Invasive Pneumococcal Disease Characterization in Adults and Subgroups aged < 60 years and ≥ 60 years in Bogota, Colombia.

Background: There is scarce information on the burden of invasive pneumococcal disease (IPD) among adults in low- and middle-income countries. This study aimed to describe the clinical outcomes and microbiological characteristics associated with IPD in adults and subgroups aged 18-59 years and ≥60 years in Colombia. Methods: A retrospective chart review study was conducted in five institutions of Bogotá from January 2011 to December 2017. Analyses were carried out for overall population and stratified by age group (18-59; ≥ 60 years). Results: There were 169 IPD cases; median age was 58 years, 51.5% were male, and 80.5% had at least one comorbidity. Bacteremic pneumonia was the most common presentation (63.9%). The median length of hospital stay was 12 days with high healthcare resource utilization (HCRU): 58.6% required ICU and 53.3% inotropic support. Overall case-fatality rate (CFR) was 41.4%. Clinical outcomes were worse in patients ≥60 years old with significantly higher CFR and HCRU (ICU admission, mechanical ventilation, and inotropic support) compared to those aged 18-59 years. The most frequent serotypes were 3, 6 A/C, 14, and 19A. The sensitivity to penicillin in meningitis and non-meningitis isolates were 75% and 89.1% respectively. Conclusions: IPD was associated with a substantial burden in adults and worse clinical outcomes and HCRU in older adults in Colombia. Surveillance data combined with clinical outcomes have the potential to inform age-based pneumococcal vaccination policies.

Nasal Priming with Lactobacillus rhamnosus CRL1505 Stimulates Mononuclear Phagocytes of Immunocompromised Malnourished Mice: Improvement of Respiratory Immune Response.

The effect of Lactobacillus rhamnosus CRL1505 (Lr) on macrophages (Ma) and dendritic cells (DC) in the orchestration of anti-pneumococcal immunity was studied using malnutrition and pneumococcal infection mouse models. Monocytes (Mo), Ma, and DC in two groups of malnourished mice fed with balanced diet (BCD) were studied through flow cytometry; one group was nasally administered with Lr (BCD+Lr group), and the other group was not (BCD group). Well-nourished (WNC) and malnourished (MNC) mice were used as controls.Malnutrition affected the number of respiratory and splenic mononuclear phagocytes. The BCD+Lr treatment, unlike BCD, was able to increase and normalize lung Mo and Ma. The BCD+Lr mice were also able to upregulate the expression of the activation marker MHC II in lung DC and to improve this population showing a more significant effect on CD11b+ DC subpopulation. At post-infection, lung Mo values were higher in BCD+Lr mice than in BCD mice and similar to those obtained in WNC group. Although both repletion treatments showed similar values of lung Ma post-infection, the Ma activation state in BCD+Lr mice was higher than that in BCD mice. Furthermore, BCD+Lr treatment was able to normalize the number and activation of splenic Ma and DC after the challenge.Lr administration stimulates respiratory and systemic mononuclear phagocytes. Stimulation of Ma and DC populations would increase the microbicide activity and improve the adaptive immunity through its antigen-presenting capacity. Thus, Lr contributes to improved outcomes of pneumococcal infection in immunocompromised hosts.

Evolution of cytokines/chemokines in cases with community-acquired pneumonia and distinct etiologies.

AIM: To compare the systemic cytokines/chemokines levels over time during the evolution of children hospitalized with community-acquired pneumonia (CAP) with and without pneumococcal infection. METHODS: Children less than 5-years-old hospitalized with CAP were prospectively investigated in Salvador, Brazil. Clinical data and biological samples were collected to investigate 20 etiological agents and to determine serum cytokines/chemokines levels on admission and 2 to 4 weeks later. Cases with pneumococcal infection received this diagnosis irrespective of also having other etiologies. RESULTS: A total of 277 patients were enrolled, however, serum sample was unavailable for cytokine measurement upon admission (n = 61) or upon follow-up visit (n = 36), etiology was undetected (n = 50) and one patient did not attend the follow-up visit. Therefore, this study group comprised of 129 cases with established etiology. The median (interquartile range) age and sampling interval was 18 (9-27) months and 18 (16-21) days, respectively. Established etiology was viral (52.0%), viral-bacterial (30.2%), and bacterial (17.8%). Pneumococcal infection was found in 31 (24.0%) patients. Overall, median interleukin-6 (IL-6; 10.6 [4.7-30.6] vs 21.0 [20.2-21.7]; P = .03), IL-10 (3.5 [3.1-4.5] vs 20.1 [19.8-20.4]; P < .001), and CCL2 (19.3 [12.4-23.2] vs 94.0 [67.2-117.8]; P < .001) were significantly higher in convalescent serum samples, whereas median CXCL10 (83.6 [36.4-182.9] vs 14.6 [0-116.6]; P < .001) was lower. Acute vs convalescent levels evolution of IL-10, CCL2, and CXCL10 did not differ among patients with or without pneumococcal infection. However, IL-6 decreased (27.8 [12.3-48.6] vs 20.8 [20.2-22.6]; P = .1) in patients with pneumococcal infection and increased (9.0 [4.2-22.6] vs 21.0 [20.2-21.7]; P = .001) in patients without it. CONCLUSION: The marked increase of IL-6 serum levels during the acute phase makes it a potential biomarker of pneumococcal infection among children with CAP.

Systemic cytokines and chemokines on admission of children hospitalized with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the main cause of death in children under-5 years worldwide and Streptococcus pneumoniae is the most common bacterial agent. However, it is difficult to identify pneumococcal infection among children with CAP. We aimed to assess association between any cytokine/chemokine and pneumococcal infection in childhood CAP. Furthermore, we evaluated the diagnostic value of cytokine/chemokine for pneumococcal infection. This prospective study was conducted at an Emergency Room, in Salvador, Brazil. Children <5-years-old hospitalized with CAP in a 21-month period were evaluated. On admission, clinical and radiological data were collected along with biological samples to investigate 20 etiological agents and determine serum cytokines (interleukin (IL)-8, IL-6, IL-10, IL-1ß, IL-12, TNF-α, IL-2, IL-4, IL-5, γ-interferon), and chemokines (CCL2, CCL5, CXCL9, CXCL10) concentration. From 166 patients with etiology detected, pneumococcal infection was detected in 38 (22.9%) cases among which the median IL-6(pg/ml) was 31.2 (IQR: 12.4-54.1). The other 128 cases had other causative agents detected (Haemophilus influenzae, Moraxella catarrhalis, atypical bacteria and viruses) with the median IL-6 concentration being 9.0 (IQR: 4.1-22.0; p < 0.001). The area under the ROC curve for IL-6 to predict pneumococcal CAP was 0.74 (95%CI: 0.65-0.83; p < 0.001). By multivariate analysis, with pneumococcal CAP as dependent variable, IL-6 was an independent predictor for pneumococcal infection (OR = 5.56; 95%CI: 2.42-12.75, cut-off point = 12.5 pg/ml; p = 0.0001). The negative predictive value of IL-6 under 12.5 pg/ml for pneumococcal infection was 90% (95%CI: 82-95%). Independently significant difference was not found for any other cytokines/chemokines. Serum IL-6 concentration on admission is independently associated with pneumococcal infection among children under-5 years hospitalized with CAP.

Prospective evaluation of Streptococcus pneumoniae serum antibodies in patients with primary immunodeficiency on regular intravenous immunoglobulin treatment.

BACKGROUND: This is a prospective study that assessed pneumococcal antibody levels in PID patients under intravenous immunoglobulin (IVIG) treatment using different brands. METHODS: Twenty-one patients receiving regular IVIG every 28 days were invited to participate: 12 with common variable immunodeficiency, six with X-linked agammaglobulinaemia and three with hyper-IgM syndrome. One blood sample was collected from each patient just prior to IVIG administration at a three-month time interval during one year. A questionnaire was filled in with patient's demographic data and history of infections during the study period. Streptococcus pneumoniae antibodies against six serotypes (1, 5, 6B, 9V, 14 and 19F) were assessed by ELISA both in patients' serum (trough levels) and in IVIG samples. RESULTS: Median total IgG trough serum levels were 7.91g/L (range, 4.59-12.20). All patients had antibody levels above 0.35µg/mL to the six serotypes on all four measurements. However, only 28.6% of patients had pneumococcal antibodies for the six analysed serotypes above 1.3µg/mL on all four evaluations during the one-year period. No correlation was found between IgG trough levels and pneumococcal specific antibodies. Eighteen of the 21 patients (85.7%) had infections at some point during the 12-month follow-up, 62/64 (96.9%) clinically classified in respiratory tract infections, four of which were pneumonia. CONCLUSIONS: Pneumococcal antibodies are present in a high range of concentrations in sera from PID patients and also in IVIG preparations. Even maintaining a recommended IgG trough level, these patients can be susceptible to these bacteria and that may contribute to recurrent respiratory infections.

Caracterización de pacientes fallecidos por enfermedad neumocóccica invasiva en la poblacion infantil de Bogotá, Colombia / Characterization of patients who died of invasive pneumococcal disease in the child population of Bogota, Colombia

Introducción: El Streptococcus pneumoniae (S. pneumoniae), también denominado neumococo, es una de las principales bacterias asociadas a mortalidad en menores de 2 años, con una incidencia de morbimortalidad variable de acuerdo a la demografía y exposición a factores protectores o de riesgo. Objetivo: Caracterizar los pacientes fallecidos por enfermedad neumocóccica invasiva (ENI) entre el 2008-2014 en la población infantil de 8 instituciones de salud en Bogotá, Colombia. Pacientes y método: Estudio observacional descriptivo tipo serie de casos, en pacientes fallecidos por ENI, mayores de 28 días hasta los 18 años, en 8 instituciones de tercer nivel de atención en Bogotá, Colombia. Periodo del estudio del 1 de enero de 2008 al 15 de enero de 2014. Tamaño de la muestra: 239 pacientes. Resultados: Se revisaron 239 casos registrados de ENI, presentando una mortalidad del 7,5% (n = 18). La edad promedio de los pacientes que fallecieron fue de 43,7 meses, con un rango de edad entre 2 y 176 meses (14 años); el 66% de los casos era de sexo masculino. Se identificaron serotipos en 8 pacientes, encontrando: 6A, 6B, 10A, 14, 18C, 23B, 23F, 35B. La presentación clínica más frecuente de los casos de mortalidad fue meningitis con el 33% (6 casos), seguida por bacteriemia sin foco en el 28% (5 casos) y neumonía con el 27% (5 casos). Se presentaron situaciones clínicas combinadas como neumonía y meningitis en el 11% (2 casos). Dos de los pacientes tenían factores de riesgo para ENI claramente documentados (asplenia y enfermedad respiratoria crónica). Conclusiones: La mortalidad por ENI es especialmente alta en los menores de 2 años y en pacientes de sexo masculino, especialmente cuando presenta foco meníngeo (44%). La serotipificación no fue posible en todos los pacientes fallecidos, ya que no se envió la cepa aislada al Instituto Nacional de Salud. Se requiere una vigilancia continua y sistemática para evaluar el impacto de la vacunación y las posibles modificaciones en el patrón de presentación de la enfermedad.

Introduction: Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is one of the main bacteria associated with mortality in children under 2 years of age, with a morbidity and mortality incidence that varies according to demographics and exposure to risk, or protective factors. Objective: To describe the child mortality due to invasive pneumococcal disease (IPD) between 2008 -2014 (6 years), in 8 Medical Centres in Bogotá, Colombia. Patients and method: Descriptive observational case series of patients who died of IPD, aged 28 days to 18 years, in 8 tertiary care institutions in Bogota, Colombia. The study period was from 1 January 2008 to 15 January 2014. Sample size: 239 patients. Results: A total of 239 registered cases of IPD were reviewed, showing a mortality of 8% (n 18). The mean age of patients that died was 43.7 months, with an age range from 2 to 176 months (14 years), with 66% of the cases being male. Serotypes were identified in 8 patients, finding: 6A, 6B, 10A, 14, 18C, 23B, 23F, and 35B. The most common clinical presentation of the cases was meningitis with mortality of 33% (6 cases), followed by bacteraemia without focus in 28% (5 cases), and pneumonia with 27% (5 cases). Combined clinical situations were presented, such as pneumonia and meningitis in 11% (2 cases). Two of the patients had clearly documented risk factors for IPD (asplenia and chronic respiratory disease). Conclusions: IPD mortality is particularly high in children under 2 years in male patients, especially when presented with a meningeal focus (44%). Serotyping was not possible in all patients who died, since no strain isolated was sent to the National Institute of Health. Continuous and systematic vigilance is required to evaluate the impact of vaccination and possible changes in the pattern of presentation of disease.

[Characterization of patients who died of invasive pneumococcal disease in the child population of Bogota, Colombia]. / Caracterización de pacientes fallecidos por enfermedad neumocóccica invasiva en la poblacion infantil de Bogotá, Colombia.

INTRODUCTION: Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is one of the main bacteria associated with mortality in children under 2 years of age, with a morbidity and mortality incidence that varies according to demographics and exposure to risk, or protective factors. OBJECTIVE: To describe the child mortality due to invasive pneumococcal disease (IPD) between 2008 -2014 (6 years), in 8 Medical Centres in Bogotá, Colombia. PATIENTS AND METHOD: Descriptive observational case series of patients who died of IPD, aged 28 days to 18 years, in 8 tertiary care institutions in Bogota, Colombia. The study period was from 1 January 2008 to 15 January 2014. SAMPLE SIZE: 239 patients. RESULTS: A total of 239 registered cases of IPD were reviewed, showing a mortality of 8% (n 18). The mean age of patients that died was 43.7 months, with an age range from 2 to 176 months (14 years), with 66% of the cases being male. Serotypes were identified in 8 patients, finding: 6A, 6B, 10A, 14, 18C, 23B, 23F, and 35B. The most common clinical presentation of the cases was meningitis with mortality of 33% (6 cases), followed by bacteraemia without focus in 28% (5 cases), and pneumonia with 27% (5 cases). Combined clinical situations were presented, such as pneumonia and meningitis in 11% (2 cases). Two of the patients had clearly documented risk factors for IPD (asplenia and chronic respiratory disease). CONCLUSIONS: IPD mortality is particularly high in children under 2 years in male patients, especially when presented with a meningeal focus (44%). Serotyping was not possible in all patients who died, since no strain isolated was sent to the National Institute of Health. Continuous and systematic vigilance is required to evaluate the impact of vaccination and possible changes in the pattern of presentation of disease.

Impacto Económico de la Vacuna contra el Neumococo en Pacientes Oncológicos / Economic impact of neumococcal vaccine on oncological patients

Objetivos: Evaluar económicamente la vacuna contra S pneumoniae en pacientes oncológicos para Colombia. Métodos: Dado que la efectividad de la vacuna en este tipo de pacientes no está comprobada, se calculó el costo de los primeros seis años de un programa de vacunación para pacientes oncológicos y se estimó el costo de oportunidad con alternativas de detección temprana de cáncer. Resultados: Un programa de vacunación de pacientes oncológicos contra S pneumoniae costaría en sus primeros seis años cerca de treinta y un mil millones de pesos constantes de 2006. Con estos recursos se podrían realizar aproximadamente 170 000 colonoscopias o pruebas de detección temprana de VPH, 500 000 mamografías o más de 3 800 000 citologías. Conclusiones: Dada la escasez de recursos, es preferible económicamente destinar estas cifras a adelantar programas cuya efectividad esté comprobada, ya sea para detección temprana de cáncer o para vacunación de niños sanos.

Objective: An economic evaluation of an anti-S pneumoniae vaccine for oncological patients in Colombia. Methods: As there is no evidence of vaccine effectiveness for this kind of patient, the cost of a vaccination programme for oncological patients was calculated during its first six years and the opportunity cost was estimated for early cancer detection alternatives. Results: An anti-S. pneumoniae vaccination programme for oncological patients would cost around $31 000 000 000 (Colombian pesos in 2006, i.e. nearly US$12 400 000) during its first years. Alternative programs could be developed with this amount, such as 170 000 colonoscopies or early HPV detection, 500 000 mammographies, or more than 3 800 000 cytologies. Conclusions: Given the scarcity of resources, it would be better (from an economic point of view) to devote this amount to programmes whose effectiveness has been proven, such as early cancer detection or vaccinating healthy children.