Changes in the incidence of acute bacterial meningitis caused by Streptococcus pneumoniae and the implications of serotype replacement in children in Colombia after mass vaccination with PCV10.

Introduction: Acute bacterial meningitis (ABM) is a public health problem. The disease has reemerged after the introduction of pneumococcal conjugate vaccines (PCVs) due to an increase in serotypes that are not covered. The objective was to determine the changes in the disease incidence before and after the introduction of the 10-valent vaccine (PCV10) in Colombia. Methods: This multicenter study was conducted in 17 hospitals in Colombia. Data were collected from January 2008 to December 2019 in 10 hospitals in Bogotá and from January 2017 to December 2019 in seven hospitals in Cali, Medellín and Cartagena. The data were grouped into three periods: 2008-2011, 2012-2015, and 2016-2019. Results: Of the 706 cases of invasive pneumococcal disease, 81 (11.4%) corresponded to meningitis. The relative incidence in Bogotá in the first period was 0.6 per 100,000 patients ≤ 5 years, decreased to 0.4 per 100,000 patients ≤ 5 years in the second period and increased in the third period to 0.7 per 100,000 patients ≤ 5 years. Serotypes covered by PCV10 decreased from 75 to 9.1%, with Spn19A (31.8%) and Spn34 (13.6%) emerging in the third period. Increased resistance to penicillin (13 to 37%) and to ceftriaxone (5.9 to 16%) was due to the emergence of multidrug-resistant Spn19A. The total mortality rate was 23.5% and increased from 12 to 33%. Conclusions: ABM due to pneumococcus has high morbidity and mortality rates. Reemergence of the disease has been observed due to the inclusion of polymerase chain reaction (PCR) for diagnosis and replacement of circulating serotypes after the introduction of PCV10, with an increase in Spn19A, which causes death and exhibits antimicrobial resistance. Continued surveillance is needed.

Clonal Distribution and Antibiotic Susceptibility of Staphylococcus aureus from Pediatric Patients: 8-Year Trends in a Children's Hospital in Colombia.

Emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains in healthcare settings has changed the hospital epidemiology of MRSA in the last few years. Despite a global increase in MRSA frequency, infections caused by methicillin-susceptible S. aureus (MSSA) have persisted in healthcare settings and the community. Staphylococcus aureus isolates were collected between 2009 and 2017 at the Children's Hospital of a Caribbean city in South America. Methicillin-resistant isolates were subjected to SCCmec typing. Representative isolates were analyzed by multilocus sequence typing (MLST) and spa typing. Antibiotic susceptibility was assessed by agar dilution method. D-zone test was performed in erythromycin-resistant isolates to determine macrolide/lincosamide/streptogramin resistance. Spa typing revealed 10 different spa types. The main epidemic clones circulating during the study period were: ST8-MRSA-IVc, ST923-MRSA-IVa and ST8-MRSA-IVa. The study found high frequencies of PVL genes and resistance to erythromycin and clindamycin in the isolates. This study provides the first description of the population structure of MRSA and MSSA causing infections attended in the participating Children's Hospital. ST8-MRSA-IVc, ST923-MRSA-IVa and ST8-MRSA-IVa were the most prevalent in the isolate population.

This study was aimed to determine the distribution of sequence types, SCCmec types and antibiotic resistance profiles of MRSA and MSSA isolates recovered from pediatric patients with clinical infections attended in the Children's Hospital of a Caribbean city in South America in a period spanning 8 years. We found high frequencies of PVL genes and resistance to erythromycin and clindamycin in the isolates. The fact that MRSA and MSSA isolates in this study were frequently resistant to erythromycin and clindamycin is an indication of the selective pressure imposed by the extensive use of these two antibiotics in the treatment of skin and soft tissue infections in the geographical area of this study. This is the first study reporting the clonal distribution of Staphylococcus aureus causing infections in the pediatric population of Cartagena, a tropical city in the Caribbean coast of Colombia.

Microcefalia por Zika un problema latente: Reporte de Caso y Aspectos Moleculares / Zika microcephaly a latent problem: Case Report and Molecular Aspects

Se presenta el caso de un paciente de 20 días de nacido, procedente de Cartagena (Bolívar), hospitalizado por presentar fiebre de 6 días de evolución asociado a sintomatología respiratoria con evaluación neurológica normal. La ecografía obstétrica evidenció una microcefalia con un percentil de perímetro cefálico <2, con hipoplasia del cuerpo calloso y tomografía axial computarizada de cráneo que reportó diámetros cefálicos disminuidos, finas calcificaciones residuales en región frontal-parietal y cambios atróficos cerebrales subcorticales. Se le inició terapia antibiótica por presentar sepsis neonatal, las pruebas serológicas y la PCR para Zika resultaron positivas. Se decidió dar el alta médica al 6 día por mejoría clínica y no presentar déficit neurológico aparente. Aunque no existe un tratamiento específico, el pilar del manejo de un recién nacido con microcefalia es el seguimiento y la vigilancia futura de las posibles comorbilidades, como epilepsia, parálisis cerebral o retraso cognitivo y motor.

We present the case of a 20-day-old patient from Cartagena (Bolívar), hospitalized for presenting a 6-day fever associated with respiratory symptoms with normal neurological evaluation. The obstetric ultrasound showed a microcephaly with a percentile of cephalic perimeter <2, with hypoplasia of the corpus callosum and computed tomography of the skull that reported decreased cephalic diameters, fine residual calcifications in the frontal-parietal region and atrophic subcortical cerebral changes. Antibiotic therapy was initiated due to neonatal sepsis, the serological tests and the PCR for Zika were positive. It was decided to discharge the hospital after 6 days due to clinical improvement and for not presenting apparent neurological deficit. Although there is no specific treatment, the pillar of the management of a newborn with microcephaly is the monitoring and future surveillance of possible comorbidities, such as epilepsy, cerebral palsy or cognitive and motor retardation.

Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014.

Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. This study aimed to determine the genetic diversity and phylogenetic relationships of CHIKVs in Colombia. A descriptive and retrospective study was carried out using sera of patients infected with Chikungunya during the outbreak in Colombia. The whole genomes of CHIKV (n = 16) were sequenced with an Illumina Hi-seq 2500 and were assembled using the Iterative Virus Assembler software. A Bayesian inference phylogenetic analysis was carried out with 157 strains of worldwide origin. The Colombian CHIKV sequences were grouped in the Asian genotype; however, three independent phylogenetic subclades were observed, probably the result of three separate introductions from Panama, Nicaragua, and St. Barts. Each subclade showed several different non-synonymous mutations (nsP2-A153V; nsp2-Y543H; nsp2-G720A; nsP3-L458P; Capside R78Q), that may have functional consequences for CHIKV biology and pathogenesis. These same mutations may affect the efficacy of potential CHIKV vaccines.

Malaria congénita por Plasmodium vivax: reporte de caso / Congenital malaria by Plasmodium vivax: case report

Resumen Se describe el caso de malaria congénita por Plasmodium vivax de un neonato de 25 días de nacido, el cual consulta por fiebre e ictericia persistente. La sospecha inicial orientaba a un diagnóstico de sepsis neonatal. El neonato residente en Cartagena (Colombia), presentaba antecedente perinatal de ictericia y antecedente materno de malaria gestacional diagnosticada al cuarto mes. La madre refirió haber vivido los primeros siete meses de su embarazo en Tierralta, Córdoba (Colombia), la cual es una zona endémica de malaria. Posterior a los resultados del extendido de sangre periférica del neonato se demostró la presencia de Plasmodium vivax. El tratamiento antimalárico fue realizado con cloroquina, con eficaz mejoría clínica. Se destaca la importancia de tener a la malaria congénita como diagnóstico diferencial en infecciones neonatales, sepsis, fiebre inexplicable o en lactantes que presenten anemia hemolítica, ictericia y hepatoesplenomegalia en pacientes provenientes de zonas endémicas de malaria.

Abstract We describe the case of congenital malaria by Plasmodium vivax of a neonate of 25 days of age, who consults for fever and persistent jaundice. The initial suspicion aimed to a diagnosis of neonatal sepsis. The neonate living in Cartagena (Colombia) had a perinatal history of jaundice and a maternal history of gestational malaria diagnosed at the fourth month. The mother reported having lived the first seven months of her pregnancy in Tierralta, Córdoba (Colombia), which is an endemic area of malaria. Subsequent to the results of the peripheral blood smear of the neonate, the presence of Plasmodium vivax was demonstrated. The antimalarial treatment was performed with chloroquine, with effective clinical improvement. The importance of having congenital malaria as a differential diagnosis in neonatal infections, sepsis and unexplained fever or in infants with hemolytic anemia, jaundice and hepatosplenomegaly in patients from malaria endemic areas is highlighted.

Emergence and spread of a new community-genotype methicillin-resistant Staphylococcus aureus clone in Colombia.

BACKGROUND: Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) clones are a global concern due to their resistance and increased virulence and their ability to cause infections both hospitalized patients and healthy people in the community. Here, we characterize 32 isolates of a new CG-MRSA clone. These isolates were identified in four cities in Colombia, South America. METHODS: The isolates were recovered from four different epidemiological and prospective studies that were conducted in several regions of Colombia. Molecular characterizations included multilocus sequence typing; pulsed-field gel electrophoresis; SCCmec, agr and spa typing; and whole-genome sequencing. RESULTS: All isolates belonged to ST923 (clonal complex 8), harbouring SCCmec IVa and a spa type t1635 and lacking an arginine catabolism mobile element. The isolates were classified as COL923, were resistant to at least one non-beta-lactam antibiotic, and exhibited high frequencies (>60%) of resistance to macrolides and tetracycline. Using whole-genome sequencing, we found that this new clone harbours novel prophage 3 and beta-island structures and a slightly different pathogenicity island 5. Moreover, isolates belonging to the COL923 clone are grouped in a different clade than USA300 and USA300-LV. CONCLUSION: Our results show the emergence and spread of the COL923 clone in different cities in Colombia. This clone is resistant to several antibiotics and possesses new structures in its mobile genetic elements.

A systematic review of observational studies on oxidative/nitrosative stress involvement in dengue pathogenesis.

OBJECTIVE: Our objective was to systematically review the published observational research related to the role of oxidative-nitrosative stress in pathogenesis of dengue. METHODS: We searched electronic databases (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) using the term: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide, and nitric oxide synthase. Articles were selected for review by title and abstract excluding letter, review, in vivo and in vitro studies, and duplicates studies. Selected articles were reviewed for study design, original purposes, sample size, main outcomes, methods, and oxidative-nitrosative stress markers values. RESULTS: In total, 4,331 non-duplicates articles were identified from electronic databases searches, of which 16 were eligible for full text searching. Data from the observational studies originate from Asian countries (50%; 8/16), South American countries (31.2%; 5/16), and Central America and the Caribbean countries (18.8%; 3/16). Case-control study was the type of design most common in researches reviewed. The 1997 World Health Organization (WHO) dengue case classification criteria were used in all studies included in this review. CONCLUSIONS: Based on published data found in peer-reviewed literature, oxidative and nitrosative stress are demonstrated by changes in plasma levels of nitric oxide, antioxidants, lipid peroxidation and protein oxidation markers in patients with dengue infection. Additionally, elevated serum protein carbonyls and malondialdehyde levels appear to be associated with dengue disease severity.

OBJETIVO: Sistematizar las evidencias observacionales sobre la relación entre el estrés oxidativo-nitrosativo y la patogénesis del dengue. MÉTODOS: Revisión sistemática de estudios observacionales en las bases de datos (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) utilizando las siguientes palabras clave: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide y nitric oxide synthase. La selección inicial fue realizada a partir del título y resumen excluyéndose: cartas para editor, revisiones, estudios in vivo/in vitro y duplicados. A cada artículo seleccionado, se le revisó el diseño del estudio, objetivo, tamaño de la muestra, resultados principales y niveles plasmáticos de los marcadores de estrés oxidativo-nitrosativo. RESULTADOS: De 4,331 publicaciones encontradas, 16 estudios cumplieron con los criterios de inclusión. El 50 % (8/16) de los estudios revisados fueron realizados en países de Sur América, Centro América y del Caribe. El diseño de casos y controles fue el más frecuente. El anterior sistema de clasificación de casos (OMS-1997) fue utilizado en todos los estudios incluidos en esta revisión. CONCLUSIONES: El estrés oxidativo-nitrosativo se encuentra presente en el curso de la infección por virus dengue, demostrado por los cambios en las concentraciones plasmáticas de óxido nítrico, antioxidantes y marcadores de lipoperoxidación y de oxidación de proteínas. Por último, parece existir una asociación entre la elevación de los niveles plasmáticos de los carbonilos proteicos y malondialdehído con la severidad del dengue.

Outbreak of Chikungunya virus in the north Caribbean area of Colombia: clinical presentation and phylogenetic analysis.

INTRODUCTION: The Caribbean area of Colombia has been severely affected by a Chikungunya virus (CHIKV) outbreak since 2014. METHODOLOGY: The study was carried out on 100 patients during a fever outbreak from August to September 2014 in two small rural villages in the northern Caribbean area of Colombia. The molecular assays performed by reverse transcription polymerase chain reaction (RT-PCR) on acute patient sera were collected within one to five days of the appearance of symptoms. Sequence analyses were carried out based on phylogenetic analyses of genes NS1 and E2. For serological assays, 49 (49%) patients at ≥ 6 days of disease onset were tested with NovaLisa Chikungunya IgG/IgM µ-capture enzyme-linked immunosorbent assay (ELISA). RESULTS: The main signs or symptoms associated with Chikungunya infection were arthralgia of the lower limbs (96%), fever (91%), arthralgia of the upper limbs (85%), rash (64%), and headache (57%). Ninety-four percent (46/49) of patients were positive for either IgM or IgG; the remaining three (6%) patients were seronegative. Viral loads were detected in 25 patients. Based on phylogenetic analysis of NS1 and E2, the characterization of the Colombian CHIKV indicated that it was a strain closely related to the British Virgin Islands strain and to the Asian genotype. CONCLUSIONS: This study shows the phylogenetic and clinical description of CHIKV in Colombia. The main symptoms shown were: arthralgia, fever, and rash. CHIKV sequences detected in Colombian patients were within the Asian genotype and closely related to the British Virgin Islands strain.

A systematic review of observational studies on oxidative/nitrosative stress involvement in dengue pathogenesis / Revisión sistemática de los estudios observacionales sobre el papel del estrés oxidativo-nitrosativo en la patogénesis del dengue

Objective: Our objective was to systematically review the published observational research related to the role of oxidative-nitrosative stress in pathogenesis of dengue. Methods: We searched electronic databases (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) using the term: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide, and nitric oxide synthase. Articles were selected for review by title and abstract excluding letter, review, in vivo and in vitro studies, and duplicates studies. Selected articles were reviewed for study design, original purposes, sample size, main outcomes, methods, and oxidative-nitrosative stress markers values. Results: In total, 4,331 non-duplicates articles were identified from electronic databases searches, of which 16 were eligible for full text searching. Data from the observational studies originate from Asian countries (50%; 8/16), South American countries (31.2%; 5/16), and Central America and the Caribbean countries (18.8%; 3/16). Case-control study was the type of design most common in researches reviewed. The 1997 World Health Organization (WHO) dengue case classification criteria were used in all studies included in this review. Conclusions: Based on published data found in peer-reviewed literature, oxidative and nitrosative stress are demonstrated by changes in plasma levels of nitric oxide, antioxidants, lipid peroxidation and protein oxidation markers in patients with dengue infection. Additionally, elevated serum protein carbonyls and malondialdehyde levels appear to be associated with dengue disease severity.

Objetivo: Sistematizar las evidencias observacionales sobre la relación entre el estrés oxidativo-nitrosativo y la patogénesis del dengue. Métodos: Revisión sistemática de estudios observacionales en las bases de datos (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) utilizando las siguientes palabras clave: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide y nitric oxide synthase. La selección inicial fue realizada a partir del título y resumen excluyéndose: cartas para editor, revisiones, estudios in vivo/in vitro y duplicados. A cada artículo seleccionado, se le revisó el diseño del estudio, objetivo, tamaño de la muestra, resultados principales y niveles plasmáticos de los marcadores de estrés oxidativo-nitrosativo. Resultados: De 4,331 publicaciones encontradas, 16 estudios cumplieron con los criterios de inclusión. El 50% (8/16) de los estudios revisados fueron realizados en países de Sur América, Centro América y del Caribe. El diseño de casos y controles fue el más frecuente. El anterior sistema de clasificación de casos (OMS-1997) fue utilizado en todos los estudios incluidos en esta revisión. Conclusiones: El estrés oxidativo-nitrosativo se encuentra presente en el curso de la infección por virus dengue, demostrado por los cambios en las concentraciones plasmáticas de óxido nítrico, antioxidantes y marcadores de lipoperoxidación y de oxidación de proteínas. Por último, parece existir una asociación entre la elevación de los niveles plasmáticos de los carbonilos proteicos y malondialdehído con la severidad del dengue.

[Cerebrovascular hemorrhage associated with acquired cytomegalovirus infection in an infant]. / Hemorragia cerebrovascular asociada con infección por citomegalovirus en un lactante menor.

Cytomegalovirus is the most frequent causative agent of perinatal infection and a major cause of acquired viral infections. This case report aims to show the broad clinical spectrum of the presentation of cytomegalovirus infection. The correct classification of congenital or acquired infection and its prompt treatment can prevent complications and sequelae in severe cases. We report the case of an infant with acquired cytomegalovirus infection, which presented an unusual feature of cerebral hemorrhage. The patient was treated with ganciclovir, with a favorable evolution of the clinical symptoms. Cytomegalovirus infection is common in children, both in its congenital and acquired forms. Acquired infection, as portrayed in this case, is mainly characterized by hematological compromise given by the marked thrombocytopenia, which may rarely result in cases of bleeding in the central nervous system. In this patient, no important clinical implications occurred. In addition, most of the acquired infections are self-limited and require no treatment.

Hemorragia cerebrovascular asociada con infección por citomegalovirus en un lactante menor / Cerebrovascular hemorrhage associated with acquired cytomegalovirus infection in an infant

El citomegalovirus es el agente de infección perinatal más frecuente y una de las principales causas de infecciones virales adquiridas. En la presentación del siguiente caso se describe el amplio espectro clínico de la infección por citomegalovirus. La clasificación correcta de la infección como congénita o adquirida y el tratamiento oportuno pueden evitar complicaciones y secuelas en los casos graves. Se describe el caso de un lactante menor que presentaba una infección por citomegalovirus con la manifestación poco frecuente de hemorragia cerebral. Después del tratamiento con ganciclovir, los síntomas clínicos evolucionaron favorablemente. La infección por citomegalovirus es muy frecuente en la edad pediátrica, tanto en la forma congénita como en la adquirida. La forma adquirida, como la de este caso, se caracteriza principalmente por el compromiso hematológico, al producirse una importante trombocitopenia, lo que puede originar, aunque infrecuentemente, sangrado del sistema nervioso central; la mayoría de las infecciones adquiridas, sin embargo, son de resolución espontánea y no requieren tratamiento. En este paciente no se presentaron repercusiones clínicas de importancia.

Cytomegalovirus is the most frequent causative agent of perinatal infection and a major cause of acquired viral infections. This case report aims to show the broad clinical spectrum of the presentation of cytomegalovirus infection. The correct classification of congenital or acquired infection and its prompt treatment can prevent complications and sequelae in severe cases. We report the case of an infant with acquired cytomegalovirus infection, which presented an unusual feature of cerebral hemorrhage. The patient was treated with ganciclovir, with a favorable evolution of the clinical symptoms. Cytomegalovirus infection is common in children, both in its congenital and acquired forms. Acquired infection, as portrayed in this case, is mainly characterized by hematological compromise given by the marked thrombocytopenia, which may rarely result in cases of bleeding in the central nervous system. In this patient, no important clinical implications occurred. In addition, most of the acquired infections are self-limited and require no treatment.