vacinas, vem contribuindo para redução dos casos da doença e de sua gravidade. Porém, apesar desses avanços, ainda há um elevado número de mortalidades e sequelas causadas por essa síndrome.

Bacterial meningitis is an inflammation of the leptomeninges that surround the Central Nervous System. This pathology, which has several etiological agents, is presented as a syndrome with a severe clinical scenario. The main bacteria causing meningitis include Neisseria meningitis and Streptococcus pneumoniae. It can be transmitted by droplets through the airways, with the bacteria using the bloodstream as the main route to reach the blood-brain barrier, and from there to the meninges. There are currently several accurate diagnostic methods, with CSF culture being the gold standard. In addition, the improvement in the quality of beta-lactam treatment and the greater possibility of prevention due to the increased number and effectiveness of vaccines have contributed to reducing the number of cases and severity of the disease. Nevertheless, despite these advances, this syndrome still presents a high number of mortalities and sequelae.

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The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.

RESUMO

The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.

RESUMO

Cardiovascular diseases are the leading cause of death in most regions of the world, usually followed by infectious diseases. For decades, infections in general, and particularly those involving the respiratory system, have been known to be associated with an increased risk of cardiovascular and cerebrovascular events, and their consequent morbidity and mortality. Although vaccines are an excellent strategy in the prevention of infectious diseases, the proportion of immunized adults in our country is frankly deficient. Multiple barriers contribute to perpetuating this problem, within which the lack of prescription of the same by professionals who care for vulnerable populations occupies a central place. Patients with cardiovascular disease represent a particularly risky subpopulation. The spectrum of pathologies that can trigger respiratory infections is wide: development or worsening of heart failure, arrhythmias, acute coronary syndromes and cerebrovascular diseases, among the main ones. The role of immunoprophylaxis with influenza, pneumococcal and tetanus vaccine in patients with different heart diseases is addressed here, evaluating the evidence supporting its use, and placing special emphasis on practical aspects of its use, such as adverse effects, contraindications and special care situations, such as congenital heart disease in adults, heart transplantation, anticoagulation or egg allergy. Thus, this document aims to assist in decision-making for any doctor involved in the care of patients with cardiovascular disease.

Las enfermedades cardiovasculares ocupan la primera causa de muerte en la mayoría de las regiones del mundo, seguidas habitualmente por las enfermedades infecciosas. Desde hace décadas se conoce que las infecciones en general, y particularmente las que involucran el aparato respiratorio, se vinculan con un incremento en el riesgo de eventos cardiovasculares y cerebrovasculares, y su consecuente morbimortalidad. Si bien las vacunas constituyen una excelente estrategia en la prevención de enfermedades infectocontagiosas, la proporción de adultos inmunizados en nuestro país es francamente deficitaria. Múltiples barreras contribuyen a perpetuar esta problemática, dentro de las cuales la falta de prescripción de las mismas por parte de los profesionales que atienden a poblaciones vulnerables ocupa un lugar central. Los pacientes con enfermedades cardiovasculares representan una subpoblación de particular riesgo. El espectro de enfermedades que pueden originar las infecciones respiratorias es amplio: desarrollo o empeoramiento de insuficiencia cardíaca, arritmias, síndromes coronarios agudos y enfermedades cerebrovasculares, entre los principales. Se aborda aquí el rol de la inmunoprofilaxis con vacuna antigripal, antineumocócica y antitetánica en pacientes con diferentes cardiopatías, valorando la evidencia que respalda su empleo y haciendo especial hincapié en aspectos prácticos de su utilización, como efectos adversos, contraindicaciones y situaciones especiales de atención: cardiopatías congénitas del adulto, trasplante cardíaco, individuos anticoagulados o con alergia al huevo. Así, este documento tiene como objetivo asistir en la toma de decisiones a cualquier médico involucrado en el cuidado de pacientes con enfermedad cardiovascular.

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Resumen Las enfermedades cardiovasculares ocupan la primera causa de muerte en la mayoría de las regiones del mundo, seguidas habitualmente por las enfermedades infecciosas. Desde hace décadas se conoce que las infecciones en general, y particularmente las que involucran el aparato respiratorio, se vinculan con un incremento en el riesgo de eventos cardiovasculares y cerebrovasculares, y su consecuente morbimortalidad. Si bien las vacunas constituyen una excelente estrategia en la prevención de enfermedades infectocontagiosas, la proporción de adultos inmunizados en nuestro país es francamente deficitaria. Múltiples barreras contribuyen a perpetuar esta problemática, dentro de las cuales la falta de prescripción de las mismas por parte de los profesionales que atienden a poblaciones vulnerables ocupa un lugar central. Los pacientes con enfermedades cardiovasculares representan una subpoblación de particular riesgo. El espectro de enfermedades que pueden originar las infecciones respiratorias es amplio: desarrollo o empeoramiento de insuficiencia cardíaca, arritmias, síndromes coronarios agudos y enfermedades cerebrovasculares, entre los principales. Se aborda aquí el rol de la inmunoprofilaxis con vacuna antigripal, antineumocócica y antitetánica en pacientes con diferentes cardiopatías, valorando la evidencia que respalda su empleo y haciendo especial hincapié en aspectos prácticos de su utilización, como efectos adversos, contraindicaciones y situaciones especiales de atención: cardiopatías congénitas del adulto, trasplante cardíaco, individuos anticoagulados o con alergia al huevo. Así, este documento tiene como objetivo asistir en la toma de decisiones a cualquier médico involucrado en el cuidado de pacientes con enfermedad cardiovascular.

Abstract Cardiovascular diseases are the leading cause of death in most regions of the world, usually followed by infectious diseases. For decades, infections in general, and particularly those involving the respiratory system, have been known to be associated with an increased risk of cardiovascular and cerebrovascular events, and their consequent morbidity and mortality. Although vaccines are an excellent strategy in the prevention of infectious diseases, the proportion of immunized adults in our country is frankly deficient. Multiple barriers contribute to perpetuating this problem, within which the lack of prescription of the same by professionals who care for vulnerable populations occupies a central place. Patients with cardiovascular disease represent a particularly risky subpopulation. The spectrum of pathologies that can trigger respiratory infections is wide: development or worsening of heart failure, arrhythmias, acute coronary syndromes and cerebrovascular diseases, among the main ones. The role of immunoprophylaxis with influenza, pneumococcal and tetanus vaccine in patients with different heart diseases is addressed here, evaluating the evidence supporting its use, and placing special emphasis on practical aspects of its use, such as adverse effects, contraindications and special care situations, such as congenital heart disease in adults, heart transplantation, anticoagulation or egg allergy. Thus, this document aims to assist in decision-making for any doctor involved in the care of patients with cardiovascular disease.

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The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a nonencapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for bacterial vaccine production. Batch, fed-batch, and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least a fourfold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by western blot and animal immunization assays, indicating that so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole-cell vaccine production, as it can be integrated to the cell separation process keeping the same vaccine quality.

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The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a nonencapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for bacterial vaccine production. Batch, fed-batch, and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least a fourfold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by western blot and animal immunization assays, indicating that so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole-cell vaccine production, as it can be integrated to the cell separation process keeping the same vaccine quality.

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Introducción: La meningitis bacteriana aún constituye un importante problema de salud mundial. En Cuba hay limitadas investigaciones con una perspectiva histórica de esta temática. Objetivo: Describir el comportamiento de la meningitis bacteriana en Cuba (siglo XIX-XXI). Material y Métodos: Estudio descriptivo (corte histórico) entre finales de 1800 y 2017, utilizando el método histórico-lógico y un análisis deductivo-inductivo de múltiples fuentes bibliográficas. Desarrollo: La primera alusión a la meningitis bacteriana en Cuba data de 1877. También se sugiere su probable importación por el ejército de ocupación norteamericano en 1899. En 1901 se aisló el meningococo de Weichselbaum del líquido cefalorraquídeo, lo que constituye, probablemente, su primera notificación en Cuba. Iniciado el siglo XX, se reportan casos aislados y brotes hasta 1976 cuando inicia la mayor epidemia de Enfermedad Meningocócica (serogrupos C y B). En 1979 se vacuna contra el C. En 1980 se implementa una vigilancia epidemiológica especial. Se desarrolla la vacuna cubana VA-MENGOC-BC® (1984) que se usa masivamente (1987) y se contribuye al control, incluyéndose en el Programa Nacional de Inmunizaciones (1991). Haemophilus Influenzae pasa a ser la principal bacteria causante de meningitis bacteriana hasta 1999 en que se aplican vacunas (Vaxem-Hib® y QuimiHib®) y se controla. Su nicho ecológico es ocupado por neumococo hasta ahora. Conclusiones: Desde fines del siglo XIX hasta la segunda mitad del XX la meningitis bacteriana en Cuba se manifestaba como casos aislados y brotes. Durante y después de una gran epidemia, se implementan estrategias preventivas efectivas, incluidas dos vacunas cubanas contra estas enfermedades, que revierten el comportamiento a endemia muy baja hasta la actualidad.

Introduction: Bacterial meningitis remains an important health problem worldwide. In Cuba, there are limited research studies about this issue from a historical perspective. Objective: To describe the behavior of this disease in Cuba (19th - 21st centuries). Material and Methods: A descriptive historical study was carried out between the ends of 1800-2017, using the historical-logical method and a deductive-inductive analysis of multiple bibliographical sources. Development: The first reference to bacterial meningitis in Cuba was made in 1877. The probable introduction of the disease by the US occupation army in 1899 is also considered. In 1901, the meningococci of Weichselbaum was isolated from cerebrospinal fluid, which was probably it first report in Cuba. At the beginning of the 20th century, isolated cases and outbreaks were reported until 1976, when the biggest and larger invasive meningococcal disease began (serogroups C, B). Vaccination against serogroup C started in 1979. In 1980, a special epidemiological surveillance was implemented. The Cuban vaccine VA-MENGOC-BC® against the disease was developed in 1984, which was massively used in 1987. The vaccine contributed to the control of the disease and was included in the National Immunization Program in 1991. Haemophilus Influenzae became the main causative bacterial agent of meningitis until 1999, when the implementation of massive vaccination (Vaxem-Hib® and QuimiHib®) controlled disease. Up to the present, its ecological niche is occupied by pneumococci. Conclusions: From the end of the 19th century to the second half of the 20th century, bacterial meningitis in Cuba behaved as isolated cases and outbreaks. Effective preventive strategies were implemented during and after a huge epidemic, including Cuban vaccines against the disease, that pass on its behavior to a very low endemic disease up to the moment.

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BACKGROUND: Pneumococcal infections are a leading global cause of morbidity and mortality, complicated by the increasing antimicrobial resistance of pneumococcal isolates. OBJECTIVE: To evaluate morbidity and mortality associated with both invasive pneumococcal disease (IPD) and non-IPD in Jamaica in both the paediatric and adult population. Pneumococcal isolates (n= 94) were collected over a 2-year period (2008-2009). METHODS: Risk factors for poor clinical outcomes: death, complicated disease and length of hospitalization (LOH) were evaluated and antimicrobial resistance patterns were determined by Kirby-Bauer disc diffusion. RESULTS: The case fatality rate was 6.8%. Independent mortality risk factors included complicated disease [OR 30.9 (3.4-276.6)] and diabetes mellitus [OR 8.3 (1.4-48.8)]. Independent risk factors for the development of complicated disease included sickle cell disease [OR 36.5 (4.2-320.3)] and sepsis [OR 3.5 (1.2-10.4)]. The LOH was increased most in patients with invasive disease (4.6-fold) and resistance to ceftriaxone (4.3-fold). Penicillin (16.0%) and erythromycin (14.9%) resistance was most prevalent, while ceftriaxone (4.3%) resistance was least prevalent. CONCLUSIONS: The high burden of IPD in at-risk groups in our population and the associated increase in morbidity and mortality underlie the need for improved preventive and therapeutic management strategies in these patients.

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RESUMO Objetivo A pneumonia pneumocócica é uma causa significativa de morbimortalidade entre adultos. Desta maneira, o objetivo principal deste estudo foi avaliar a mortalidade intra-hospitalar e os custos relacionados à doença adquirida em adultos. Métodos Este estudo transversal utilizou prontuários de pacientes adultos com pneumonia pneumocócica internados em um hospital universitário no Brasil, de outubro de 2009 a abril de 2017. Todos os pacientes com idade ≥ 18 anos e diagnosticados com pneumonia pneumocócica foram incluídos. Dados como os fatores de risco, a internação em unidade de terapia intensiva, o tempo de internação, a mortalidade hospitalar e os custos diretos e indiretos foram analisados. Resultados No total, 186 pacientes foram selecionados. A taxa média de mortalidade intra-hospitalar foi de 18% para adultos com idade < 65 anos e 23% para os idosos (≥ 65 anos). A pneumonia pneumocócica bacterêmica acometeu 20% dos pacientes em ambos os grupos, principalmente por doença respiratória crônica (OR ajustada: 3,07; IC95%: 1,23‐7,65; p < 0,01). Após levantamento das internações ocorridas no período de sete anos de tratamento, verificou-se que os custos diretos e indiretos totais anuais foram de US$ 28.188 para adultos < 65 anos (US$ 1.746 per capita) e US$ 16.350 para os idosos (US$ 2.119 per capita). Conclusão A pneumonia pneumocócica continua sendo uma importante causa de morbimortalidade entre adultos, afetando significativamente os custos diretos e indiretos. Esses resultados sugerem a necessidade de estratégias de prevenção para todos os adultos, especialmente para pacientes com doenças respiratórias crônicas.

ABSTRACT Objective Pneumococcal pneumonia is a significant cause of morbidity and mortality among adults. The study's main aim was to evaluate the in-hospital mortality and related costs of community-acquired pneumococcal pneumonia in adults. Methods This cross-sectional study used medical records of adult patients with pneumococcal pneumonia hospitalized in a university hospital in Brazil from October 2009 to April 2017. All patients aged ≥ 18 years diagnosed with pneumococcal pneumonia were included. Risk factors, intensive care unit admission, length of hospital stay, in-hospital mortality, and direct and indirect costs were analyzed. Results In total, 186 patients were selected. The mean in-hospital mortality rate was 18% for adults aged < 65 years and 23% for the elderly (≥ 65 years). Bacteremic pneumococcal pneumonia affected 20% of patients in both groups, mainly through chronic respiratory disease (adjusted OR: 3.07, 95% CI: 1.23-7.65, p < 0.01). Over 7 years, annual total direct and indirect costs were USD 28,188 for adults < 65 years (USD 1,746 per capita) and USD 16,350 for the elderly (USD 2,119 per capita). Conclusion Pneumococcal pneumonia remains an important cause of morbidity and mortality among adults, significantly affecting direct and indirect costs. These results suggest the need for prevention strategies for all adults, especially for patients with chronic respiratory diseases.

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INTRODUCTION: Pneumococcal infections are a public health problem in older adults. In Chile there are two vaccines at this time, PPSV23 and PCV13. The first has lower immunogenicity and effectiveness in preventing pneumococcal pneumonia and a lower cost than PCV13. OBJECTIVE: To determine the cost-effectiveness of PCV13 versus PPSV23 in adults 18 years old and over in the Chilean Health System. MATERIAL AND METHOD: A cost-utility study was performed using the Markov model (population data for a time horizon of 10 years). Utilities and epidemiological data were obtained from the literature and costs from the Chilean Public sector. Vaccine's costs and quality-adjusted life years (QALYs) were determined and compared. RESULTS: PCV13 vaccination program in adults (≥18 years), generated savings of $42,195 USD and an increase of 6,820 QALYs, avoiding 107 cases of bacteremia, 13 meningitis, 6,706 inpatient pneumonia, 4,509 outpatient pneumonia and 1,189 deaths compared to PPSV23 without variation on sensitivity analysis on high impact variables. For the subgroup of patients over 65 years old PCV13 generates savings of $ 32,105.94USD and produces 5,430 QALYs more compared to PPSV23. CONCLUSION: PCV13 is dominant. A PCV13 vaccination program saves costs to the public system, reduces mortality and morbidity; these results are robust.

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