Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans.

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005-2019: Observational analysis.

INTRODUCTION: The introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. METHODS: A total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates - ARR) of VTs between the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods. RESULTS: The findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. CONCLUSIONS: Our results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods.

The direct effect of pneumococcal conjugate vaccines on invasive pneumococcal disease in children in the Latin American and Caribbean region (SIREVA 2006-17): a multicentre, retrospective observational study.

BACKGROUND: Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction. METHODS: We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction. FINDINGS: Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p<0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period. INTERPRETATION: SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

[Regional System for Vaccines (SIREVA), laboratory surveillance and vaccine development for Streptococcus pneumoniae: bibliometric analysis, 1993-2019]. / Sistema Regional de Vacunas (SIREVA), vigilancia por laboratorio y desarrollo de vacunas para Streptococcus pneumoniae: análisis bibliométrico, 1993-2019.

OBJECTIVE: To measure through bibliometric analysis the productivity, visibility and impact of the Regional System for Vaccines (SIREVA, a project by the Pan American Health Organization), including its two components laboratory surveillance and vaccine development. METHODS: Publications about laboratory surveillance and vaccine development were recovered from Scopus, including their references and citations, and their bibliometric indicators were analyzed. VOSviewer 1.6.13® was used to visualize the co-authorship networks, by country and authors, and to perform a cooccurrence analysis of terms included in the titles and abstracts of the publications. RESULTS: The criteria for laboratory surveillance and vaccine development were met by 173 and 128 publications, respectively. Ten countries in the Region of the Americas were responsible for 90.8% of the publications on laboratory surveillance and 8 for all publications on vaccine development. The 10 most cited publications on laboratory surveillance and on vaccine development were included in 855 and 503 articles, respectively, the main authors being from Australia, Belgium, Brazil, China, Germany, the United Kingdom and the United States of America. Network building and visualization by author and country co-authors, and co-occurrence of terms showed networking and intraregional collaboration, and allowed for the follow-up of study areas and evolution over time. CONCLUSIONS: The bibliometric analysis allowed to objectively record the productivity and visibility of the Regional System for Vaccines for Streptococcus pneumoniae in the Region.

Sistema Regional de Vacunas (SIREVA), vigilancia por laboratorio y desarrollo de vacunas para Streptococcus pneumoniae: análisis bibliométrico, 1993-2019

[RESUMEN]. Objetivo. Medir a través del análisis bibliométrico la productividad, la visibilidad y el impacto del Sistema Regional de Vacunas (SIREVA, un proyecto de la Organización Panamericana de la Salud) en sus dos componentes, la vigilancia por laboratorio y el desarrollo de vacunas. Métodos. Se recuperaron de Scopus las publicaciones correspondientes a vigilancia por laboratorio y desarrollo de vacunas con sus referencias y citas y se aplicó la herramienta para obtener los indicadores bibliométricos. Se utilizó VOSviewer® 1.6.13 para visualizar las redes de coautoría por país y autores, y para realizar un análisis de coocurrencia de términos incluidos en los títulos y resúmenes de las publicaciones. Resultados. Cumplieron los criterios establecidos para vigilancia por laboratorio y desarrollo de vacunas 173 y 128 publicaciones, respectivamente. Diez países de la Región fueron responsables de 90,8% de las publicaciones sobre vigilancia por laboratorio y 8 países de todas las publicaciones sobre desarrollo de vacunas. Las diez publicaciones más citadas sobre vigilancia por laboratorio y sobre desarrollo de vacunas estaban incluidas en 855 y 503 artículos, respectivamente; los principales autores se encontraban en Alemania, Australia, Bélgica, Brasil, China, Estados Unidos de América y el Reino Unido. La construcción y visualización de redes por coautorías de autores y países, y la coocurrencia de términos mostraron el trabajo en red y la colaboración intrarregional, así como permitieron hacer seguimiento a las diversas áreas de estudio y su evolución en el tiempo. Conclusiones. El análisis bibliométrico permitió documentar de manera objetiva la productividad y visibilidad del Sistema Regional de Vacunas para Streptococcus pneumoniae en la Región.

[ABSTRACT]. Objective. To measure through bibliometric analysis the productivity, visibility and impact of the Regional for Vaccines (SIREVA, a project by the Pan American Health Organization), including its two components laboratory surveillance and vaccine development. Methods. Publications about laboratory surveillance and vaccine development were recovered from Scopus, including their references and citations, and their bibliometric indicators were analyzed. VOSviewer 1.6.13® was used to visualize the co-authorship networks, by country and authors, and to perform a cooccurrence analysis of terms included in the titles and abstracts of the publications. Results. The criteria for laboratory surveillance and vaccine development were met by 173 and 128 publications, respectively. Ten countries in the Region of the Americas were responsible for 90.8% of the publications on laboratory surveillance and 8 for all publications on vaccine development. The 10 most cited publications on laboratory surveillance and on vaccine development were included in 855 and 503 articles, respectively, the main authors being from Australia, Belgium, Brazil, China, Germany, the United Kingdom and the United States of America. Network building and visualization by author and country co-authors, and co-occurrence of terms showed networking and intraregional collaboration, and allowed for the follow-up of study areas and evolution over time. Conclusions. The bibliometric analysis allowed to objectively record the productivity and visibility of the Regional System for Vaccines for Streptococcus pneumoniae in the Region.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean 2010-2015: A systematic review and a time series analysis.

BACKGROUND: This systematic review aims to describe the prevalence, trends, and antibiotic resistance of Streptococcus pneumoniae serotype 19A (Spn19A) that causes invasive and non-invasive diseases in children <5 years in Latin-American and Caribbean countries. METHODS: We searched for published (between January 2010 and February 2016) observational and clinical studies within the region including effectiveness and impact on Spn19A after pneumococcal conjugate vaccine (PCV) introduction. We calculated prevalence estimates by country and standardized the frequency of isolates to conduct an interrupted time series analysis for selected countries and to assess the potential changes in disease trends, overall and for Spn19A. RESULTS: We identified and reviewed full-text of 89 publications and included 59 in the analysis. Data from the laboratory surveillance network, SIREVA, were included in 43 (74%) of the invasive pneumococcal disease reports. There are differences in the sensitivity, representativeness, and heterogeneity of laboratory surveillance. There has been and overall reduction in the trend and number of invasive S. pneumoniae isolates in children <5 years after PCVs introduction. To date, the prevalence of Spn19A has increased, however, there has been no observed change in the trend. CONCLUSIONS: This updated systematic review provides evidence of a reduction in the total number of invasive pneumococcal disease isolates after the introduction of PCVs in the region but cannot yet conclude a change in the trend of Spn19A disease.

Cryptococcosis in Colombia: Compilation and Analysis of Data from Laboratory-Based Surveillance.

The passive and voluntary surveillance of cryptococcosis in Colombia since 1997 has seen an increasing participating rate, revealing its importance to both in immunosuppressed and immunocompetent people. The present work details the national data gathered in 1997-2016, through a retrospective analysis of the information collected in the survey. From a total of 1974 cases reported, an overall incidence of 0.23 cases per 100,000 people was found. This incidence rose to 1.1 cases per 1000 people in the Acquired Immunodeficiency Syndrome (AIDS) population. Cryptococcosis was most common in male young adults (26-40 years), with a male:female ratio of 3.9:1 in the general population and 5.4:1 in Human Immunodeficiency Virus (HIV) patients. Culture was the most common form of diagnosis in 96.3% of cases, recovering C. neoformans species in 87.5% and C. gattii in 3.1% of samples. VNI was the most prevalent (96.1%) molecular type, while VGII predominated in C. gattii isolates (54.3%). Early mortality was reported as the outcome in 47.5% of patients. Cryptococcosis remains an important opportunistic disease in Colombia and is gaining status as a primary pathogen in apparently immunocompetent patients. Our findings show the importance of including cryptococcosis as a notifiable disease, which will allow for improving opportune diagnosis and treatment, resulting in better patient outcomes.

Aislamientos invasivos de Haemophilus influenzae en menores de 5 años: distribución de los serotipos y de la sensibilidad antimicrobiana, SIREVA II Colombia 2002-2013 / Invasive Haemophilus influenzae isolates in children younger than 5 years: Distribution of serotypes and antimicrobial sensitivity, SIREVA II Colombia 2002-2013

Objetivo: Analizar del 2002 al 2013 los datos de la vigilancia de los serotipos y sensibilidad antimicrobiana de los aislamientos invasivos de Haemophilus influenzae ( H. influenzae ) en niños menores de 60 meses. Materiales y métodos: Se analizaron los datos demográficos, fuente y enfermedad asociada de los aislamientos invasivos de H. influenzae recibidos entre 2002 y 2013. Todos los aislamientos habían sido confirmados bacteriológicamente, tenían el dato del serotipo, el cual fue determinado por el método de aglutinación en lámina y PCR y los patrones de sensibilidad antimicrobiana por concentración inhibitoria mínima a ampicilina, SXT, cloranfenicol, cefuroxima y ceftriaxona. El análisis se realizó por periodos de 3 años. Resultados: Por enfermedad invasiva el 50,5% eran de pacientes con meningitis, 23,5% de neumonías, 19,5% de sepsis y bacteriemia, 2,0% de otros y 4,5% sin dato. Por procedencia se recibieron de Bogotá y Antioquia 55 aislamientos de cada uno, de Risaralda 24, de Valle 15, de Santander 11 y 40 de 14 departamentos. El serotipo predominante fue el Hib (40,5%), seguido de HiNT (38,0%), Hia (17,5%), Hid (2,0%), Hif (1,5%) y Hie (0,5%). Del total de los aislamientos, 12,0% eran resistentes a ampicilina; 16,5% a SXT; 1,0% a cloranfenicol y 0,5% a ceftriaxona. Todos los aislamientos fueron sensibles a cefuroxima y a rifampicina. Conclusiones: La vigilancia por el laboratorio es una vigilancia pasiva voluntaria pero, no obstante el número reducido de aislamientos, permite determinar que Hib continúa circulando en esta población y que hay otros serotipos de H. influenzae que causan enfermedad invasiva. Por tanto es necesario mantener y fortalecer la vigilancia de este patógeno.

Objective: To analyze 2002-2013 surveillance data on the serotypes and antimicrobial sensitivity of invasive Haemophilus influenzae ( H. influenzae ) isolates in children younger than 60 months. Materials and methods: We analyzed the demographic data, source and associated diseases ofinvasive HI isolates from cases recorded from 2002-2013. All isolates had been bacteriologically confirmed and had data on their serotype, which was determined by the slide agglutination method and polymerase chain reaction. The antimicrobial sensitivity patterns were determined by minimum inhibitory concentration of ampicillin, trimethoprim-sulfamethoxazole, chloramp-henicol, cefuroxime and ceftriaxone. The analysis was conducted in 3-year periods. Results: According to invasive disease, 50.5% of patients had meningitis, 23.5% had pneumonia,19.5% had sepsis and bacteremia, 2.0% had other diseases and 4.5% lacked data. By origin, 55 isolates each were received from Bogota and Antioquia, 24 were from Risaralda, 15 were from Valle, 11 were from Santander and 40 came from 14 departments. The predominant serotype was Hib (40.5%), followed by HiNT (38.0%), Hia (17.5%), Hid (2.0%), Hif (1.5%) and Hie (0.5%). Ofthe total isolates, 12.0% were resistant to ampicillin; 16.5% to trimethoprim-sulfamethoxazole,1.0% to chloramphenicol and 0.5% to ceftriaxone. All isolates were sensitive to cefuroxime andrifampicin. Conclusions: Laboratory surveillance is a voluntary passive surveillance; however, the low number of isolates helped determine that Hib continues to circulate in this population and that there are other H. influenzae serotypes that cause invasive disease. Therefore, surveillance of this pathogen needs to be maintained and reinforced.

Retrospective study of the epidemiology and clinical manifestations of Cryptococcus gattii infections in Colombia from 1997-2011.

BACKGROUND: Cryptococcosis due to Cryptococcus gattii is endemic in various parts of the world, affecting mostly immunocompetent patients. A national surveillance study of cryptococcosis, including demographical, clinical and microbiological data, has been ongoing since 1997 in Colombia, to provide insights into the epidemiology of this mycosis. METHODOLOGY/PRINCIPAL FINDINGS: From 1,209 surveys analyzed between 1997-2011, 45 cases caused by C. gattii were reported (prevalence 3.7%; annual incidence 0.07 cases/million inhabitants/year). Norte de Santander had the highest incidence (0.81 cases/million/year), representing 33.3% of all cases. The male: female ratio was 3.3∶1. Mean age at diagnosis was 41±16 years. No specific risk factors were identified in 91.1% of patients. HIV infection was reported in 6.7% of patients, autoimmune disease and steroids use in 2.2%. Clinical features included headache (80.5%), nausea/vomiting (56.1%) and neurological derangements (48.8%). Chest radiographs were taken in 21 (46.7%) cases, with abnormal findings in 7 (33.3%). Cranial CT scans were obtained in 15 (33.3%) cases, with abnormalities detected in 10 (66.7%). Treatment was well documented in 30 cases, with most receiving amphotericin B. Direct sample examination was positive in 97.7% cases. Antigen detection was positive for all CSF specimens and for 75% of serum samples. C. gattii was recovered from CSF (93.3%) and respiratory specimens (6.6%). Serotype was determined in 42 isolates; 36 isolates were serotype B (85.7%), while 6 were C (14.3%). The breakdowns of molecular types were VGII (55.6%), VGIII (31.1%) and VGI (13.3%). Among 44 strains, 16 MLST sequence types (ST) were identified, 11 of them newly reported. CONCLUSIONS/SIGNIFICANCE: The results of this passive surveillance study demonstrate that cryptococcosis caused by C. gattii has a low prevalence in Colombia, with the exception of Norte de Santander. The predominance of molecular type VGII is of concern considering its association with high virulence and the potential to evolve into outbreaks.

Cryptococcosis in Colombian children and literature review.

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.

Cryptococcosis in Colombian children and literature review

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.

Evaluation of a rapid lateral flow immunoassay for the detection of cryptococcal antigen for the early diagnosis of cryptococcosis in HIV patients in Colombia.

A previous study carried out in a tertiary care hospital in Colombia demonstrated the usefulness of the Cryptococcus capsular antigen detection by latex (CrAg Latex) in the early diagnosis of cryptococcosis in HIV-infected patients with low CD4 + levels. The aim of this study was to establish the performance of a new rapid lateral flow assay (CrAg LFA) in preserved sera of those HIV-infected patients collected between 2001 and 2006. A total of 421 sera from 297 patients with a confirmed diagnosis of HIV were tested with CrAg LFA and results compared with those obtained with CrAg Latex. All patients provided informed consent for specimen collection. A concordance of 100% was found between positive results obtained by both methods. However, 13 sera that were negative by CrAg Latex, were positive by CrAg LFA (3.1%). In these positive patients, median of CD4 + levels was 67 cells/µl (8-608 cells/µl), while median of viral load was 118,965 copies/ml (50-500,000 copies/ml). Patients who were negative for cryptococcosis had a median of 177 cells/µl in CD4 + levels (4-2516 cells/µl) and a median of 62,318 copies/ml in viral loads (25-50,000 copies/ml). A significant statistical difference was found when comparing CD4 + levels and viral load in patients positive for cryptococcosis and those that were proven to be negative (P < 0.0001). The use of Point-of-Care Tests (POCT) like CrAg LFA play an important role in the diagnosis of infectious diseases, especially in resource limited settings, where it will be a useful means to diagnose cryptococcosis early in HIV patients.

Cryptococcosis in Colombia: Results of the national surveillance program for the years 2006-2010 / Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Introduction: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. Objective: To analyze the data obtained during this period. Materials and methods: Retrospective analysis of the corresponding surveys. Results: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 106 inhabitants while in AIDS patients this rate rose to 3.3 x 103. In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. Conclusions: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia.

Introducción. Desde 1997 se viene realizando un programa nacional de vigilancia sobre la criptococosis en Colombia. Se presentan los resultados correspondientes a los pacientes diagnosticados entre el 2006 y el 2010. Objetivo. Analizar los datos obtenidos durante este periodo. Materiales y métodos. Análisis retrospectivo de las encuestas. Resultados. Durante los cinco años mencionados se recibieron 526 encuestas representativas del 72 % de la división política colombiana. La mayoría de pacientes (76,6 %) eran hombres y 74,9 % estaban entre los 21 y los 50 años. El factor de riesgo prevalente fue la infección por VIH (83,5 %), y la criptococosis definió el sida en 23 % de los casos. La incidencia anual promedio en la población general fue de 2,4 por un millón de habitantes mientras que, en pacientes con sida, aumentó a 3,3 por 1.000. En 474 encuestas se informaron manifestaciones clínicas; las más frecuentes fueron: cefalea (84,5 %), fiebre (63,4 %), náuseas y vómito (57,5 %), alteraciones mentales (46,3 %), signos meníngeos (33 %), tos (26,4 %) y alteraciones visuales (24,5 %). La neurocriptococosis se reportó en 81,8 % de los casos. El diagnóstico se hizo por examen directo, cultivo y antigenemia en 29,3 % de los casos. De 413 aislamientos recuperados, 95,6 % fueron C. neoformans var. grubii, 1 % C. neoformans var. neoformans, y 3,4 % C. gattii. En 71,6 % de los casos para el tratamiento se administró anfotericina B y en 28 % se combinó con fluconazol. Conclusiones. La vigilancia pasiva continúa siendo un marcador centinela para la infección por VIH, y constituye una aproximación sistemática al estudio de infecciones oportunistas en pacientes con sida, debido a que la criptococosis no es de notificación obligatoria en Colombia.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. METHODS: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. RESULTS: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. CONCLUSIONS: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.

Comparación de los hallazgos clínicos y de supervivencia entre pacientes VIH positivos y VIH negativos con criptococosis meníngea en un hospital de tercer nivel / Comparison of Clinical Findings and Survival Among HIV Positive Patients and HIV-Negative with Cryptococcal Meningitis in a Tertiary Care Hospital

Introducción: en Colombia ha sido documentada la incidencia incrementada de la criptococosis, al igual que una alta prevalencia de criptococosis por C. gattii en Cúcuta. Objetivo: hacer un análisis de los pacientes con criptococosis meníngea atendidos en un hospital de tercer nivel de atención en Cúcuta, Colombia, estableciendo diferencias según su estado de portador del VIH. Materiales y métodos: se realizó un estudio retrospectivo de revisión de historias clínicas en donde se evaluaron las características clínicas y los resultados de los pacientes con diagnóstico de criptococosis meníngea durante el periodo de estudio de 15 años (1996-2010). Resultados: se analizaron 90 casos, 63 (70%) VIH positivos y 27 (30%) VIH negativos. La mayoría de los pacientes VIH positivos fueron adultos jóvenes (81% vs 25.9% de los pacientes VIH negativos, p=<0.001). Hubo una alta prevalencia de niños entre los pacientes VIH negativos (29.6 vs 0%, p= <0.001). La relación hombre: mujer fue mayor en los pacientes VIH positivos (3.8 vs 2.4; p= 0.001). No se encontró factor de riesgo en 88.9% de los pacientes VIH negativos. Entre los pacientes VIH positivos la mayoría (76.2%) no recibía terapia antirretroviral, muy pocos (7.9%) tomaban profilaxis con fuconazol y 68.8% tenía <100 células CD4+. La hipertensión intracraneana sin hidrocefalia (83.3 vs 48.0%, p=0.009), los cambios visuales (48.1 vs 20.6%, p=0.02) y la criptococosis extraneural (22.2 vs 6.4%, p= 0.06) fueron más frecuentes en los pacientes VIH negativos. Los pacientes VIH negativos tuvieron mayor número de leucocitos (124.2/ml vs 43.0/ml, p=0.002) y de proteínas (113.6 vs 89.7 mg/dL, p<0.001) en el LCR. C. neoformans var. grubii se aisló con mayor frecuencia en los pacientes VIH positivos (100 vs 40%, p<0.001) y C. gattii predominó en los VIH negativos (60% vs 0%, p<0.001). La TAC de cráneo fue más frecuentemente anormal en los pacientes VIH positivos (73.3 vs 22.7%, p<0.001). La mayoría de los pacientes en ambos grupos recibieron anfotericina B como terapia primaria (96.8% de los VIH positivos vs 85.2% de los VIH negativos). La letalidad hospitalaria fue mayor en los pacientes VIH positivos (49.2 vs 16.0%, p=0.004). Fueron factores de mal pronóstico: la infección por el VIH, la alteración del estado de conciencia, la falta de terapia antirretroviral en los pacientes VIH positivos, las convulsiones y la baja celularidad en el LCR. Las secuelas neurológicas fueron frecuentes en ambos grupos de pacientes (40.6% vs 32.0%) sin existir diferencia significativa. La probabilidad de supervivencia fue significativamente mayor en los pacientes VIH negativos (82% vs 46%, p=0.0066). Conclusiones: la criptococosis tiene una alta morbilidad y mortalidad, especialmente en los pacientes VIH positivos. Es muy alta la prevalencia de criptococosis por C. gattii y de niños en la población VIH negativa. (Acta Med Colomb 2012; 37: 49-61).

Introduction: an increased incidence of cryptococcosis has been documented in Colombia, as well as a high prevalence of Cryptococcus gattii in Cucuta. Objective: to analyze patients with cryptococcal meningitis treated at a tertiary care hospital in Cucuta, Colombia, according to the HIV carrier status. Materials and methods: we performed a retrospective review of medical records in which we evaluated the clinical characteristics and outcomes of patients diagnosed with cryptococcal meningitis during the study period of 15 years (1996-2010). Results: we analyzed 90 cases, 63 (70%) HIV positive and 27 (30%) HIV negative. Most HIV-positive patients were young adults (81.0% versus 25.9% of HIV negative patients, p = <0.001). There was a high prevalence of children among HIV-negative patients (29.6 versus 0%, p = <0.001). The male: female ratio was higher in HIV positive patients (3.8 versus 2.4, p = 0.001). No risk factor was found in 88.9% of HIV negative patients. Among the HIV-positive patients, mos of them (76.2%) were not receiving antiretroviral therapy, very few (7.9%) were taking prophylaxis with fuconazole and 68.8% had <100 CD4 + cells. Intracranial hypertension without hydrocephalus (83.3 versus 48.0%, p = 0.009), visual changes (48.1 versus 20.6%, p = 0.02) and extraneural cryptococcosis (22.2 versus 6, 4%, p = 0.06) were more frequent in HIV-negative patients. HIV-negative patients had higher numbers of leukocytes (124.2 /ml versus 43.0 /ml, p = 0.002) and protein (113.6 versus 89.7 mg/dL, p <0.001) in the CSF. C. neoformans var. grubii was isolated more frequently in HIV-positive patients (100 versus 40%, p <0.001) and C. gattii was predominant in HIV-negative (60% versus 0%, p <0.001). CT skull was more frequently abnormal in HIV-positive patients (73.3 versus 22.7%, p <0.001). Most patients in both groups received amphotericin B as primary therapy (96.8% of HIV positive versus 85.2% of HIV negative). The hospital mortality was higher in HIV positive patients (49.2 versus 16.0%, p = 0.004). HIV infection, altered state of consciousness, lack of antiretroviral therapy in HIV-positive patients, seizures and low CSF cellularity were factors of poor prognosis. Neurological sequelae were common in both groups of patients (40.6% vs 32.0%) without significant difference. The probability of survival was significantly higher in HIV-negative patients (82% vs 46%, p = 0.0066). (Acta Med Colomb 2012; 37: 49-61) Conclusions: cryptococcosis has a high morbidity and mortality, especially in HIV positive patients. The prevalence of Cryptococcus gattii in the HIV negative population and in children is very high.

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries.

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used.

Cryptococcosis in Colombia: results of the national surveillance program for the years 2006-2010.

INTRODUCTION: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. OBJECTIVE: To analyze the data obtained during this period. MATERIALS AND METHODS: Retrospective analysis of the corresponding surveys. RESULTS: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 106 inhabitants while in AIDS patients this rate rose to 3.3 x 103. In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. CONCLUSIONS: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia.

[Increase in erythromycin-resistant Streptococcus pneumoniae in Colombia, 1994-2008]. / Incremento de la resistencia a eritromicina de Streptococcus pneumoniae, Colombia, 1994-2008.

INTRODUCTION: Streptococcus pneumoniae is a commonly implicated agent in invasive disease. For infections of S. pneumoniae resistant to b-lactam, macrolides are an alternative treatment. However, resistance to macrolides has increased worldwide as well. OBJECTIVE: The frequency of resistance to erythromycin was determined for S. pneumoniae over a 15-year surveillance period, and the resistant isolates were characterized phenotypically and genotypically. MATERIALS AND METHODS: Demographic data of the patients, antimicrobial susceptibility and serotypes were analyzed for 3,241 S. pneumoniae isolates recovered between 1994 and 2008. The phenotypes were determined by the double-disc technique and genotypes by PCR (polymerase chain reaction) and PFGE (pulsed field gel electrophoresis). Isolates were recovered from invasive diseases and were provided by national public health laboratories. RESULTS: Of the 3,241 isolates, 136 were resistant to erythromycin. In the 12-year period between 1994-1996 and 2006-2008, resistance in each 2-year sampling had increased from 2.4% to 6.9% in children under 6 years and from 3.3% to 5.7% in adults. The most common serotypes were 6B (36.8%), 14 (16.9%) and 6A (17.6%). Constitutive phenotype cMLSB was determined in 87 isolates; 82 of these expressed the ermB gene. Phenotype M was determined in 46 isolates; 45 had the mefA gene. An additional three isolates expressed the inducible phenotype (iMLSB), and one expressed the ermB gene. By PFGE, 50 of the isolates were found to be related to international clones--58% were Spain6B-ST90, 26% Spain9V-ST156, 8% Colombia23F-ST338 and 8% Spain23F-ST81. CONCLUSION: The increase in erythromycin resistance was primarily related to the mechanism of ribosomal methylation. More than half the cases were congeneric with the clone Spain6B-ST90 that has been circulating in Colombia since 1994.