Serotypes and antimicrobial resistance of Streptococcus pneumoniae in children under 5 years of age pre- and post-pneumococcal conjugate vaccine introduction in Paraguay.

Introduction. Streptococcus pneumoniae remains a major cause of mortality and morbidity worldwide in children <5 years of age, even with advances in vaccination programmes.Hypothesis/Gap Statement. Reviewing and reporting trends in the distribution of pneumococcal serotypes and antimicrobial resistance in Paraguay will be useful for decision-making in public health.Aim. This study analysed the serotype distribution and antimicrobial resistance of S. pneumoniae and the characteristics of pneumococcal disease in children <5 years old before and after the introduction of pneumococcal conjugate vaccines (PCVs).Methodology. A total of 885 isolates and 278 S. pneumoniae PCR-positive clinical specimens were referred to the Central Laboratory of Public Health (LCSP) within the meningitis and pneumonia laboratory based-surveillance network in the period 2006-2020. Conventional and molecular microbiological techniques were used for confirmation and characterization.Results. We identified 563 cases of pneumococcal disease in the pre-vaccination period, 325 cases in the post-PCV10 period and 275 cases in the post-PCV13 period. The serotypes covered by PCV10 decreased from 78.6-6.5 %. However, additional serotypes covered by PCV13 increased from 6.6-57.5% and non-PCV13 serotypes increased from 14.8-36.0 % (P<0.001) in the post-PCV13 period. In cases of meningitis, the rate of resistance to penicillin decreased after the introduction of conjugate vaccines. No resistance to ceftriaxone was found in any period. In cases without meningitis, the rate of resistance to penicillin and ceftriaxone decreased slightly. However, the rate of resistance to erythromycin and tetracycline increased and that to trimethoprim-sulfamethoxazole (SXT) decreased in the post-PCV13 period compared to the pre-PCV period. The multidrug resistance rate was 8.5 %.Conclusion. A change in the circulating serotypes and antimicrobial resistance to certain antibiotics was observed. Non-vaccine serotype circulation and multidrug resistance may compromise the success of the conjugate vaccines.

Nasopharyngeal colonization by Streptococcus pneumoniae in children and adults before the introduction of the 10-valent conjugate vaccine, Paraguay.

Streptococcus pneumoniae is a cause of invasive diseases such as pneumonia, meningitis, and other serious infections among children and adults in Paraguay. This study was conducted to establish S. pneumoniae baseline prevalence, serotype distribution, and antibiotic resistance patterns in healthy children aged 2 to 59 months and adults ≥60 years of age prior to the introduction of PCV10 in the national childhood immunization program in Paraguay. Between April and July 2012, a total of 1444 nasopharyngeal swabs were collected, 718 from children aged 2 to 59 months and 726 from adults ≥60 years of age. The pneumococcal isolation, serotyping, and antibiotic susceptibility testing were performed using standard tests. Pneumococcal colonization prevalence was 34.1% (245/718) in children and 3.3% (24/726) in adults. The most frequent pneumococcal vaccine-types (VT) detected in the children were 6B (42/245), 19F (32/245), 14 (17/245), and 23F (20/245). Carriage prevalence with PCV10 serotypes was 50.6% (124/245) and PCV13 was 59.5% (146/245). Among colonized adults, prevalence of PCV10 and PCV13 serotypes were 29.1% (7/24) and 41.6% (10/24), respectively. Colonized children were more likely to share a bedroom, have a history of respiratory infection or pneumococcal infection compared to non-colonized children. no associations were found in adults. However, no significant associations were found in children and neither in adults. Vaccine-type pneumococcal colonization was highly prevalent in children and rare in adults in Paraguay prior to vaccine introduction, supporting the introduction of PCV10 in the country in 2012. These data will be useful to evaluate the impact of PCV introduction in the country.

Serogrupos y resistencia antimicrobiana de Neisseria meningitidis causantes de enfermedad invasiva en Paraguay

RESUMEN La enfermedad meningocócica representa un problema de salud pública y una de las principales causas de morbilidad y mortalidad en todo el mundo. Los serogrupos que causan la mayor carga de enfermedad a nivel global son A, B, C, W e Y. El objetivo del estudio fue describir los serogrupos y la resistencia antimicrobiana de Neisseria meningitidis aisladas de enfermedad invasiva en Paraguay durante el periodo 2010-2020. Se estudiaron todas las muestras de líquido cefalorraquídeo y sangre con aislamientos o detección de ADN por PCR de N. meningitidis de pacientes de diversas edades, que fueron remitidas al Laboratorio Central de Salud Pública durante el periodo 2010-2020, dentro del marco de la vigilancia epidemiológica de meningitis (n=163) en Paraguay. La mayor frecuencia de hallazgos de N. meningitidis se observó en el grupo de edad de < 1 año. El 25,7% de los casos correspondió al serogrupo B, el 52,1% al serogrupo C, 18,4% al serogrupo W y 3,7% al serogrupo Y. En el 2018, se evidenció la mayor cantidad de casos por serogrupo C (n=27). La menor frecuencia de sensibilidad disminuida a penicilina G fue en el 2010 (12,5%) y la mayor en el 2014 (100,0%). Se registró un aumento de casos por serogrupo C a partir del 2017, posicionándose como serogrupo prevalente hasta el 2020, y además, un aumento de la sensibilidad disminuida a la penicilina. La vigilancia es de importancia en el control de la enfermedad meningocócica para detección de brotes, estimación de la carga de enfermedad, análisis de resistencia antimicrobiana, distribución de serogrupos y evaluaciones de estrategias de control.

ABSTRACT Meningococcal disease represents a public health problem and one of the main causes of morbidity and mortality worldwide. The serogroups that cause the highest burden of disease globally are A, B, C, W, and Y. The aim of the study was to describe serogroups and antimicrobial resistance of Neisseria meningitidis isolated from invasive disease in Paraguay during the 2010-2020 period. Samples of cerebrospinal fluid and blood with isolates or detection of DNA by PCR of N. meningitidis from patients of different ages referred to the Central Public Health Laboratory during the period 2010-2020 within the framework of the epidemiological surveillance of meningitis (n = 163) in Paraguay were studied. The highest frequency of N. meningitidis findings was observed in the <1 year age group, 25.7% of the cases corresponded to serogroup B, 52.1% to serogroup C, 18.4% to serogroup W and 3.7% to serogroup Y. In 2018, the highest number of cases by serogroup C (n = 27) was found. The lowest frequency of decreased sensitivity to penicillin G was in 2010 (12.5%) and the highest in 2014 (100.0%). There was an increase in cases due to serogroup C in 2017, positioning itself as the prevalent serogroup until 2020, in addition, there was an increase in decreased sensitivity to penicillin. Surveillance is important in the control of meningococcal disease for outbreak detection, estimation of the burden of disease, analysis of antimicrobial resistance, serogroup distribution, and evaluations of control strategies.

Estudio epidemiológico de Haemophilus influenzae causante de enfermedad invasiva y no invasiva en Paraguay (1999-2017) / Epidemiologic study of Haemophilus influenzae causing invasive and non-invasive disease in Paraguay (1999-2017)

Introducción: Haemophilus influenzae (Hi) causa infecciones leves e invasivas graves, especialmente en niños menores de 5 años. El serotipo b (Hib) era muy frecuente antes de la introducción de la vacuna, que en Paraguay se introdujo en 2004. Métodos: Se estudiaron por métodos microbiológicos convencionales y técnicas moleculares 523 aislados de H. influenzae obtenidos desde 1999 a 2017 y remitidos al Laboratorio Nacional de Referencia de Paraguay. Resultados: El serotipo más frecuente fue el no-tipable (HiNT), en un 51,8% (271/523), seguido de Hib (43%; 225/523), Hia e Hif (1,5%; 8/523, respectivamente), Hic (1%; 5/523), Hie (0,8%; 4/523) y Hid (0,4%; 2/523). El 48,4% de las infecciones invasivas estaban causadas por HiNT y el 46,1% por Hib. El 88,6% de las cepas procedían de casos de meningitis, el 70,8% de sepsis y el 50,9% de neumonías en niños menores de 5 años. El 84% (181/217) de las cepas correspondían a enfermedades invasivas causadas por Hib en menores de 5 años, registrándose la mayor proporción entre 2001-2003. Los biotipos más prevalentes fueron el biotipo I (29%), biotipo II (12%), biotipo III (24%) y biotipo IV (13%). El 13% (68/523) de los aislados fueron resistentes a la ampicilina. Conclusión: Tras de la introducción de la vacuna frente a Hib en Paraguay, los casos de enfermedad invasiva por Hib disminuyeron en niños menores de 5 años y hubo un aumento de HiNT en los mayores de 5 años. Es necesaria una vigilancia continua para monitorizar la eficacia de la vacuna y desarrollar intervenciones preventivas.(AU)

Introduction: Haemophilus influenzae is a cause of mild and severe invasive infections, especially among children under 5 years old. Serotype b (Hib) was very frequent before the introduction of the vaccine, which was introduced in Paraguay in 2004. Methods: A total of 523 isolates of H. influenzae obtained from 1999 to 2017 and referred to the National Reference Laboratory in Paraguay were studied by conventional microbiological methods and molecular techniques. Results: The most frequent serotype was non-typeable (HiNT) (51.8%; 271/523), followed by Hib (43%; 225/523), Hia and Hif (1.5%; 8/523, respectively), Hic (1%; 5/523), Hie (0.8%; 4/523), and Hid (0.4%; 2/523). A total of 48.4% invasive infections were caused by HiNT, and 46.1% by Hib; 88.6% of isolates corresponded to meningitis, 70.8% to sepsis and 50.9% to pneumonia in children under 5 years. A total of 84% (181/217) of isolates corresponded to invasive infections caused by Hib in children under 5 years, with the highest proportion observed between 2001 and 2003. The most prevalent biotypes were biotype I (29%), biotype II (12%), biotype III (24%), and biotype IV (13%). Among the total of isolates, 13% (68/523) of isolates were resistant to ampicillin. Conclusion: After the introduction of the Hib vaccine in Paraguay, the number of invasive Hib cases decreased in children under 5 years old, although we observed an increase of HiNT in children over 5 years. Continuous surveillance is necessary in order to monitor the effectiveness of the vaccine and for the development of preventive interventions.(AU)

Epidemiologic study of Haemophilus influenzae causing invasive and non-invasive disease in Paraguay (1999-2017). / Estudio epidemiológico de Haemophilus influenzae causante de enfermedad invasiva y no invasiva en Paraguay (1999-2017).

INTRODUCTION: Haemophilus influenzae is a cause of mild and severe invasive infections, especially among children under 5 years old. Serotype b (Hib) was very frequent before the introduction of the vaccine, which was introduced in Paraguay in 2004. METHODS: A total of 523 isolates of H. influenzae obtained from 1999 to 2017 and referred to the National Reference Laboratory in Paraguay were studied by conventional microbiological methods and molecular techniques. RESULTS: The most frequent serotype was non-typeable (HiNT) (51.8%; 271/523), followed by Hib (43%; 225/523), Hia and Hif (1.5%; 8/523, respectively), Hic (1%; 5/523), Hie (0.8%; 4/523), and Hid (0.4%; 2/523). A total of 48.4% invasive infections were caused by HiNT, and 46.1% by Hib; 88.6% of isolates corresponded to meningitis, 70.8% to sepsis and 50.9% to pneumonia in children under 5 years. A total of 84% (181/217) of isolates corresponded to invasive infections caused by Hib in children under 5 years, with the highest proportion observed between 2001 and 2003. The most prevalent biotypes were biotype I (29%), biotype II (12%), biotype III (24%), and biotype IV (13%). Among the total of isolates, 13% (68/523) of isolates were resistant to ampicillin. CONCLUSION: After the introduction of the Hib vaccine in Paraguay, the number of invasive Hib cases decreased in children under 5 years old, although we observed an increase of HiNT in children over 5 years. Continuous surveillance is necessary in order to monitor the effectiveness of the vaccine and for the development of preventive interventions.

Frecuencia de Streptococcus pneumoniae aislados de enfermedad invasiva en Paraguay, serotipos y perfil de sensibilidad (2010-2018) / Frequency of Streptococcus pneumoniae isolated from invasive disease in Paraguay, serotypes and sensitivity profile (2010-2018)

Streptococcus pneumoniae sigue siendo una de las causas más importantes de morbilidad y mortalidad en niños y adultos alrededor del mundo. El objetivo del estudio fue describir la frecuencia de aislamiento de S. pneumoniae en enfermedad invasiva, distribución de serotipos y sensibilidad antimicrobiana en Paraguay (2010-2018). Se estudiaron 793 cepas de S. pneumoniae aisladas de pacientes de todas las edades con enfermedad invasiva en Paraguay, provenientes de los diferentes centros centinelas y colaboradores en el marco de la vigilancia de meningitis y neumonías, durante el periodo 2010-2018. La frecuencia general según diagnóstico resultó 74.9% de neumonías (n=594), 18.4% de meningitis (n=146) y 6.7% de sepsis (n=53). El serotipo 14 fue más frecuente con 174 aislamientos (22.0%), seguido del serotipo 19A con 84 aislamientos (10.6%), el serotipo 3 con 66 aislamientos (8.3%) y el 6A con 37 aislamientos (4.7%). En meningitis se registró una frecuencia general de resistencia a penicilina del 32,2% y de ceftriaxona del 1,4%. En los casos de no meningitis la resistencia a penicilina fue del 0,8% y ceftriaxona del 0,3%. Los resultados de serotipos y sensibilidad antimicrobiana proporcionarán información necesaria para la implementación de estrategias de prevención y tratamiento de la enfermedad neumocócica en nuestro país, por lo que es necesaria una vigilancia continua para evaluar la carga de enfermedad, los serotipos circulantes y el aumento de la resistencia a los antibióticos

Streptococcus pneumoniae remains one of the most important causes of morbidity and mortality in children and adults worldwide. The objective of the study was to describe the frequency of isolation of S. pneumoniae in invasive disease, serotype distribution and antimicrobial susceptibility in Paraguay (2010-2018). We studied 793 strains of S. pneumoniae isolated from patients of all ages with invasive disease in Paraguay, from different sentinel centers and collaborators in the framework of meningitis and pneumonia surveillance during the period 2010-2018. The general frequency according to diagnosis was 74.9% of pneumonia (n = 594), 18.4% of meningitis (n = 146) and 6.7% of sepsis (n = 53). Serotype 14 was more frequent with 174 isolates (22.0%), followed by serotype 19A with 84 isolates (10.6%), serotype 3 with 66 isolates (8.3%) and 6A with 37 isolates (4.70%). In meningitis, there was a general frequency of penicillin resistance of 32.2% and ceftriaxone of 1.4%. In cases of non-meningitis, penicillin resistance was 0.8% and ceftriaxone 0.3%. The results of serotypes and antimicrobial sensitivity will provide necessary information for the implementation of prevention strategies and treatment of pneumococcal disease in our country, therefore it is necessary to continue monitoring in order to assess the burden of the disease, circulating serotypes and increased antibiotic resistance

Carriage of Neisseria meningitidis and other Neisseria species among children and young adults in Paraguay.

Introduction. Colonization by Neisseria meningitidis is the pre-requisite for the development of disease. We present the findings of a cross-sectional investigation onto the oropharyngeal carriage of N. meningitidis and Neisseria species in the population aged 3 to 21 in Paraguay.Aim. Carriage prevalence by age groups, risk factors associated with carriage, and phenotypic and genotypic characteristics of strains are described.Methodology. We collected 2011 oropharyngeal swabs from consenting participants aged 3-21 years. Infants were recruited at immunization clinics, and older children and young adults were identified at schools and universities. A single oropharyngeal swab was collected and processed for the identification and isolation of Neisseria. Additionally, participants, or their legal guardian if these were minors, were requested to fill a standardized questionnaire.Results. N. meningitidis was isolated in 42/2011 (2.1 %) participants, while other Neisseria spp. were identified in 306/2011 (15.2 %) subjects: N. cinerea and N. lactamica were identified in 39/2011 (1.9 %) and 43/2011 (2.2 %), respectively. Meningococcal strains belonged to ten different clonal complexes, of which six are associated with invasive disease (ST-32/ET5 complex, ST-11/ET37 complex, ST-103 complex, ST-167 complex, ST-35 complex and ST-41/44 complex/lineage 3).Conclusion. Prevalence of N. meningitidis carriage was low compared to that reported from other settings, however, the overall carriage of Neisseria spp. (including N. meningitidis) was comparable to meningococcal carriage prevalence reported in the literature. This study is the first of its kind conducted in Paraguay, and one of the few known in the Southern Cone of Latin America.

[Genotypes of Neisseria meningitidis isolates in patients with meningococcal meningitis in Paraguay, 1996-2015Genótipos de Neisseria meningitidis isolados de pacientes com doença meningocócica no Paraguai, 1996-2015]. / Genotipos de Neisseria meningitidis aislados de pacientes con enfermedad meningocócica en Paraguay, 1996-2015.

OBJECTIVE: Describe the phenotypical and genotypical characteristics of Neisseria meningitidis isolates from cases of meningococcal disease in Paraguay between 1996 and 2015. METHODS: Conventional microbiological methods and molecular techniques were used to study 114 isolates of N. meningitidis and 12 clinical samples without isolation (confirmed by polymerase chain reaction), provided by various sentinel centers and collaborating centers in Paraguay. RESULTS: The most affected age group was children under 1 year (19.0%), followed by 1-5-year-olds (17.5%). The highest percentage of strains was isolated in meningitis cases (81.7%) and serogroup B was found in 60.3% of cases. The most frequent phenotypes were B:4:p1.14 (16.0%), B:15:p1.5, C:nt:nst, and W:nt:p1.2 (10.5%), respectively. The prevalent clonal complexes were: ST-11/ET37 complex, 29.6% (8/27), predominantly serogroup W (6/8); ST-35 complex, 18.5% (5/27), in serogroup B (4/4); and ST-32/ET5 complex, 14.8% (4/16), in serogroup B (5/5). CONCLUSIONS: Meningococcal meningitis is relatively uncommon in Paraguay. Distribution analysis showed that serogroup B is the most common and that the number of cases of meningococcal disease caused by serogroups C and W increased in the last two years. The identified clonal complexes were correlated with those found in the Southern Cone region. Due to the high virulence of N. meningitidis, its surveillance should be a strategic priority of national and regional public health systems to prevent epidemic outbreaks and support public health decision-making.

OBJETIVO: Descrever as características fenotípicas e genotípicas de cepas de Neisseria meningitidis isoladas de casos de doença meningocócica no Paraguai entre 1996 e 2015. MÉTODOS: Foram estudados por métodos microbiológicos convencionais e técnicas moleculares 114 isolados de N. meningitidis e 12 amostras clínicas sem isolamento confirmadas por reação em cadeia da polimerase (PCR) enviados por diferentes centros-sentinela e centros colaboradores do Paraguai. RESULTADOS: A faixa etária mais afetada foi a de crianças menores de 1 ano (19,0%) e crianças de 1 a 5 anos (17,5%). Uma maior porcentagem de cepas foi isolada de casos de meningite (81,7%) e o sorogrupo B foi identificado em 60,3% dos casos. Os fenótipos mais comuns foram B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST e W:NT:P1.2 (10,5%), respectivamente. Os complexos clonais mais prevalentes foram o complexo ST-11/ET37 (29,6%, 8/27) com predomínio no sorogrupo W (6/8), complexo ST-35 (18,5%, 5/27) no sorogrupo B (4/4) e complexo ST-32/ET5 (14,8%, 4/16) no sorogrupo B (5/5). CONCLUSÕES: A doença meningocócica é relativamente pouco comum no Paraguai. A análise da distribuição dos sorogrupos demonstrou que o sorogrupo B é o mais prevalente e, nos últimos dois anos, ouve um aumento nos casos de doença meningocócica pelos sorogrupos C e W. Os complexos clonais encontrados se correlacionam com os achados na região do Cone Sul. Devido à alta virulência da N. meningitidis, a vigilância deste agente deve ser uma prioridade estratégica dos sistemas de saúde pública nacionais e regionais para prevenir surtos epidêmicos e subsidiar a tomada de decisão em saúde pública.

Genotipos de Neisseria meningitidis aislados de pacientes con enfermedad meningocócica en Paraguay, 1996–2015

[RESUMEN]. Objetivo. Describir las características fenotípicas y genotípicas de cepas de Neisseria meningitidis aisladas de enfermedad meningocócica en Paraguay entre 1996 y 2015. Métodos. Se estudiaron por métodos microbiológicos convencionales y técnicas moleculares 114 aislamientos de N. meningitidis y 12 muestras clínicas sin aislamiento confirmadas por reacción en cadena de la polimerasa (PCR) que fueron remitidas por los diferentes centros centinelas y centros colaboradores de Paraguay. Resultados. El grupo de edad más afectado fue el de menores de 1 año (19,0%), seguido por el de 1 a 5 años (17,5%). Un mayor porcentaje de las cepas se aisló de casos de meningitis (81,7%) y el serogrupo B se encontró en 60,3% de los casos. Los fenotipos más frecuentes fueron B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST y W:NT:P1.2 (10,5%), respectivamente. Los complejos clonales prevalentes fueron ST-11/ET37 complex 29,6% (8/27) con predominio del serogrupo W (6/8), ST-35 complex 18,5% (5/27) en el serogrupo B (4/4), y ST-32/ET5 complex 14,8% (4/16) en el serogrupo B (5/5). Conclusiones. En Paraguay la enfermedad meningocócica es relativamente infrecuente. Los análisis de distribución de serogrupo muestran que el más frecuente es el B y en los últimos dos años aumentaron los casos de enfermedad meningocócica por C y W. Los complejos clonales encontrados se correlacionan con los hallados en la región del Cono Sur. Debido al alto nivel de virulencia de N. meningitidis, su vigilancia debe constituir una prioridad estratégica de los sistemas de salud pública nacionales y regionales para prevenir brotes epidémicos y apoyar la toma de decisiones en salud pública.

[ABSTRACT]. Objective. Describe the phenotypical and genotypical characteristics of Neisseria meningitidis isolates from cases of meningococcal disease in Paraguay between 1996 and 2015. Methods. Conventional microbiological methods and molecular techniques were used to study 114 isolates of N. meningitidis and 12 clinical samples without isolation (confirmed by polymerase chain reaction), provided by various sentinel centers and collaborating centers in Paraguay. Results. The most affected age group was children under 1 year (19.0%), followed by 1-5-year-olds (17.5%). The highest percentage of strains was isolated in meningitis cases (81.7%) and serogroup B was found in 60.3% of cases. The most frequent phenotypes were B:4:p1.14 (16.0%), B:15:p1.5, C:nt:nst, and W:nt:p1.2 (10.5%), respectively. The prevalent clonal complexes were: ST-11/ET37 complex, 29.6% (8/27), predominantly serogroup W (6/8); ST-35 complex, 18.5% (5/27), in serogroup B (4/4); and ST-32/ET5 complex, 14.8% (4/16), in serogroup B (5/5). Conclusions. Meningococcal meningitis is relatively uncommon in Paraguay. Distribution analysis showed that serogroup B is the most common and that the number of cases of meningococcal disease caused by serogroups C and W increased in the last two years. The identified clonal complexes were correlated with those found in the Southern Cone region. Due to the high virulence of N. meningitidis, its surveillance should be a strategic priority of national and regional public health systems to prevent epidemic outbreaks and support public health decision-making.

[RESUMO]. Objetivo. Descrever as características fenotípicas e genotípicas de cepas de Neisseria meningitidis isoladas de casos de doença meningocócica no Paraguai entre 1996 e 2015. Métodos. Foram estudados por métodos microbiológicos convencionais e técnicas moleculares 114 isolados de N. meningitidis e 12 amostras clínicas sem isolamento confirmadas por reação em cadeia da polimerase (PCR) enviados por diferentes centrossentinela e centros colaboradores do Paraguai. Resultados. A faixa etária mais afetada foi a de crianças menores de 1 ano (19,0%) e crianças de 1 a 5 anos (17,5%). Uma maior porcentagem de cepas foi isolada de casos de meningite (81,7%) e o sorogrupo B foi identificado em 60,3% dos casos. Os fenótipos mais comuns foram B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST e W:NT:P1.2 (10,5%), respectivamente. Os complexos clonais mais prevalentes foram o complexo ST-11/ET37 (29,6%, 8/27) com predomínio no sorogrupo W (6/8), complexo ST-35 (18,5%, 5/27) no sorogrupo B (4/4) e complexo ST-32/ET5 (14,8%, 4/16) no sorogrupo B (5/5). Conclusões. A doença meningocócica é relativamente pouco comum no Paraguai. A análise da distribuição dos sorogrupos demonstrou que o sorogrupo B é o mais prevalente e, nos últimos dois anos, ouve um aumento nos casos de doença meningocócica pelos sorogrupos C e W. Os complexos clonais encontrados se correlacionam com os achados na região do Cone Sul. Devido à alta virulência da N. meningitidis, a vigilância deste agente deve ser uma prioridade estratégica dos sistemas de saúde pública nacionais e regionais para prevenir surtos epidêmicos e subsidiar a tomada de decisão em saúde pública.

Genotipos de Neisseria meningitidis aislados de pacientes con enfermedad meningocócica en Paraguay, 1996-2015 / Genotypes of Neisseria meningitidis isolates in patients with meningococcal meningitis in Paraguay, 1996-2015 / Genótipos de Neisseria meningitidis isolados de pacientes com doença meningocócica no Paraguai, 1996-2015

RESUMEN Objetivo Describir las características fenotípicas y genotípicas de cepas de Neisseria meningitidis aisladas de enfermedad meningocócica en Paraguay entre 1996 y 2015. Métodos Se estudiaron por métodos microbiológicos convencionales y técnicas moleculares 114 aislamientos de N. meningitidis y 12 muestras clínicas sin aislamiento confirmadas por reacción en cadena de la polimerasa (PCR) que fueron remitidas por los diferentes centros centinelas y centros colaboradores de Paraguay. Resultados El grupo de edad más afectado fue el de menores de 1 año (19,0%), seguido por el de 1 a 5 años (17,5%). Un mayor porcentaje de las cepas se aisló de casos de meningitis (81,7%) y el serogrupo B se encontró en 60,3% de los casos. Los fenotipos más frecuentes fueron B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST y W:NT:P1.2 (10,5%), respectivamente. Los complejos clonales prevalentes fueron ST-11/ET37 complex 29,6% (8/27) con predominio del serogrupo W (6/8), ST-35 complex 18,5% (5/27) en el serogrupo B (4/4), y ST-32/ET5 complex 14,8% (4/16) en el serogrupo B (5/5). Conclusiones En Paraguay la enfermedad meningocócica es relativamente infrecuente. Los análisis de distribución de serogrupo muestran que el más frecuente es el B y en los últimos dos años aumentaron los casos de enfermedad meningocócica por C y W. Los complejos clonales encontrados se correlacionan con los hallados en la región del Cono Sur. Debido al alto nivel de virulencia de N. meningitidis, su vigilancia debe constituir una prioridad estratégica de los sistemas de salud pública nacionales y regionales para prevenir brotes epidémicos y apoyar la toma de decisiones en salud pública.

ABSTRACT Objective Describe the phenotypical and genotypical characteristics of Neisseria meningitidis isolates from cases of meningococcal disease in Paraguay between 1996 and 2015. Methods Conventional microbiological methods and molecular techniques were used to study 114 isolates of N. meningitidis and 12 clinical samples without isolation (confirmed by polymerase chain reaction), provided by various sentinel centers and collaborating centers in Paraguay. Results The most affected age group was children under 1 year (19.0%), followed by 1-5-year-olds (17.5%). The highest percentage of strains was isolated in meningitis cases (81.7%) and serogroup B was found in 60.3% of cases. The most frequent phenotypes were B:4:p1.14 (16.0%), B:15:p1.5, C:nt:nst, and W:nt:p1.2 (10.5%), respectively. The prevalent clonal complexes were: ST-11/ET37 complex, 29.6% (8/27), predominantly serogroup W (6/8); ST-35 complex, 18.5% (5/27), in serogroup B (4/4); and ST-32/ET5 complex, 14.8% (4/16), in serogroup B (5/5). Conclusions Meningococcal meningitis is relatively uncommon in Paraguay. Distribution analysis showed that serogroup B is the most common and that the number of cases of meningococcal disease caused by serogroups C and W increased in the last two years. The identified clonal complexes were correlated with those found in the Southern Cone region. Due to the high virulence of N. meningitidis, its surveillance should be a strategic priority of national and regional public health systems to prevent epidemic outbreaks and support public health decision-making.

RESUMO Objetivo Descrever as características fenotípicas e genotípicas de cepas de Neisseria meningitidis isoladas de casos de doença meningocócica no Paraguai entre 1996 e 2015. Métodos Foram estudados por métodos microbiológicos convencionais e técnicas moleculares 114 isolados de N. meningitidis e 12 amostras clínicas sem isolamento confirmadas por reação em cadeia da polimerase (PCR) enviados por diferentes centros-sentinela e centros colaboradores do Paraguai. Resultados A faixa etária mais afetada foi a de crianças menores de 1 ano (19,0%) e crianças de 1 a 5 anos (17,5%). Uma maior porcentagem de cepas foi isolada de casos de meningite (81,7%) e o sorogrupo B foi identificado em 60,3% dos casos. Os fenótipos mais comuns foram B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST e W:NT:P1.2 (10,5%), respectivamente. Os complexos clonais mais prevalentes foram o complexo ST-11/ET37 (29,6%, 8/27) com predomínio no sorogrupo W (6/8), complexo ST-35 (18,5%, 5/27) no sorogrupo B (4/4) e complexo ST-32/ET5 (14,8%, 4/16) no sorogrupo B (5/5). Conclusões A doença meningocócica é relativamente pouco comum no Paraguai. A análise da distribuição dos sorogrupos demonstrou que o sorogrupo B é o mais prevalente e, nos últimos dois anos, ouve um aumento nos casos de doença meningocócica pelos sorogrupos C e W. Os complexos clonais encontrados se correlacionam com os achados na região do Cone Sul. Devido à alta virulência da N. meningitidis, a vigilância deste agente deve ser uma prioridade estratégica dos sistemas de saúde pública nacionais e regionais para prevenir surtos epidêmicos e subsidiar a tomada de decisão em saúde pública.

Epidemiología, clínica y factores pronósticos de Enfermedad Meningocóccica Invasora en un centro de referencia de Paraguay. 2005 a 2018

Resumen Introducción: La enfermedad meningocóccica ha sido y sigue siendo una causa importante de morbilidad y mortalidad. Objetivos: Analizar las características clínicas y epidemiológicas de pacientes con infección meningocóccica invasora hospitalizados en un centro hospitalario de referencia. Materiales y métodos: Estudio descriptivo, observacional y retrospectivo de revisión de historias clínicas de pacientes internados entre los años 2005 y 2018 en el Instituto de Medicina Tropical con aislamiento o detección de N. meningitidis en sangre o LCR. Resultados: Fueron captados 44 pacientes con enfermedad meningocóccica invasora durante el periodo estudiado (3±2 casos/año). Los casos predominaron en el grupo etario 15000 /mm3 (p=0,03), la plaquetopenia15000 /mm3, la leucopenia <5000/ mm3, y la plaquetopenia se asociaron a mayor mortalidad.

Abstract Introduction: Meningococcal disease has been and continues to be an important cause of morbidity and mortality around the world. Objectives: To analyze the clinical and epidemiological characteristics of patients with invasive meningococcal infection hospitalized in a reference hospital center. Materials and methods: A descriptive, observational and retrospective study based in the review of clinical records of patients admitted between 2005 and 2018 in the Institute of Tropical Medicine in whom Neisseria meningitidis was isolated o detected by PCR in blood or CSF. Results: Forty-four patients with invasive meningococcal disease were recruited during the period studied (3 ± 2 cases/year). The cases predominated in the age group 15000/mm3 (p=0.03), thrombocytopenia15,000/mm3, leukopenia <5000 / mm3, and thrombocytopenia were associated with increased mortality.

Characterization of type I interferon responses in dengue and severe dengue in children in Paraguay.

BACKGROUND: Infection with dengue virus (DENV) produces a wide spectrum of clinical illness ranging from asymptomatic infection to mild febrile illness, and to severe forms of the disease. Type I interferons (IFNs) represent an initial and essential host defense response against viruses. DENV has been reported to trigger a robust type I IFN response; however, IFN-α/ß profile in the progression of disease is not well characterized. OBJECTIVES AND STUDY DESIGN: In this context, we conducted a retrospective study assessing the circulating serum levels of type I IFNs and related cytokines at different phases of illness in children during the 2011 outbreak of DENV in Paraguay. Demographic, clinical, laboratory and virological data were analyzed. RESULTS: During defervescence, significantly higher levels of IFN-ß, IL-6 and MIP-1ß, were detected in severe vs. non-severe dengue patients. Additionally, a significant positive correlation between INF-α and viremia was detected in children with severe dengue. A significant positive correlation was also observed between IFN-ß serum levels and hematocrit during the febrile phase, whereas IFN-α levels negatively correlated with white blood cells during defervescence in severe dengue patients. Furthermore, previous serologic status of patients to DENV did not influence type I IFN production. CONCLUSIONS: The distinct type I IFN profile in children with dengue and severe dengue, as well as its association with viral load, cytokine production and laboratory manifestations indicate differences in innate and adaptive immune responses that should be investigated further in order to unveil the association of immunological and physiological pathways that underlie in DENV infection.

Enfermedad Meningocóccica Invasora: 15 años de Experiencia en un Centro de Referencia

Introducción: La enfermedad meningocóccica ha sido y sigue siendo una causa importante de morbilidad y mortalidad a nivel mundial. Objetivo General: Analizar las características clínicas y epidemiológicas de pacientes con infección meningocóccica invasora hospitalizados en un centro hospitalario de referencia. Materiales y método: Estudio descriptivo, observacional y retrospectivo de revisión de historias clínicas de los pacientes de edad ≤ 15 años ingresados en el Servicio de Pediatría del Instituto de Medicina Tropical con aislamiento o detección de N. meningitidis en sangre, LCR u otro fluido estéril, durante el periodo de enero de 1998 a diciembre de 2013. Resultados: Fueron captados 22 pacientes con enfermedad meningocóccica invasora durante el periodo estudiado (1-2 casos/año), con distribución similar para ambos sexos, predominio de <5 años (73%). 12 pacientes (54%) presentaron meningitis y 10 (45%) meningococcemia. Los síntomas predominantes fueron fiebre (100%) y vómitos (90%). Los signos predominantes fueron signos meníngeos (+) (45%), choque (36%) y púrpura (36%). (32%) requirieron ingreso a Unidad de Cuidados Intensivos. Se halló una letalidad del 13% (3 pacientes), todos con meningococcemia. El B fue el serogrupo predominante, (63%), seguido de los serogrupos C y Y/W135. Durante los últimos 5 años el serogrupo B totalizó las muestras remitidas. La meningococcemia (p=0.09), edad < 5 años (p=0.04), presencia de choque (p ≤ 0.01), síndrome purpúrico (p≤0.01) y Glasgow ≤12 (p=0.02) se asociaron con mayor ingreso a UCI. La plaquetopenia < 100.000 se asoció significativamente a ingreso a UCI (p=0.02). El serogrupo B, el más frecuente en toda la población estudiada, tuvo cierta preponderancia en el grupo de ingreso a UCI (p=0.2). Conclusión: La enfermedad meningocóccica presenta un patrón estable de endemicidad en nuestro país. En nuestro estudio el serogrupo B fue el predominante, y hegemónico en los últimos 5 años. La meningococcemia, edad < 5 años, presencia de choque, síndrome purpúrico y Glasgow ≤12 (p=0.02) se asociaron con mayor gravedad. La vigilancia continua es crucial para guiar las estrategias de prevención y control de la enfermedad meningocóccica

Abstrac Introduction: Meningococcal disease has been and remains an important cause of morbidity and mortality worldwide. Objective: To analyze the clinical and epidemiological characteristics of patients with invasive meningococcal infection hospitalized in a hospital of reference. Materials and Methods: A descriptive, observational and retrospective study of review of medical records of patients of age ≤15 years admitted to the Pediatrics Institute of Tropical Medicine in isolation or detection of N. meningitidis in blood, CSF or other sterile fluid, during the period January 1998 to December 2013. Results: 22 patients were captured with invasive meningococcal disease during the period studied (1-2 cases / year), with similar distribution for both sexes, prevalence of <5 years (73%) of 12 patients (54%) had meningitis and 10. (45%) meningococcemia. The predominant symptoms were fever (100%) and vomiting (90%). The predominant signs were meningeal signs (+) (45%), shock (36%) and purple (36%). (32%) required admission to intensive care unit. A fatality rate of 13% (3 patients), all with meningococcemia was found. The serogroup B was the predominant (63%), followed by serogroups C and Y / W135.Durante the last 5 years serogroup B samples totaled forwarded. Meningococcemia (p = 0.09), age < 5 years (p = 0.04), presence of shock (p ≤ 0.01), purpuric syndrome (p ≤ 0.01) and Glasgow ≤ 12 (p = 0.02) were associated with increased ICU admission. Thrombocytopenia < 100,000 was significantly associated with ICU admission (p = 0.02). Serogroup B, the most common in the entire study population, had some preponderance in the ICU income group (p = 0.2). Conclusion: Meningococcal disease presents a stable pattern of endemic in our country. In our study serogroup B was the predominant and hegemonic in the last 5 years. Meningococcemia, age < 5 years, presence of shock, and Glasgow ≤1 2 purpuric syndrome (p = 0.02) were associated with greater severity. Continued vigilance is crucial to guide prevention strategies and control of meningococcal disease

Primera Red Sudamericana de Biomedicina. Investigación, educación y biotecnología aplicadas a la salud / [First South american network of biomedical research. Education and biotechnology for health].

It is in our interest, in this brief manuscript, to report the creation of the first program of regional integration of a network of research institutes in Biomedicine belonging to members of the MERCOSUR countries. We discuss some of the foundations that gave sustenance to its creation and its objectives in the medium and long term. In addition, we consider the potential of the results of this program in the fields of applied medical research, education and biotechnology.

[First South american network of biomedical research. Education and biotechnology for health]. / Primera Red Sudamericana de Biomedicina. Investigación, educación y biotecnología aplicadas a la salud.

It is in our interest, in this brief manuscript, to report the creation of the first program of regional integration of a network of research institutes in Biomedicine belonging to members of the MERCOSUR countries. We discuss some of the foundations that gave sustenance to its creation and its objectives in the medium and long term. In addition, we consider the potential of the results of this program in the fields of applied medical research, education and biotechnology.

Primera Red Sudamericana de Biomedicina. Investigación, educación y biotecnología aplicadas a la salud. / [First South american network of biomedical research. Education and biotechnology for health].

It is in our interest, in this brief manuscript, to report the creation of the first program of regional integration of a network of research institutes in Biomedicine belonging to members of the MERCOSUR countries. We discuss some of the foundations that gave sustenance to its creation and its objectives in the medium and long term. In addition, we consider the potential of the results of this program in the fields of applied medical research, education and biotechnology.

Correlación de serotipos, sensibilidad y resistencia antimicrobiana en niños con infecciones invasivas por Streptococcus pneumoniae en un centro de referencia de Asunción-Paraguay. Revisión de 6 años

Streptococcus pneumoniae is the main agent in extra-hospital pneumonia, meningitis in adults and acute otitis media in children. Aim: To determine the susceptibility, antibiotic resistance and serotypes of strains of S. pneumoniae isolated from patients admitted to the pediatric ward of the Institute of Tropical Medicine and correlate with the severe clinical picture presented. Results: We evaluated a total of 95 strains over a period of six years. 98% corresponded to samples from invasive infections. Of the 78 isolates, susceptibility testing was performed in 73 of them (94%) of which 37% (27/73) had decreased susceptibility to penicillin by Kirbi-Bauer method, 10% of the strains were resistant to erythromycin, tetracycline 12%, 59% to cotrimoxazole (trimethoprim-sulfamethoxazole) and 3% to chloramphenicol. We performed the minimum inhibitory concentration (MIC) to 69 strains (88%) where it was found highly resistant to penicillin in 13% (9 / 69), intermediate resistance in 6% (4/69) and cefotaxime resistance in 3 % of isolates. All strains tested were sensitive to vancomycin. It found 13 different serotypes. The 14, 5, 1 were common in all diseases studied. Conclusion: The strains of S. pneumoniae that have a higher percentage of resistance to penicillin belong to serotype 14 as well as strains with multidrug resistance. We isolated a single strain 23F to penicillin MIC 0.015 to 0.03 and cefotaxime

Streptococcus pneumoniae es el principal agente etiológico en la neumonía extra hospitalaria, la meningitis en adultos y la otitis media aguda en los niños. Objetivo: Determinar la susceptibilidad, la resistencia antibiótica y los serotipos de las cepas de S. pneumoniae aisladas de pacientes internados en el servicio de pediatría del Instituto de Medicina Tropical y correlacionarlos con la gravead del cuadro clínico que presentaron. Resultados: Se evaluaron un total de 95 cepas en un periodo de seis años. El 98% correspondieron a muestras procedentes de infecciones invasivas. De los 78 aislamientos, se realizó antibiograma en 73 de ellas (94%) de las cuales el 37% (27/73) tuvieron sensibilidad disminuida a la penicilina por el método de Kirbi-Bauer, el 10% de las cepas fueron resistentes a la eritromicina, el 12% a la tetraciclina, el 59% a cotrimoxazol (trimetroprim-sulfametoxazol) y el 3% al cloranfenicol. Se realizó la concentración inhibitoria mínima (CIM) a 69 cepas (88%) en donde se halló alta resistencia a la Penicilina en 13% (9/69), resistencia intermedia en 6% (4/69) y resistencia a cefotaxima en 3% de los aislamientos. Todas las cepas estudiadas fueron sensibles a la vancomicina. Se encontraron 13 serotipos diferentes. Los serotipos 14, 5, 1 fueron los más frecuentes en todas las patologías estudiadas. Conclusión: Un sostenido incremento en la resistencia a antibióticos del Streptococcus pneumoniae se ha observado en un centro hospitalario de referencia. Algunos serotipo del neumococo muestran asociación significativa con resistencia. Es mandatoria la vigilancia continua de la sensibilidad de cepas de S. pneumoniae.

Comparación de sensibilidad a los antimicrobianos por método de difusión y dilución en Agar frente a ciprofloxina y eritromicina en aislamiento de Campylobacter spp / Comparison of sensitivity to the antimicrobials by diffusion method and dilution in Agar against ciprofloxina and eritromicina in isolation of Campylobacter

Estudio prospectivo, comparativo, realizado en el Laboratorio Central de Salud Pública (LCSP). Se incluyó en el estudio 58 cepas de Campylobacter spp., aisladas de heces humanas y que fueron remitidas de diferentes centros sanitarios al LCSP. Estudia la sensibilidad de la Ciprofloxicina (IP) y Eritromicina (ERY) por 2 métodos: el método de difusión de Kirby- Bauer y siguiendo recomendaciones del Clinical and Laboratory Standards Institute y el método de dilución en agar (macrodilución), utilizando el multi-inoculador de Steer.Para el análisis de la correlación utilizamos el scatter plot y el porcentaje de concordancia

Perfil de resistencia de estafilococo coagulasa negativo aislados de muestras de hemocultivos ene el Laboratorio Central de Salud Pública, periodo 2006-2008 / Negative profile of resistance of estafilococo coagulasa isolated of samples of hemocultures ene the Central Laboratory of Public Health, period 2006-2008

Estudio observacional descriptivo de carácter retrospectivo, comprendido en el periodo 2006 al 2008 de todo los hemocultivos procesados en el Laboratorio Central de Salud Pública de Paraguay con aislamiento de Estafilococos Coagulasa-Negativos (ECN). El antibiograma se realizó empleando el método de Kirby-Bauer y siguiendo recomendaciones del Clinical and Laboratory Standards Institute (CLSI)

Laboratory-based surveillance of Streptococcus pneumoniae invasive disease in children in 10 Latin American countries: a SIREVA II project, 2000-2005.

BACKGROUND: For the last 14 years the Pan American Health Organization has been promoting surveillance of invasive pneumococcal disease in Latin American children for better understanding of the disease tendencies regarding capsular types circulation in each country and susceptibility to antimicrobials. METHODS: Laboratory-based surveillance data from 10 Latin American countries collected from 2000 to 2005 were analyzed, including serotype distribution and susceptibility to beta-lactam antibiotics. RESULTS: Although 61 different capsular types were identified during the 6-year surveillance, 13 serotypes accounted for 86% of all isolates. These were consistently the most prevalent throughout the study period with serotype 14 predominating. Diminished susceptibility to penicillin was detected in 38% of all Streptococcus pneumoniae isolates, with the highest prevalence in Dominican Republic and Mexico. Decreased susceptibility to penicillin increased in Brazil and Colombia whereas decreased high resistance rates was recorded in Chile. CONCLUSIONS: These data indicate that 10 countries of the Region continue to have high quality laboratory-based surveillance for pneumococcal disease thus generating valuable information so that healthcare decision makers may prioritize interventions. The heptavalent vaccine will potentially cover from 52.4% to 76.5% of strains causing invasive pneumococcal disease and the 13 valent from 76.7% to 88.3%.