Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis.

RATIONALE: Current immunodiagnostic tests for tuberculosis (TB), including the tuberculin skin test and IFN-γ release assay (IGRA), have significant limitations, which include their inability to distinguish between latent TB infection (LTBI) and active TB, a distinction critical for clinical management. OBJECTIVES: To identify mycobacteria-specific cytokine biomarkers that characterize TB infection, determine their diagnostic performance characteristics, and establish whether these biomarkers can distinguish between LTBI and active TB. METHODS: A total of 149 children investigated for TB infection were recruited; all participants underwent a tuberculin skin test and QuantiFERON-TB Gold assay. In parallel, whole-blood assays using early secretory antigenic target-6, culture filtrate protein-10, and PPD as stimulatory antigens were undertaken, and cytokine responses were determined by xMAP multiplex assays. MEASUREMENTS AND MAIN RESULTS: IFN-γ, interferon-inducible protein-10 (IP-10), tumor necrosis factor (TNF)-α, IL-1ra, IL-2, IL-13, and MIP-1ß (macrophage inflammatory protein-1ß) responses were significantly higher in LTBI and active TB cases than in TB-uninfected individuals, irrespective of the stimulant. Receiver operating characteristic analyses showed that IP-10, TNF-α, and IL-2 responses achieved high sensitivity and specificity for the distinction between TB-uninfected and TB-infected individuals. TNF-α, IL-1ra, and IL-10 responses had the greatest ability to distinguish between LTBI and active TB cases; the combinations of TNF-α/IL-1ra and TNF-α/IL-10 achieved correct classification of 95.5% and 100% of cases, respectively. CONCLUSIONS: We identified several mycobacteria-specific cytokine biomarkers with the potential to be exploited for immunodiagnosis. Incorporation of these biomarkers into future immunodiagnostic assays for TB could result in substantial gains in sensitivity and allow the distinction between LTBI and active TB based on a blood test alone.

Pneumococcal disease: new challenges and new proposals for Latin America.

Invasive pneumococcal disease (IPD) is the leading cause of vaccine preventable deaths in children < 5 years worldwide and it causes a significant disease burden in Latin America and the Caribbean. In order to combat the increasing incidence of IPD in our region, the vast majority of countries have included pneumococcal vaccines as a preventive strategy. The GREEN group (Grupo Regional de Estudio de la Enfermedad Neumococica) has been created to study pneumococcal disease, unify data from the Latin American countries and learn in detail the epidemiology pre and post-pneumococcal vaccination.

Epidemiology of pertussis in Costa Rica and the impact of vaccination: A 58-year experience (1961-2018).

Costa Rica is an upper middle-income country in Central America with a vigorous public health system. We have studied the number of cases, hospitalizations, and deaths due to pertussis from 1961 to 2018, in relation to vaccine coverage. Following the introduction of the fourth and fifth doses of DTP (booster doses) in 1973 there was a marked reduction of reported pertussis. In 2002 pertussis surveillance and laboratory diagnosis were improved. In 2007, Tdap post-partum immunization was introduced and then switched to intrapartum Tdap immunization in 2011. Of these two strategies post-partum vaccination seemed to have a greater effect in decreasing hospitalizations and deaths, nevertheless, since 2011 there has been only 4 infant deaths due to pertussis.

Multisystem Inflammatory Syndrome in Children in Western Countries? Decreasing Incidence as the Pandemic Progresses?: An Observational Multicenter International Cross-sectional Study.

BACKGROUND: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study. METHODS: This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogotá (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)]. RESULTS: We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month ( P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend ( P < 0.001), but this ratio was not statistically significant for the rest of sites. CONCLUSIONS: To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases.

Epidemiology, Etiology and Clinical Aspects of Childhood Acute Encephalitis in a Tertiary Pediatric Hospital in Costa Rica.

BACKGROUND: Limited data are available on childhood encephalitis in Latin America. Our study aimed to increase insight on clinical presentation, etiology and outcome of children with acute encephalitis in Costa Rica. METHODS: We conducted a prospective, observational study during an 8-month period at the Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera" in Costa Rica. Case definition was according to "International Encephalitis Consortium" in children <13 years. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. RESULTS: Forty patients were identified. Mean age was 5 years and 57.5% were male. Most frequently neurologic symptoms were altered mental status (100.0%), headache (57.5%) and seizures (52.5%). Etiology was determined in 52.5% of cases. Probable or confirmed viral etiology was identified in 6 cases (15.0%) and bacterial etiology in also 6 cases (15.0%). A possible etiology was identified in 7 cases (17.5%). Autoimmune encephalitis was diagnosed in 2 patients (5.0%). Enterovirus and Streptococcus pneumoniae were the most common confirmed agents. No cases of herpes simplex virus were found. Etiology of 19 cases (47.5%) remained unknown. Sequelae were reported in 45.0% of patients. Mortality rate was 15.0% (6 cases), 3 caused by virus (adenovirus, human herpesvirus 6, enterovirus), 2 by bacteria (S. pneumoniae, Haemophilus influenzae type b) and 1 of unknown etiology. Diffuse cerebral edema was the most important mortality predictor (P < 0.001). CONCLUSIONS: Acute encephalitis in our study was associated with significant morbidity and mortality. Early and aggressive antiviral, antibiotic and anticerebral edema treatment is necessary when acute encephalitis is suspected.

Long-term sequelae secondary to snakebite envenoming: a single centre retrospective study in a Costa Rican paediatric hospital.

OBJECTIVES: Although devastating acute effects associated with snake envenoming are well described, the long-term sequelae resulting from these envenomings have not been adequately addressed, especially in the paediatric population. The aim of our study is to describe the clinical characteristics among paediatric patients in Costa Rica who developed long-term sequelae secondary to snakebite envenoming. DESIGN: Retrospective descriptive study of paediatric patients under 13 years who were admitted with a history of a recent snakebite at the National Children's Hospital in Costa Rica from January 2001 to December 2014. RESULTS: We enrolled 74 patients admitted to our centre due to envenoming, and separated those who did not develop sequelae (50 patients) from those who did (24 patients). Of those who presented acute complications during hospitalisation, local wound infection and clinically diagnosed compartmental syndrome were significantly higher in the group that developed sequelae thereafter. Hypertrophic scars (66.7%), functional limitation of affected limb (37.5%) and the need of skin graft (37.5%) were the most common sequelae. The median follow-up of patients with long-term sequelae after discharge was 25.4 months (5.6-59.4). No deaths were reported during this time period. CONCLUSIONS: Given the high economic, personal and healthcare burden that entails follow-up of these patients, efforts should be carried out to prevent the factors associated with sequelae among the affected population.

Bacterial Infections Associated with Viperidae Snakebites in Children: A 14-Year Experience at the Hospital Nacional de Niños de Costa Rica†.

Secondary bacterial infections following Viperidae snakebite envenomation in children are common. Among 75 patients admitted because of snakebites at the only pediatric hospital in Costa Rica, 16 (21.3%) had a culture-confirmed secondary bacterial infection. Morganella morganii (37.5%), Aeromonas hydrophila (31.2%), and Providencia rettgeri (18.7%) were the most common pathogens. Empiric prophylaxis is still recommended and should be based on local etiological agents and antimicrobial susceptibilities.

[Epidemiology of dengue in Central America and the Dominican Republic]. / Epidemiología del dengue en Centroamérica y República Dominicana.

BACKGROUND: Central America experiences a high burden of dengue reporting about 8% of all cases in the continent. This work reports the epidemiology of dengue in the sub region in a 10 years period. AIM: To describe the epidemiology of dengue in Central America and the Dominican Republic. METHODS: Study period from 2005 to 2014. The data on dengue cases and deaths of the countries of Central America and the Dominican Republic, reported by the Ministries of Health, were compiled and analyzed and corroborated with the data published in the online bulletins and the interactive database of the Pan American Health Organization (PAHO). Population statistics were obtained from the National Statistics and Census Institutes of each country. RESULTS: During the study period, 1,118,464 cases of dengue were notified. There were 32,431 serious cases reported, 888 people died. The lethality per case of dengue was on average 0.08%. The four dengue serotypes circulated during the decade analyzed. DISCUSSION: Clinical and epidemiological information indicates high incidence rates, which have fluctuated in recent years, with significant co-circulation of several serotypes at the same time. CONCLUSIONS: Notorious surveillance data collection differences were identified between countries, determining a heterologous epidemiological pattern.

Snakebite envenoming in children: A neglected tropical disease in a Costa Rican pediatric tertiary care center.

BACKGROUND: Introduced in June 2017 by the World Health Organization (WHO) as a Neglected Tropical Diseases, snakebite envenoming is a global health problem. In Costa Rica, an incidence of 15 per 100,000 inhabitants and a mortality rate of 0.15 per 100,000 inhabitants per year were reported from 2005-2012. Children are also affected and prone to complications. METHODS: Retrospective descriptive 14-year study of children with envenomings by Viperidae snakebites managed at the tertiary pediatric hospital in Costa Rica. FINDINGS: 80 patients (pts) were included and classified as having mild (17 pts, 29.3%), moderate (58 pts, 72.5%) or severe (5 pts, 6.2%) envenoming. 52/80 (65%) patients received treatment within the first four hours, three (3.75%) between 5-8 h, three between 9-12 h, four (4%) between 13-16 h, two (2.5%) between 17-20 h, and seven (8.75%) after 20 h. Edema was documented in 76/80 (95%), pain in 58 (72.5%), local bleeding in 23 (28.8%), emesis in 10 (12.5%), bullae formation in 8 (10%), and tissue necrosis in three (3.8%) pts. Complications presented according with degree of envenoming, being more common in severe cases: wound infection occurred in 14/58 (24.1%) with moderate envenoming and 5/5 pts with severe envenoming (p < 0.0001), bleeding presented in 3/58 (5.2%) with moderate cases, and 2/5 (40%) in pts with severe envenoming (p = 0.004); and compartmental syndrome occurred in 3/17 (17.6%) pts with mild envenoming, in 33/58 (56.9%), and 5/5 of moderate and severe envenomed pts, respectively (p = 0.0014). Sequelae were documented 25/80 (31%).

Pustular rash in Kawasaki syndrome.

The skin rash of Kawasaki syndrome is usually erythematous. A 23-month-old Costa Rican boy was admitted with a clinical picture compatible with Kawasaki syndrome, except for his skin lesions. He had diffuse, confluent, multiple sterile whitish pustular lesions on his chest, abdomen, neck, genitals, and thighs.

Varicella prevention in Costa Rica: impact of a one-dose schedule universal vaccination.

INTRODUCTION: To describe the impact following a 1-dose Varicella vaccination schedule introduced in Costa Rica in September 2007. Areas covered: This is a retrospective review using epidemiologic surveillance national databases of varicella cases and hospitalizations, period 2000-2015. We analyzed age-related varicella incidence cases and hospitalization trends before and after the vaccine introduction. Expert commentary: Varicella vaccine coverage among children 16 months age increased from 76% in 2008 to 95% in 2015. During this period Costa Rica reached a 73.8% reduction of Varicella reported cases and 85.9% reduction of hospitalizations in the general population. Among children under 5 years of age, that reduction was 79.1% and 87%, respectively. Varicella complications in hospitalized patients decreased 98%, from n = 53 in 2008 to n = 1 in 2014. After 8-years post implementation of a 1-dose schedule of universal varicella vaccination, a dramatic overall disease reduction in incidence, hospitalizations and complicated cases has been observed in all age groups.

[Kikuchi-Fujimoto disease in pediatric population: a case report and a review of literature]. / Enfermedad de kikuchi-fujimoto en pediatría. Reporte de un caso y revisión de la literatura.

A 10 year-old child, with a history of a right cervical mass, is admitted to the Costa Rican National Children's Hospital for workup. The mass appeared approximately 4 weeks before admission. Laboratory tests were performed and malignity, infection and immunologic causes were ruled out. A biopsy was performed revealing granulomas characterized by central necrosis with abundant karyorrhexis, surrounded by histiocytes, lymphocytes and giant multinucleated cells, without neutrophils. Special stains showed no microorganisms. Once infectious and immunologic causes were excluded, and based on the biopsy's result, treatment was ruled out. Twelve months later, the patient is still asymptomatic; therefore, the diagnosis of a Kikuchi-Fujimoto syndrome was proposed. This report constitutes the first pediatric case diagnosed in our country.

Measles outbreaks: what does it represent for the elimination strategy in the region of the Americas? A call for the action.

The US is experiencing a large multi-state measles outbreak that started in California in 2014. At this time, no source case for the outbreak has been identified. Measles was declared eliminated in the US in 2000, because at that time, there were high coverage rates with the two-dose schedule and these vaccines have been very immunogenic. Measles is still endemic in many parts of the world, and outbreaks can occur when unvaccinated groups are exposed to imported measles virus. The current multi-state outbreak underscores the ongoing risk of measles importation, the need for high measles vaccination coverage rates, and the importance of a prompt and appropriate public health response to individual cases and outbreaks. The US outbreak threatens measles control in the Americas. Strengthening immunization programs and keeping vaccination coverage rates above 95% with a two-dose schedule will be necessary for measles control strategies in the Americas.

Epidemiología del dengue en Centroamérica y República Dominicana / Epidemiology of dengue in Central America and the Dominican Republic

Resumen Introducción: Centroamérica experimenta una alta carga de la enfermedad por dengue aportando cerca de 8% de todos los casos del continente. Este trabajo reporta la epidemiología del dengue en la subregión en un período de 10 años. Objetivos: Documentar la epidemiología del dengue en Centro América y República Dominicana. Material y Métodos: Período de estudio: años 2005-2014. Se recopilaron y analizaron los datos de casos y muertes por dengue de los países de Centro América y República Dominicana, reportados por los Ministerios de Salud y se corroboró con los datos publicados en los boletines en línea y la base de datos interactiva de la Organización Panamericana de la Salud (OPS). Se obtuvieron estadísticas poblacionales de los Institutos Nacionales de Estadística y Censo de cada país. Resultados: Durante el período de estudio fueron notificados 1.118.464 casos de dengue. Reportados 32.431 casos graves, 888 personas fallecidas. La letalidad por caso de dengue fue en promedio 0,08%. Los cuatro serotipos de dengue circularon durante el decenio estudiado. Discusión: La información clínica y epidemiológica, indica tasas de incidencia alta, que han fluctuado en los últimos años, con co-circulación significativa de varios serotipos a la vez. Conclusiones: Se identificaron diferencias notorias en la recolección de datos de la vigilancia entre países. Se determinó un patrón epidemiológico heterogéneo.

Background: Central America experiences a high burden of dengue reporting about 8% of all cases in the continent. This work reports the epidemiology of dengue in the sub region in a 10 years period. Aim: To describe the epidemiology of dengue in Central America and the Dominican Republic. Methods: Study period from 2005 to 2014. The data on dengue cases and deaths of the countries of Central America and the Dominican Republic, reported by the Ministries of Health, were compiled and analyzed and corroborated with the data published in the online bulletins and the interactive database of the Pan American Health Organization (PAHO). Population statistics were obtained from the National Statistics and Census Institutes of each country. Results: During the study period, 1,118,464 cases of dengue were notified. There were 32,431 serious cases reported, 888 people died. The lethality per case of dengue was on average 0.08%. The four dengue serotypes circulated during the decade analyzed. Discussion: Clinical and epidemiological information indicates high incidence rates, which have fluctuated in recent years, with significant co-circulation of several serotypes at the same time. Conclusions: Notorious surveillance data collection differences were identified between countries, determining a heterologous epidemiological pattern.

To TST or not to TST: is tuberculin skin testing necessary before BCG immunisation in children?

Bacille Calmette-Guérin (BCG) vaccine is one of the most commonly administered vaccines worldwide. In countries with high tuberculosis (TB) prevalence, it is generally given shortly after birth. In a number of low TB prevalence countries, BCG is used as a travel vaccine, typically given to children outside the neonatal period prior to visiting regions where TB is common. In this setting, it is recommended that latent TB infection (LTBI) resulting from prior exposure to Mycobacterium tuberculosis is excluded by a tuberculin skin test (TST) before BCG immunisation. This is to avoid the risk of an accelerated local reaction that is more common in individuals who have LTBI. In addition, BCG immunisation in individuals with LTBI is unnecessary, as it does not provide protection against progression to active TB disease. We review and discuss current international guidelines and recommendations on the need to screen children for LTBI prior to BCG immunisation. Guidelines vary significantly regarding age-related cut-offs and additional selection criteria. This variation primarily reflects the lack of evidence on which to base recommendations. We suggest an alternative strategy using a risk assessment questionnaire to identify children who should have a TST before BCG immunisation. This targeted approach will reduce the number of children unnecessarily screened, whilst allowing the identification of those with LTBI, who need further evaluation and treatment.

Enfermedad neumocóccica: nuevos retos y propuestas para América Latina / Pneumococcal disease: new challenges and new proposals for Latin America

La enfermedad neumocóccica invasora (ENI) es la primordial causa de muertes prevenibles mediante vacunación en niños bajo 5 años de edad en el mundo; en Latinoamérica y El Caribe representa una enorme carga de enfermedad. Con el fin de combatir la creciente incidencia de ENI en nuestra región, la gran mayoría de los países han incorporado las vacunas neumocóccicas como estrategia preventiva. El grupo GREEN (Grupo Regional de Estudio de la Enfermedad Neumocócica) ha sido creado para estudiar la enfermedad neumocóccica, unificar los datos generados por los países latinoamericanos y detallar la epidemiología pre y post-vacunación neumocóccica.

Invasive pneumococcal disease (IPD) is the leading cause of vaccine preventable deaths in children < 5 years worldwide and it causes a significant disease burden in Latin America and the Caribbean. In order to combat the increasing incidence of IPD in our region, the vast majority of countries have included pneumococcal vaccines as a preventive strategy. The GREEN group (Grupo Regional de Estudio de la Enfermedad Neumococica) has been created to study pneumococcal disease, unify data from the Latin American countries and learn in detail the epidemiology pre and post-pneumococcal vaccination.

48th ICAAC/46th IDSA Annual Meeting: a pediatric perspective.

A combined meeting of the American Society of Microbiology and the Infectious Diseases Society of America was held recently in Washington, DC, USA, which gathered worldwide experts in the fields of infectious diseases, microbiology and the pharmaceutical industry, among others. Owing to its huge attendance and being among the largest conferences in the world during the year for infectious disease specialists, we focus only in the most relevant issues related to pediatric vaccines. Among others, we mention dengue, rotavirus, HIV, influenza virus, Streptococcus pneumoniae, Neisseria meningitidis, pertussis, measles and mumps. The case with mumps and measles illustrates the negative impact that vaccine refusal, fears and low coverage rates have on the resurgence of outbreaks produced by these two viruses. However, even with full vaccination schedules, other factors, such as waning immunity, influence the resurgence of these old diseases: pertussis, measles and mumps. This illustrates the importance of continuous surveillance in the epidemiology of vaccine-preventable diseases once a vaccine is licensed and introduced in a given population.

Búsqueda retrospectiva del síndrome de rubéola congénita en niños menores de 1 año / Retrospective search for Congenital Rubella Syndrome in Children under one year

Antecedentes: Costa Rica estableció la meta de eliminación del síndrome de rubéola congénita desde el año 2000. Datos oficiales de vigilancia reportan el último caso autóctono confirmado en el 2001. Para evaluar si se logró la meta de eliminación de la enfermedad se analizó, mediante una búsqueda retrospectiva, la calidad de la vigilancia del síndrome para determinar la existencia de casos que no fueron capados por el sistema vigente...

Seroprevalence of dengue virus antibodies in asymptomatic Costa Rican children, 2002-2003: a pilot study.

OBJECTIVES: Since 1993 dengue has become more frequent in Costa Rica. Adults have been the most affected population, while children have remained virtually unharmed. So far no studies have investigated how many asymptomatic children have been affected by this virus. This pilot study documents the seroprevalence, measured as the presence of IgG antibodies, of dengue virus in asymptomatic children from two different geographical areas. METHODS: This descriptive, prospective epidemiologic study compared the presence of antibodies in children who live in a coastal region of a tropical country where dengue is endemic, and an inland area where dengue is not endemic. An enzyme-linked immunosorbent assay was used to test the serum for dengue virus IgG antibodies. None of the children had a prior history of dengue, fever, immunosuppressive therapy or underlying disease. RESULTS: During the period from July 2002 to July 2003, 103 children were recruited from each area. In the costal region we found a seroprevalence of 36.9%. In the inland area seroprevalence was 2.9%. CONCLUSIONS: We found a substantial number of asymptomatic infections in Costa Rican children. This greatly increases the risk of dengue hemorrhagic fever or dengue shock syndrome in these children, in whom previous dengue infection had gone undetected. Preventive efforts should be targeted at the costal region due to the higher prevalence in this area.