Impact of PCV10 on pediatric pneumococcal disease burden in Brazil: time for new recommendations?

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.

Meningite bacteriana: uma revisão / Bacterial meningitis: a review

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.

Inmunizaciones en adultos con cardiopatías. Resumen del consenso de la Sociedad Argentina de Cardiología / Immunizations in adults with cardiovascular disease. Summary of the Consensus of the Argentine Cardiology Society

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.

Socio-demographic Determinants of Vaccine Coverage for Pneumococcus and Rotavirus among under Five Children in Busolwe Town Council, Butaleja District, Eastern Uganda: A Cross Sectional Study

Background and Aims:There is a high burden of vaccine-preventable diseases in the children under five years of age, particularly pneumonia diarrhea and which is greatly affected by low immunization coverage despite the existing efforts and policies. This study was carried out in Butaleja district and was aimed at establishing the socio-demographic determinants of vaccine coverage for pneumococcus and rotavirus among under five children (U5C) in the district. Study Design:This was a mixed methods cross-sectional study.Place and Duration of Study:Busolwe Town Council, Butaleja District, Eastern Uganda.Methodology:Structured researcher administered questionnaires were administered to 434 caregivers of U5C in different parts of Butaleja district. In-depth interviews with key informants and focused group discussions with Village Health Teams and community members were conducted. Review of Health Management Information Systems records was done. STATA 15 was used to analyze the data.Results:The study found that there is a declining trend in completion of the doses of Pneumococcal vaccine (PCV) and Rotavirus vaccine. For example, in quarter 1 of 2019, out of the 312 children who started immunization, only 2 completed Rota virus immunization and only 117 completed PCV vaccinations a trend that has been observed since 2016. The factors that showed a significant association with the the fact that they gave their child at least one dose of the vaccinewere having been sensitized on the current immunisation schedule(P-value = <0.001), misunderstanding that vaccine is harmful for child(P-value = 0.007), willingness to take children to vaccination(P-value = <0.001), and social factors such as family (P-value = <0.030). Gender also played a key determinant role where the children’s fathers lacked knowledge on significance of immunization and thus discouraged the mothers from taking the children for immunization. Inadequate funding was also highlighted from the Focus Group Discussions.Conclusion:Vaccine coverage for pneumococcus and rotavirus is still low in Butaleja district mainly due to the attitudes and perceptions of caregivers as well as the knowledge gap. There is need forextensive sensitization of all community members to enable them understand the significance of immunization. It would further be important to increase the funding of the immunization programme to intensify and ensure effectual outreaches as well as the establishment and enforcement of a policy for immunization compliance.

Effect of Different Doses of Inhaled Corticosteroids on the Isolation of Nasopharyngeal Flora in Children with Asthma

Objectives: To find the effects of inhaled corticosteroids and the impact of different doses ofinhaled corticosteroids on the isolation of nasopharyngeal flora in asthmatic children aged 1-15 years. Methods: The study included 75 children with asthma and 25 age-matchedcontrols. Nasopharyngeal swabs were obtained. Bacteria were identified by standardtechniques. Results: Pathogenic organisms were isolated from 36% of asthmatic childrenand 20% of controls, the difference was not significant statistically (OR=2.25, 95% CI=0.75-6.67, P=0.13). There was no statistically significant association of using a high dose ofinhaled corticosteroids with the isolation of pathogenic organisms. Usage of biomass fuel forcooking in the household of asthmatic children increases the risk of colonization (OR=3.4,95% CI= 1.26-9.10, P=0.03). Conclusion: Inhaled corticosteroids are safe in the treatmentof asthma and there is no association between different doses of Inhaled corticosteroids andisolation of the pathogenic organism.

Historia de la meningitis bacteriana en Cuba: siglo XIX al XXI

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.

Mortalidade e custos da pneumonia pneumocócica em adultos: um estudo transversal / Mortality and costs of pneumococcal pneumonia in adults: a cross-sectional study

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.

Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia

Background & objectives: Streptococcus pneumoniae (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia. Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated. Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F. Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

Analysis of serotype and clinical manifestation of 80 children with invasive pneumococcal disease in Suzhou / 中国小儿急救医学

Objective To understand serotypes and clinical manifestation of children with invasive pneumococcal disease (IPD) in Suzhou,so as to find a better strategy for reducing the incidence and mortality of IPD. Methods Eighty children with IPD were enrolled into our study from January 2011 to December 2015. The data of epidemiology,serotype,clinical manifestation,laboratory results and prognosis were collected and analyzed. Results The mortality of 80 children with IPD was 17. 5%(14/80). Sixty percent of them were younger than 2 years old,and 78. 6% of 14 dead cases were younger than 2 years old,the median age of dead group 0. 68 (0. 45,2. 07) years was younger than 1. 61 (0. 85,3. 45) years of survival group ( P <0. 05). The incidence rates of hyperpyrexia,vomiting and somnolence in dead group were higher than those in survival group before admission ( P <0. 05), the incidence rates of shock, DIC, respiratory failure, AKI, seizure or coma in dead group were higher than those in survival group ( P<0. 05). The coincidence rate between choice of antibiotics before admission and drug sensitivity test was 15. 0%(12/80),the mortality of coincident group (coincidence between choice of antibiotics and drug sensitivity test) 8. 3% was lower than 16. 2% of non-coincident group with no statistical differences ( P>0. 05). The drug resistance rates of 80 pneumococcus to Erythromycin,Clindamycin,Tetracycline,Sulfamethoxazole,Penicillin,Cefotaxime,Amoxi-cillin,Chloramphenicol,Vancomycin and Levofloxacin were 100% (80/80),98. 8% (79/80),88. 8%(71/80),71. 3%(57/80),48. 8%(39/80),32. 5%(26/80),8. 8%(7/80),5. 0%(4/80),0(0/80) and 0(0/80) respectively. Eight serotypes of 80 IPD cases were listed in descending order:6B(25. 5%,20/80),14 (23. 8%,19/80),19F(15. 0%,12/80),19A(15. 0%,12/80),23F(8. 8%,7/80),20(5. 0%,4/80),9V (5. 0%,4/80) and 15B/C(2. 5%,2/80),and 6 serotypes of 14 dead cases were:6B(35. 7%,5/14),14 (28. 6%,4/14),19F(14. 3%,2/14),19A(7. 1%,1/14),23F(7. 1%,1/14) and 20(7. 1%,1/14); the coverage of IPD serotypes of 7-valent pneumococcal conjugate vaccine (PCV7) 77. 5%(62/80) was lower than 92. 5%(74/80) of 13-valent pneumococcal conjugate vaccine (P <0. 05). Conclusion Majority of dead cases of IPD is always younger than 2 years. The low coincidence rate of choices of antibiotics to inva-sive pneumococcus outpatient and low rate of PCV immunization in China are responsible for the high mortal-ity of IPD. Timely recognition of continuous hyperpyrexia, vomiting and somnolence in early stage and appropriate use of antibiotics is the key to improve the outcome of IPD. Thirteen-valent pneumococcal conju-gate vaccine immunization provides a robust strategy for reducing the incidence and mortality of IPD.

Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections / 영남의대학술지

Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor (TGF)-β1, are involved in different stages of the progression of pneumococcal infection. TGF-β1 is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of TGF-β1 on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of TGF-β1 on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

PURPOSE: Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. MATERIALS AND METHODS: During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. RESULTS: A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. CONCLUSION: PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly.

Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections / 영남의대학술지

Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor (TGF)-β1, are involved in different stages of the progression of pneumococcal infection. TGF-β1 is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of TGF-β1 on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of TGF-β1 on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

Interleukin-1beta Participates in the Development of Pneumococcal Acute Lung Injury and Death by Promoting Alveolar Microvascular Leakage

Streptococcus pneumoniae (S. pneumoniae, also known as pneumococcus) infections are major causes of death worldwide. Despite the development and use of effective antibiotics, high, early mortality due to pneumococcal infections has not been decreased for the last few decades. Recent study found a deadly hemorrhagic acute lung injury (ALI) as a major cause of death at the early stage of severe pneumococcal infections. Interleukin (IL)-1beta was known to play critical roles not only for the development of ALI but also resolution of it. The role of IL-1beta on the pathogenesis of pneumococcal ALI, however, has not been well understood yet. This study aims to investigate the role of IL-1beta on the development of pneumococcal ALI and subsequent death. IL-1beta expression was upregulated in the lungs of pneumococcal ALI in wild-type (WT) mice, but not in the plasma. Despite an increased expression of pulmonary IL-1beta, no inflammatory cell infiltration into airway has been observed. Upregulation of IL-1beta expression was indeed dependent on pneumococcal cytoplasmic toxin pneumolysin and its cell surface receptor Toll-like receptor 4. Deficiency of IL-1R1, a cell surface receptor of IL-1beta, resulted in a markedly reduced hemorrhagic pulmonary edema and early death in pneumococcal ALI. Finally, IL-1beta neutralization in WT mice protects against pulmonary hemorrhagic edema and death. These data suggest that pulmonary expression of IL-1beta exacerbates pneumolysin-induced ALI and death by promoting alveolar hemorrhagic edema.

Distribution of Serotypes and Antibiotic Susceptibility Patterns Among Invasive Pneumococcal Diseases in Saudi Arabia

BACKGROUND: Streptococcus pneumoniae causes life-threatening infections such as meningitis, pneumonia, and febrile bacteremia, particularly in young children. The increasing number of drug-resistant isolates has highlighted the necessity for intervening and controlling disease. To achieve this, information is needed on serotype distribution and patterns of antibiotic resistance in children. METHODS: All cases of invasive pneumococcal disease (IPD) in children aged less than 15 yr recorded at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, were reviewed for serotyping and antibiotic susceptibility. Isolates were collected from 78 consecutive patients with IPD between 2009 and 2012. All collected isolates were subjected to serotyping by co-agglutination, sequential multiplex PCR, and single PCR sequetyping as previously described. RESULTS: The most frequently isolated IPD serotypes were 23F, 6B, 19F, 18C, 4, 14, and 19A, which are listed in decreasing order and cover 77% of total isolates. The serotype coverage for the pneumococcal conjugate vaccine (PCV)7, PCV10, and PCV13 was 77%, 81%, and 90%, respectively. Results from sequential multiplex PCR agreed with co-agglutination results. All serotypes could not be correctly identified using single PCR sequetyping. Minimum inhibitory concentration showed that 50 (64%) isolates were susceptible to penicillin, whereas 70 (90%) isolates were susceptible to cefotaxime. CONCLUSIONS: The most common pneumococcal serotypes occur with frequencies similar to those found in countries where the PCV has been introduced. The most common serotypes in this study are included in the PCVs. Addition of 23A and 15 to the vaccine would improve the PCV performance in IPD prevention.

The in vivo and in vitro Roles of Epithelial Pattern Recognition Receptors in Pneumococcal Infections

Streptococcus pneumoniae, also called pneumococcus, is a major cause of infectious disease in human. Pneumococcus resides in the nasopharynx as an upper respiratory commensal, and most of pneumococcal colonizations are asymptomatic in immunocompetent individuals. When nasopharyngeal mucosal homeostasis is disrupted, pneumococcus migrates into middle ear and lower respiratory tract and causes detrimental colonization. In this regard, the epithelial cells of middle ear and lung act as first line of defense against pneumococcus to prevent invasive pneumococcal diseases. Respiratory epithelial cells express various cell-surface and intra-cellular receptors sensing microbial pathogens and respond to sensed pathogens by triggering intra-cellular signaling pathways and inducing pathogen-specific innate immune responses. Various epithelial cell-surface and intra-cellular receptors, such as Toll-like receptors (TLRs), Nod-like receptors (NLRs), intracellular DNA sensing receptors, and scavenger receptors (SRs), participate in sensing of pneumococcus, and the activation of these receptors by pneumococcal components induces anti-pneumococcal innate immune responses including epithelial apoptosis and inflammatory cytokine/chemokine expressions. Epithelial sensing of pneumococcus is a critical step for setting an early defense against pneumococcal infection, and also is required to recruit and activate innate immune cells and trigger adaptive immunity.

Antibody Responses in Hematopoietic Cell Transplantation Recipients after Vaccination Against Haemophilus Influenzae Type b and Streptococcus pneumoniae / 소아감염

PURPOSE: Hematopoietic cell transplantation (HCT) recipients are vulnerable to invasive infection by Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). This study was performed to evaluate immune responses after Hib and Sp vaccination in Korean pediatric HCT recipients. METHODS: Patients were prospectively enrolled at Samsung Medical Center during 2009-2011. ELISA tests to detect anti-PRP IgG antibody and antibodies to Sp serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were performed at the Center for Vaccine Evaluation and Study, Ewha Medical Research Institute. RESULTS: Ten patients (two allogeneic, eight autologous recipients) with median age 5.4 years (range 2.7-12.2 years) were enrolled. Before Hib vaccination, 60% of patients' anti-PRP IgG titers were below 0.15 microg/mL. After vaccination, 100% of patients' anti-PRP IgG titers increased above 0.15 microg/mL (cut-off value for detection) and 1.0 microg/mL (cut-off value for seroprotection). For pneumococcus, in 2-5 year-old patients, pre-vaccination geometric mean concentrations (GMCs) of IgG for six serotypes (4, 6B, 9V, 14, 18C, and 23F) were below 0.35 microg/mL and at 5 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 microg/mL. In patients older than 5 years, pre-vaccination GMCs of IgG for four serotypes (4, 9V, 14, and 23F) were below 0.35 microg/mL and at 3 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 microg/mL. CONCLUSION: Most HCT recipients had low or no protective antibodies to Hib and Sp before vaccination, but showed good immune responses to protective levels after vaccination.

Deficiência específica de anticorpo antipolissacarídeo de pneumococo e resposta humoral a vacinas pneumocócicas: atualização em diagnóstico / Specific anti-pneumococcal polysaccharide antibody deficiency and humoral response to pneumococcal vaccines: uptdate on diagnosis

A deficiência específica de anticorpo antipolissacarídeo de pneumococo é o comprometimento da resposta IgG específica aos antígenos polissacarídeos do pneumococo e manifesta-se de maneira semelhante às outras deficiências de imunoglobulinas, com infecções recorrentes do trato respiratório. A prevalência é variável, entre 7 a 19%, representando no Brasil 8,7% dos casos de imunodeficiências. O diagnóstico funcional baseia-se na capacidade do organismo montar uma resposta imune constituída pela produção de anticorpos quando estimulado por antígenos polissacarídeos presentes na vacina pneumocócica polissacarídea pura. No estudo da resposta à vacina pneumocócica polissacarídea pura é necessário testar os sorotipos não comuns à vacina polissacarídea conjugada para determinar a resposta de anticorpos antipolissacarídeos sem a interferência de anticorpos antiproteínas advindos da vacina polissacarídea conjugada. São reconhecidos quatro diferentes fenótipos da doença, denominados memória, leve, moderada e grave. O objetivo do presente trabalho foi realizar revisão da literatura para verificar a epidemiologia, diagnóstico e fenótipos da deficiência específica de anticorpo antipolissacarídeo de pneumococo. Trata-se de revisão narrativa de artigos nos últimos 10 anos sobre a deficiência de anticorpo específica para o pneumococo. Concluímos que a deficiência específica de anticorpo antipolissacarídeo de pneumococo é frequente, com espectro laboratorial variável.

Specific anti-pneumococcal polysaccharide antibody deficiency is characterized by impairment of specific IgG response to pneumococcal polysaccharide antigens. Its clinical manifestation is similar to other immunoglobulin deficiencies, with recurrent infections of the respiratory tract. Prevalence is variable, ranging from 7 to 19%; in Brazil, it accounts for 8.7% of cases of immunodeficiencies. Diagnosis is based on the body’s functional ability to mount an immuneresponse including the production of antibodies after stimulation by polysaccharide antigens present in the pure pneumococcal polysaccharide vaccine. When studying responses to this vaccine, it is necessary to test serotypes other than those present in the pneumococcal conjugate vaccine, in order to determine the response of anti-polysaccharide antibodies not influenced by antiprotein antibodies originating from the conjugate vaccine. Four different phenotypes of the disease are known: memory, mild, moderate, and severe. The objective of the present study was to review the literature on the epidemiology, diagnosis, and phenotypes of specific antipolysaccharide antibody deficiency. This narrative review includes papers published in the past 10 years on specific anti-pneumococcal polysaccharide antibody deficiency. We conclude that the condition is common, with a variable spectrum of laboratory findings.

Cobertura de vacunación en adultos y adultos mayores en México / Vaccination coverage in young, middle age and elderly adults in Mexico

Objetivo. Estimar la cobertura y el porcentaje de vacunación en adultos mayores de 20 años. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2011-2012. Resultados. En adultos de 20 a 59 años las coberturas de esquema completo, vacuna doble viral (SR) y vacuna antitetánica y antidiftérica (Td) fue de 44.7, 49.0 y 67.3%, respectivamente. En los esquemas evaluados, tanto la cobertura como el porcentaje de vacunación fueron significativamente mayores en mujeres que en hombres. En las mujeres de 20 a 49 años, la cobertura de esquema completo, SR y Td fue de 48.3, 53.2 y 69.8%, respectivamente. En el caso de los adultos de 60 a 64 años de edad, la cobertura de esquema completo, Td y anti-influenza fue de 46.5, 66.2 y 56.0%, respectivamente. Las coberturas para los adultos de los 65 años o más fueron para esquema completo, Td, anti-influenza y antineumococo con 44.0, 69.0, 63.3 y 62.0% , respectivamente. Conclusión. Las coberturas de vacunación en adultos están por debajo de los valores óptimos aunque es posible que estén subestimadas. Se proponen recomendaciones para mejorarlas.

Objective. To estimate vaccination coverage in adults 20 years of age and older. Materials and methods. Analysis of data obtained from the National Health and Nutrition Survey 2012. Results. Among adults 20-59 years old coverage with complete scheme, measles and rubella (MR) and tetanus toxoid and diphtheria toxoid (Td) was 44.7,49. and 67.3%, respectively. Coverage and percentage of vaccination were significantly higher among women than men. Among women 20-49 years coverages with complete scheme, MR and Td were 48.3, 53.2 and 69.8%, respectively. Among adults 60-64 years old, coverage with complete scheme, Td and influenza vaccine were 46.5, 66.2 and 56.0%, respectively. Among adults >65 years coverages for complete scheme, Td, influenza vaccine and pneumococcal vaccine were 44.0, 69.0, 63.3 and 62.0%, respectively. Conclusion. Vaccination coverage among adult population as obtained from vaccination card or self-report is below optimal values although data may be underestimated. Recommendations for improvements are proposed.

A Case of Bilateral Knee Septic Arthritis Caused by Pneumococcal Bacteremia / 대한구급학회지

Pneumococcus can cause pneumonia, sinusitis, infective endocarditis, meningitis and primary bacteremia. However, few reports in the literature show bilateral septic arthritis with pneumococcal bacteremia. We report on a case of a 78-year old woman who presented with fever, pain and swelling in both knees. Both knee fluid aspirates were purulent with thick viscosity, and the gram stain revealed gram positive cocci in chains. The patient underwent emergent washing and arthroscopic debridement, followed with empirical antibiotics treatment. Two out of two blood cultures were positive for penicillin-susceptible Streptococcus pneumonia. Synovial fluid cultures were also positive for S. pneumoniae. The patient was treated with intravenous ceftriaxone for 4 weeks. Bilateral knee septic arthritis with pneumococcal bacteremia is rarely reported. Here we report on the case with a review of the literature.

Utilización de la penicilina en la infección extrameníngea por Streptococcus pneumoniae / Use of penicillin in the extrameningeal infection from Streptococcus pneumoniae

La resistencia del Streptococcus pneumoniae a los antibióticos betalactámicos es relativa, y puede ser superada si se incrementa la dosis de esta clase de medicamentos. La definición de susceptibilidad y resistencia del Streptococcus pneumoniae se creó originalmente para predecir respuesta al tratamiento de la infección del sistema nervioso central. La infección fuera del sistema nervioso central por la mayoría de las cepas de S. pneumoniae responde a las dosis habituales de antibióticos betalactámicos. Se realiza una revisión de los nuevos puntos de corte del Laboratory Standars Institute para sensibilidad a penicilina del patógeno, y se analiza su implicación en la terapéutica actual de la enfermedad extrameníngea por S. pneumoniae

The beta-lactamase resistance of Strepcoccus pneumoniae is relative and may to be overcome if the dose of this type of drugs is increased. The definition of oversensitivity and of resistance of above mentioned bacteria was originally created to predict the infection response of central nervous system (CNS) to treatment. The infection outside of the CNS by most of strains of S. pneumoniae responds to habitual dose of betalactamic antibiotics. A review of the new cut points of Laboratory Standards Institute for the sensitivity to pathogen penicillin and its implication in current therapy of extrameningeal disease by S. pneumoniae is analyzed