Risk Factors for Death and Severe Neurological Sequelae in Childhood Bacterial Meningitis.

INTRODUCTION: Acute bacterial meningitis (ABM) continues to be a challenge from a diagnostic and therapeutic point of view. Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcome. METHODS: Data from a retrospective study for ABM in children admitted to the Institute of Tropical Medicine in Paraguay was analyzed. ABM was defined as positive cerebrospinal fluid culture, positive latex agglutination, or identification of microorganism by real time-polymerase chain reaction. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed. A point-based scoring system that included variables, which were clearly different among those who passed away, was constructed. RESULTS: One hundred fourteen children hospitalized with ABM were eligible for the study. The mean age was 46 ± 57 months (range, 1-192 months). The observed mortality was 33% (38/114 patients). When a point-based scoring system was used, for score of 0 (n = 29) and 1 (n = 12), no death was observed. Among patients with a score of 2 (n = 14), 3 (n = 10 patients), 4 (n = 12 patients), and 5 (n = 13 patients), the mortality rate was 14.3%, 40%, 50%, and 53.8%, respectively. When the score was 6 or higher, the mortality rate was at least 63.6%. CONCLUSIONS: The present score accurately discriminated the probability of death in children hospitalized with ABM, and it could be a useful tool to select candidates for admission to the intensive care unit and for adjunctive therapy in clinical trials.

Public health and budget impacts of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Paraguay.

This study aimed to investigate the public health and economic benefit of using a quadrivalent influenza vaccine (QIV) instead of a trivalent influenza vaccine (TIV) in past seasons in Paraguay. The budget impact of switching from TIV to QIV in the Immunization Program was also evaluated. The adapted model includes two modules. The first compared retrospectively Health and Economic outcomes resulting from the use of QIV instead of TIV. The second forecast the spending and savings that would be associated with the switch from TIV to QIV. Our findings estimate that the switch from TIV to QIV during the seasons 2012 to 2017 could have prevented around 2,600 influenza cases, 67 hospitalizations and 10 deaths. An alternative scenario using standardized estimates of the burden of influenza showed that 234 influenza-related hospitalizations and 29 deaths could have been prevented. The estimated annual budget impact of a full switch from TIV to QIV was around USD1,6 million both from the payer and societal perspectives. Those results are mainly driven by vaccine prices and coverage rate. In sum, this manuscript describes how the use of QIV instead of TIV could have prevented influenza cases and subsequent complications that led to hospitalizations and deaths. This could have generated savings for the health system and society, offsetting part of the additional investment needed to switch from TIV to QIV.

[Dengue economic impact in Paraguay]. / Impacto económico del dengue en Paraguay.

BACKGROUND: Since the end of the 20th century, dengue has periodically devastated Paraguay. Its high morbidity and mortality translate into a high global socio-economic impact and a high burden on health care systems. AIM: To determine the economic cost and burden of dengue in Paraguay. METHODS: The direct and indirect costs of dengue were estimated in both outpatient and hospitalized cases. Likewise, the years of life adjusted for disability (DALY) were calculated from the sum of the years of life lost (YPLL) due to premature mortality in the population and years lost due to disability (DVSP). RESULTS: The unit cost per ambulatory case was US dollars 52.5 and for hospitalized patients US dollars 300 with a total cost for the 4 years of US dollars 276,804.864 and US dollars 23,236.45, respectively. The AVPP were 18,469.7 per million inhabitants; the DVSP of 185,835 and the DALYs 32,676 years per million inhabitants. CONCLUSIONS: Dengue imposes considerable costs for both the health sector and the economy in general in Paraguay.

Non-structural protein 1 (NS1) of dengue virus detection correlates with severity in primary but not in secondary dengue infection.

BACKGROUND: Non-structural protein 1 (NS1) of dengue virus circulates in the serum of patients during the acute phase of the disease. OBJECTIVES: To determine whether NS1 screening can serve in diagnosing primary and secondary infection and to evaluate its utility as a marker for predicting the severity of dengue in children. STUDY DESIGN: Patients ≤15 years of age hospitalized for dengue between 2012-2018, with NS1 determination (Panbio, Australia) were included. Clinical y laboratorial characteristics were collected in a standardized data table for analysis of correlation between serotypes, primary or secondary condition of infection, severity, and presence of NS1. RESULTS: Of 709 children hospitalized for dengue with NS1 determination, 479 (67.5 %) had the positive test. Of the 378 primary cases, 320 (85 %) were NS1 (+). while among the 242 secondary cases only 103 (42.5 %) were NS1 (+) (p < 0001). Of the 479 patients with NS1 (+), 344 (72 %) were warnig-signed cases (WSC) and 94 (19 %) were severe cases (SC), being these figures 62 % and 34 %, in the NS1 negative patients respectively (p < 0.001). There was no difference in the frequency of WSC or SC between patients with NS1 positive or negative test in secondary dengue; however, in primary dengue, the figures were 68 % vs 32 % (p < 0.001), and 87 % vs 12 % (p < 0.001), respectively. CONCLUSIONS: The presence of NS1 positive test is associated with the condition of infection (primary or secondary) and exhibited an increased risk of developing forms with warning signs or severe dengue in primary cases, but not in secondary cases.

Mortality Predictive Scores for Community-Acquired Pneumonia in Children.

PURPOSE OF REVIEW: The use of severity score for the staging of pneumonias has emerged as a necessity for the physician caring for this disease. Although there are several established prognostic scoring systems for community-acquired pneumonia in adults, the availability for children are scarce. RECENT FINDINGS: Recently, scoring system for risk stratification of children with pneumonia were developed in low- and middle-income countries. They use clinical variables that represent known risk factors for severe outcomes of respiratory illness in children, such as hypoxemia, chest indrawing, refusal to feed, malnutrition, age, and stage of HIV disease among others factors. Although they showed good discriminating power and are very useful in low-resource settings, the characteristics of the patients, the local epidemiology of concurrent diseases, the social conditions, and the facilities of the hospitals make them not applicable to developed countries. A new prognostic scale for estimating mortality based on the modified PIRO scale used in adults with pneumonia can be useful for developed countries. Although several scoring systems for the estimation of mortality in childhood CAP were developed in the last years, most of them come from developing countries and the results are not applicable to patients with pneumonia in developed countries. Prospective studies applying scores adapted to the reality of the developed countries are needed.

Prognostic factors of severity of invasive community acquired Staphylococcus aureus infections in children. / Factores pronósticos de gravedad de las infecciones invasivas por Staphylococcus aureus adquiridas en la comunidad en niños.

OBJECTIVE: To describe the clinical characteristics of invasive Staphylococcus aureus infections in children and identify the prognostic factors of severity and mortality. MATERIALS AND METHODS: Observational study in patients < 16 years old hospitalized between 2010 and 2015 due to invasive S. aureus infections at the Instituto de Medicina Tropical, in Asunción, Paraguay. Patients were distributed based on whether or not they required admission to the intensive care unit, and clinical, laboratory, and evolutionary outcome measures were compared. RESULTS: Out of the 107 included patients, 50 (47 %) developed bacteremia; 50 (47 %), pneumonia; and 21 (19 %), multifocal disease. Among the patients who were admitted to the intensive care unit (41 %), prior antibiotic use (p < 0.05), the presence of bacteremia (p = 0.01), the presence of comorbidities (p < 0.05), and multifocal disease (p < 0.01) were more frequent. The overall mortality rate was 15 %. The mortality-associated risk factors were the presence, at the time of admission, of hypotension (p < 0.01), multifocal disease (p < 0.01), bacteremia (p < 0.01), leukopenia (p < 0.01), severe anemia (p < 0.01), and metabolic acidosis (p < 0.01), among others. CONCLUSIONS: The prognostic factors of severity included prior antibiotic use, bacteremia, the presence of comorbidities, and presentation with multifocal disease. Mortality was significant; associated risk factors included the presence, at the time of admission, of hypotension, multifocal disease, leukopenia, severe anemia, and metabolic acidosis.

Objetivo: Describir las características clínicas de las infecciones invasivas por Staphylococcus aureus en niños e identificar los factores pronósticos de gravedad y mortalidad. Materiales y métodos: Estudio observacional, en pacientes < 16 años hospitalizados en 2010- 2015 por infecciones invasivas por S. aureus en el Instituto de Medicina Tropical, de Asunción, Paraguay. Los pacientes se distribuyeron según si habían requerido ingresar a la Unidad de Cuidados Intensivos o no, y se compararon variables clínicas, de laboratorio y evolutivas. Resultados: De los 107 pacientes incluidos, 50 (el 47 %) presentaron bacteremia; 50 (el 47 %), neumonía; y 21 (el 19 %), sepsis con focos múltiples. En los pacientes que ingresaron en la Unidad de Cuidados Intensivos (el 41 %), el uso previo de antibiótico (p < 0,05), la presencia de bacteremia (p = 0,01), de comorbilidad (p < 0,05) y la presentación con focos sépticos múltiples (p < 0,01) fueron más frecuentes. La mortalidad global fue del 15 %. Factores de riesgo asociados a mortalidad fueron, entre otros, la presencia, de hipotensión al ingresar (p < 0,01), focos sépticos múltiples (p < 0,01), bacteremia (p < 0,01), leucopenia (p < 0,01), anemia grave (p < 0,01) y acidosis metabólica (p < 0,01). Conclusiones: Los factores pronósticos de gravedad fueron el uso previo de antibióticos, la bacteremia, la presencia de comorbilidad y la presentación con focos sépticos múltiples. La mortalidad fue significativa; los factores de riesgo asociados fueron la presencia, al ingresar, de hipotensión, focos sépticos múltiples, leucopenia, anemia grave y acidosis metabólica.

Factors associated with vancomycin-resistant enterococci colonization in a pediatric intensive care unit of Paraguay: A cross-sectional study on hospital charts. / Factores asociados a colonización por enterococo sp resistente a vancomicina en una unidad de cuidados intensivos pediátricos del Paraguay: estudio transversal sobre historias clínicas.

INTRODUCTION: Vancomycin-resistant enterococci (VRE) infections have become widespread and a challenge in hospitalized patients. The threat of infection by intractable enterococci and the possibility that vancomycin resistance could involve pneumococci or staphylococci advocate for careful surveillance of resistant strains. OBJECTIVE: To determine the risk factors associated with VRE colonization in pediatric patients admitted to the Pediatric Intensive Care Unit (PICU) in the period between January 2012 and June 2013. METHODS: We conducted a cross-sectional study analyzing the clinical histories of 140 patients admitted to the PICU (children from 1 month to 18 years) who underwent rectal swab cultures within 48 hours of admission. We calculated the odds ratios and confidence intervals of the risk factors for VRE colonization in the PICU, and then we used multiple logistic regression for the statistically significant variables. RESULTS: VRE colonization was present in 18.6% of patients. The following variables were identified as risk factors associated with VRE colonization: prior hospitalization in the past year (odds ratio: 10.8; 95% confidence interval: 2.43 to 47.8; p = 0.001); prior use of one broad-spectrum antibiotic (odds ratio: 5.05; 95% confidence interval: 2.04 to 12.5; p = 0.000); use of two or more broad-spectrum antibiotics in past year (odds ratio: 5.4; 95% confidence interval: 1.5 to 18.4; p = 0.009); prior hospitalization in a high-risk area (odds ratio: 4.91; 95% confidence interval: 1.83 to 13.2; p = 0.000); hospitalization for more than five days in a high-risk area (odds ratio: 5.64; 95% confidence interval: 2.18 to 14.6; p = 0.000); and use of immunosuppressant drugs (odds ratio: 4.84; 95% confidence interval: 1.92 to 11.9; p = 0.001). In a logistic multiple regression the use of two or more broad-spectrum antibiotics (odds ratio: 4.81; 95% confidence interval: 1.01 to 22.8; p = 0.047) and prior hospitalization in past year (odds ratio: 7.84; 95% confidence interval: 1.24 to 49.32; p = 0.028) were identified as independent factors statistically associated with VRE colonization. CONCLUSION: Pediatric patients admitted for intensive care with a history of prior hospitalization in the past year and exposure to two or more broad-spectrum antibiotics have a greater risk of colonization by vancomycin-resistant enterococci.

INTRODUCCIÓN: Las infecciones por Enterococcus sp resistente a la vancomicina se han diseminado y generan un desafío clínico-terapéutico en los pacientes hospitalizados. La amenaza de que la infección por enterococos intratables y la posibilidad que la resistencia a la vancomicina pueda propagarse a neumococos o estafilococos, abogan por la vigilancia atenta de las cepas resistentes. OBJETIVO: Determinar los factores de riesgos asociados a la portación de Enterococcus sp resistente a la vancomicina en pacientes pediátricos ingresados en una unidad de cuidados intensivos pediátricos del Paraguay en el periodo entre enero de 2012 y junio de 2013. MÉTODOS: Estudio transversal. Se analizaron las historias clínicas previas de 140 pacientes ingresados a terapia intensiva (niños de un mes a 18 años), a quienes se realizaron cultivos de hisopado rectal dentro de las 48 horas del ingreso, para determinar los factores asociados a la portación de Enterococcus sp resistente a la vancomicina en unidad de cuidados intensivos pediátricos. Se calculó el Odd ratio con sus intervalos de confianza y p < 0,05 para las variables de estudio. Posteriormente, se realizó regresión logística múltiple para las variables estadísticamente significativas. RESULTADOS: La portación de Enterococcus sp resistente a la vancomicina se observó en 18,6% de los pacientes. Se identificaron como factores asociados: la hospitalización previa durante el último año (Odds ratio: 10,8; intervalo de confianza 95%: 2,43 a 47,8; p = 0,001), uso previo de antibióticos de amplio espectro (Odds ratio: 5,05; intervalo de confianza 95%: 2,04 a 12,5; p = 0,000), uso de dos o más antibióticos de amplio espectro en el último año (Odds ratio: 5,4; intervalo de confianza 95%: 1,5 a 18,4; p = 0,009), internación previa en área de alto riesgo (Odds ratio: 4,91; intervalo de confianza 95%: 1,83 a 13,2; p = 0,000), internación por igual o mayor a seis días en área de alto riesgo (Odds ratio: 5,64; intervalo de confianza 95%: 2,18 a 14,6; p = 0,000) y uso de inmunosupresores (Odds ratio: 4,84; intervalo de confianza 95%: 1,92 a 11,9; p = 0,001). La regresión múltiple señala a la utilización de dos o más antibióticos de amplio espectro (Odds ratio: 4,81; intervalo de confianza 95%: 1,01 a 22,8; p = 0,047) y a la historia de hospitalización previa dentro del año (Odds ratio: 7,84; intervalo de confianza 95%: 1,24 a 49,32; p = 0,028) como factores independientes asociados estadísticamente con la portación de Enterococcus sp resistente a la vancomicina. CONCLUSIÓN: Los pacientes pediátricos ingresados en la unidad de cuidados intensivos con historia de internación previa dentro del año y la exposición a dos o más antibióticos de amplio espectro, tienen mayor riesgo de colonización por el enterococo resistente a vancomicina.

Clinical manifestations of primary and secondary dengue in Paraguay and its relation to virus serotype.

INTRODUCTION: Dengue virus (DENV) infection is currently a major cause of morbidity in the world, and its incidence has mainly increased during the last years in Latin America, including Paraguay. The objective of this study was to compare the clinical and laboratory findings of dengue and assess whether the serotype is a risk factor for severity. METHODOLOGY: We included patients ≤ 15 years old hospitalized with dengue at the Institute of Tropical Medicine, from Paraguay, from 2007 to 2018. Patients were classified according to the 2009 WHO dengue classification guidelines and were stratified by serotype into three groups according to the hospitalization period: the 2007 epidemic (DENV-3), the 2012-2013 epidemic (DENV-2) and the 2016-2018 epidemic (DENV-1). RESULTS: Of 784 children hospitalized for dengue, 50 cases (6.3%) were caused by DENV-3, 471 (60%) by DENV-2, and 263 (33.5%) by DENV-1. Myalgias and headache were associated with DENV-3 cases and abdominal pain was associated with DENV-2 cases. Bleeding was observed mainly in DENV-1 and 2 cases. Patients with DENV-2 infections experienced more severe disease, required fluid expansion more frequently, and exhibited more often shock and admission in the ICU. Secondary cases of dengue were more severe that primary cases. Patients with infection by DENV-2 had longer hospital stays (5.1 ± 2.8 days) when compared to DENV-3 o DENV-1 infection cases (2.9 ± 1.6 days and 4.36 ± 2.7 days, respectively) (p < 0.05). CONCLUSIONS: The DENV serotype has a profound impact on the clinical manifestations and severity of dengue. DENV-2 infections were associated more frequently to requirement of fluid expansion, shock, and longer hospital stay.

Remarks on the possibility of introducing the fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule.

Given that the last notified case of poliomyelitis due to wild poliovirus type 2 was in 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of a bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported a reduction of the global supply of IPV. In response to the potential shortage of IPV, at a meeting held on March 10 2017, the SAGE and Technical Advisory Group (TAG) of the Pan American Health Organization (PAHO) urged the countries in the Latin American region to replace the routine administration of the full doses of inactivated polio vaccine (IPV-C) in the immunization schedule (administered by intramuscular route), administering a fraction of the full dose in two intradermal shots (IPV-f). The possibility of this strategy was analyzed by opinion leaders convened by the Paraguayan Society of Pediatrics with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). This document presents the results of the discussion.

Influence of admission findings on death and neurological outcome from childhood bacterial meningitis.

A post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousness is the most important predictor of death and/or neurological sequelae, more than is etiology per se. This finding emphasizes the need of including a measurement of the presenting status in all studies examining treatment efficacy.

[Remarks on the possibility of the introduction of fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule]. / Consideraciones referente a la posibilidad de introducir la dosis fraccionada de la vacuna antipoliomielitis inactivada en el calendario de Inmunizaciones del Niño Latinoamericano.

As last notified case of poliomyelitis due to wild poliovirus type 2 was 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported reduction in IPV global supply. In response to the possible shortage of IPV, the SAGE and Technical Adviser Group (TAG) of the Pan American Health Organization (PAHO), in the meeting of March 10, 2017, has urged that countries in the Latinamerican region should replace the routine administration of the full doses of polio inactivated vaccine (IPV-C) in the immunization schedule (administered by intramuscular route) by the administration of a fraction of the full dose in two shots by intradermal route (IPV-f). The possibility of this strategy was analyzed by leaders of opinions gathered by the call of the Paraguayan Pediatric Society with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). The results of the discussion are presented in this document.

Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually. METHODS: We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models. RESULTS: H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014). CONCLUSION: Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.

Influencia del Cambio Climático en las Enfermedades Transmitidas por Vectores

Los cambios ecológicos influyen fuertemente en los patrones de enfermedad. En la presente centuria, la inestabilidad climática y el calentamiento progresivo están desempeñando un papel creciente en la emergencia de nuevas enfermedades infecciosas, así como en la reaparición y redistribución de olvidadas infecciones. El objetivo del presente trabajo es analizar y contrastar la interrelación del clima, lluvias y temperatura, con las epidemias de dengue, arbovirosis que se ha convertido en un azote terrible en nuestro país. Metodología: Estudio descriptivo, observacional, done el número de casos de dengue durante los años 2012, 2013 y 2014, fueron contrarrestados con el promedio mensual de lluvia caída y la temperatura media mensual en el mismo periodo de tiempo. Tanto los datos de número de casos de dengue por mes, así como los datos promedios de lluvia y temperatura en cada mes se correlacionaron, estimándose la significancia estadística mediante el cálculo del coeficiente de correlación de Pearson. Resultados: Durante los 3 años del estudio, se constató un patrón característico de ocurrencia presentándose c el incremento de casos de dengue entre los meses de diciembre y mayo con un pico máximo entre febrero y abril. La media de lluvia caída predominó globalmente en el primer semestre de cada año, aunque presentó algunas diferencias anuales. El incremento del número de casos de dengue fue claramente influenciado por variaciones climáticas tanto de temperatura, con un incremento de los casos de dengue con temperaturas entre 20 y 25ºC y de lluvia caída. Al analizar en forma separada la influencia de ambas variables climáticas, pudo observarse que el principal factor que se correlacionó con los casos de dengue fue la magnitud de las precipitaciones (r de Pearson de 0.6214), y en menor grado la temperatura (r de Pearson 0,4082). Conclusión: Se observa una correlación de los casos de dengue en el Paraguay con variables climáticas, principalmente el ritmo de las precipitaciones, muestra el gran impacto del clima en la ocurrencia de epidemias de dengue.

Ecological changes strongly influence disease patterns. In this century, climatic instability and progressive warming are playing an increasing role in the emergence of new infectious diseases, as well as in the reappearance and redistribution of neglected infections. The objective was to analyze and contrast the interrelation of climate, rainfall and temperature, with dengue epidemics, an arbovirosis that has become a terrible scourge in our country. Methodology: Descriptive, observational study, where the number of dengue cases during the years 2012, 2013 and 2014, were counteracted with the monthly average rainfall and the average monthly temperature in the same period of time. Both the data on the number of dengue cases per month, as well as the average data on rainfall and temperature in each month were correlated, estimating the statistical significance by calculating the Pearson correlation coefficient. Results: During the 3 years of the study, a characteristic pattern of occurrence was found, presenting an increase in dengue cases between the months of December and May with a maximum peak between February and April. The mean rainfall predominated globally in the first semester of each year, although it presented some annual differences. The increase in the number of dengue cases was clearly influenced by climatic variations in both temperature, with an increase in dengue cases with temperatures between 20 and 25ºC and rain fall. When analyzing the influence of both climatic variables separately, it was possible to observe that the main factor that was correlated with dengue cases was the amount of rainfall (Pearson's r of 0.6214), and to a lesser extent temperature (Pearson's r of 0.6214). 0.4082). Conclusion: A correlation of dengue cases in Paraguay with climatic variables is observed, mainly the rate of rainfall, showing the great impact of climate on the occurrence of dengue epidemics.

Estudio aleatorizado, doble ciego, placebo controlado de doxiciclina en pacientes con dengue. Modulación de citoquinas y respuesta clínica

Resumen Introducción: Los niveles de citoquinas podrían ser determinantes en la severidad de la Fiebre Dengue. La supresión de su actividad con inmunomoduladores modificaría su evolución. Objetivo: Determinar el efecto de la adición de doxiciclina sobre el perfil de citocinas de pacientes con dengue y valorar la respuesta clínica y el impacto en la severidad de pacientes con Fiebre de Dengue. Materiales y métodos: Estudio aleatorio, doble ciego, placebo controlado con doxiciclina. Ambos grupos recibieron la medicación por 7 días y se controló la evolución clínica, laboratorio y niveles de citoquinas en los días 0, 3 y 7. Resultados: Fueron incluídos en el estudio 61 pacientes, 36 (59%) en el grupo placebo y 25 (41%) en el grupo doxiciclina. Se observó que los pacientes tratados con doxiciclina mostraron menor plaquetopenia en el día 0 y 3 [(170029±47483/mm3 vs 198875±52211/mm3)(p<0,05) y 129545±62840/mm3 vs 165048±51142/mm3)(p<0,05)] al compararlo con el grupo placebo. Los niveles de IL-6, TNF y raIL-1 no mostraron diferencias significativas. Se observó una tendencia a menores niveles de IL-1ß en el grupo tratado con doxiciclina (52,1±97 vs 3,3±7,7)(0,08). Conclusiones: No se constató diferencias en la presentación clínica, hospitalización ni en la mortalidad entre pacientes tratados con doxiciclina comparados con placebo. Hubo una tendencia a menores niveles de IL-1ß en los pacientes tratados con doxiciclina. Debe aumentarse el tamaño de la muestra para confirmar o rechazar los resultados.

Abstract Background: Cytokine levels could be determinant in the severity of Dengue Fever. The suppression of their activity with immunomodulators would modify its evolution. Objective: To determine the effect of doxycycline on the cytokine profile of patients with dengue fever and to assess the clinical response and the impact on the severity of patients with dengue fever. Materials and methods: Randomized, double-blind, placebo-controlled study with doxycycline. Both groups received the medication for 7 days and clinical evolution, laboratory and cytokine levels were monitored on days 0, 3 and 7. Results: 61 patients were included in the study, 36 (59%) in the placebo group and 25 (41%) in the doxycycline group. It was observed that patients treated with doxycycline showed lower thrombocytopenia at day 0 and 3 [(170029±47483/mm3 vs 198875±52211/mm3)(p<0.05) and 129545±62840/mm3 vs 165048±51142/mm3)(p<0.05)] when compared to the placebo group. IL-6, TNF and raIL-1 levels showed no significant differences. A trend to lower IL-1ß levels was observed in the doxycycline treated group (52.1±97 vs 3.3±7.7)(0.08). Conclusions: There was no difference in clinical presentation, hospitalization or mortality among patients treated with doxycycline compared to placebo. There was a trend to lower IL-1ß levels in patients treated with doxycycline. The sample size should be increased to confirm or reject the results.

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.

Opsonic requirements for the respiratory burst of neutrophils against Giardia lamblia trophozoites.

BACKGROUND: Giardia lamblia is an important cause of parasitic diarrheal disease worldwide. Occasionally, polymorphonuclear neutrophils (PMNs) may participate as effector cells against Giardia lamblia. The present study was performed in order to examine the role of specific antibody and complement components in promoting the respiratory burst (RB) of PMNs against Giardia lamblia. METHODS: PMNs from human adult volunteers were incubated with Giardia trophozoites in the presence of non-immune (NS) or hyperimmune (HS) serum (anti-Giardia titer, >1:1024). Adherence was scored visually on coverslide after staining with Giemsa. The ability of Giardia to trigger the oxidative response of PMNs was measured by the anion superoxide (O2(-)) production using a cytochrome C reduction method and by the luminol amplified chemiluminescence (CL) assay. RESULTS: Incubation with NS or HS increased Giardia adherence to PMNs from 6.9 +/- 3.2% (basal adherence of Giardia incubated in buffer) to 39 +/- 18.6% (p <0.01) and 76 +/- 19.5% (p <0.001), respectively. In absence of serum, Giardia failed to trigger an oxidative response of PMNs. Opsonization with NS or HS increased the PMN O2(-) production from 3.9 +/- 0.92 nmol/2.5 x 10(6) PMNs/10 min to 9.04 +/- 1.68 (p <0.05) and 17.9 +/- 1.32 (p <0.001), respectively. A similar enhancement of the CL response was also observed. The inactivation of complement activity by heat as well as the elimination of specific antibodies by absorption produced a significant abrogation of the oxidative response but in the case of HS heat inactivation alone did not abolish the response. Similar findings (variable abrogation of the oxidative PMN response) were observed when PMNs were incubated with monoclonal antibodies directed against complement C3, C3b or the low-affinity Fc receptors (CR1, CR3 or FcRlo). CONCLUSIONS: These results show that complement components and specific antibodies influence in the Giardia-PMN interaction. Although components of complement can contribute to the RB of PMNs, specific antibodies are critical for an optimal oxidative PMN response.

Application of a Prognostic Scale to Estimate the Mortality of Children Hospitalized with Community-acquired Pneumonia.

BACKGROUND: Pneumonia is a major cause of mortality in children. The objective of this study was to construct a prognostic scale for estimation of mortality applicable to children with community-acquired pneumonia (CAP). METHODS: This observational study included patients younger than 15 years with a diagnosis of CAP who were hospitalized between 2004 and 2013. A point-based scoring system based on the modification of the PIRO scale used in adults with pneumonia was applied to each child hospitalized with CAP. It included the following variables: predisposition (age <6 months, comorbidity), insult [hypoxia (O2 saturation < 90), hypotension (according to age) and bacteremia], response (multilobar or complicated pneumonia) and organ dysfunction (kidney failure, liver failure and acute respiratory distress syndrome). One point was given for each feature that was present (range, 0-10 points). The association between the modified PIRO score and mortality was assessed by stratifying patients into 4 levels of risk: low (0-2 points), moderate (3-4 points), high (5-6 points) and very high risk (7-10 points). RESULTS: Eight hundred sixty children hospitalized with CAP were eligible for study. The mean age was 2.8 ± 3.2 years. The observed mortality was 6.5% (56/860). Mortality ranged from 0% for a low PIRO score (0/708 pts), 18% (20/112 pts) for a moderate score, 83% (25/30 pts) for a high score and 100% (10/10 pts) for a very high modified PIRO score (P < 0.001). CONCLUSION: The present score accurately discriminated the probability of death in children hospitalized with CAP, and it could be a useful tool to select candidates for admission to intensive care unit and for adjunctive therapy in clinical trials.

Estudio comparativo de la reacción de Mantoux con la determinación del Interferon Gamma en pacientes VIH-SIDA para el diagnóstico de la Tuberculosis latente (TBL)

Resumen La OMS estima que un tercio de la población mundial está infectada con Mycobacterium tuberculsosis, permaneciendo la mayoría de los casos en forma de TB latente (TBL). No existe un estándar de oro para el diagnóstico de la TBL, por lo cual la carga global de la misma. Objetivo: Comparar la efectividad en pacientes con VIH/SIDA de dos pruebas diagnósticas de TB latente (TBL): la Prueba de Mantoux y la determinación de Interferón Gamma en sangre periférica. Materiales y métodos: Estudio observacional, descriptivo y prospectivo con componente analítico, en el que se incluyeron consecutivamente por muestreo no probabilístico los pacientes de 18 meses a 60 años pacientes de ambos sexos, que acuden al consultorio del Programa Nacional de Control del VIH/sida con diagnóstico reciente de VIH/sida y en quienes se descartó TB activa. En todos los pacientes incluidos se realizó al mismo tiempo determinación del PPD (por inyección de tuberculina I de 2UI de potencia por inyección intradérmica en antebrazo izquierdo) y se tomó sangre periférica para determinación por el método de ELISA de la producción por los mononucleares de interferón gama en respuesta a antígeno de MTB (ELISA- QIAGEN - Germany). Resultados: Desde octubre 2017 a octubre de 2019, se identificaron 659 pacientes VIH que reunían los criterios de inclusión, de los cuales se incluyeron el 99, 9% (599 pacientes), quienes acudieron a la lectura de la prueba de la PPD. La edad media de los pacientes es de 34,1 años (DE 13,1 años), 415 (69%) son del sexo masculino. El 67,9% (407/599) procede del Dpto. Central y Asunción A todos los pacientes incluidos se les realizó la PPD y el test IGRA. La TBL se detectó en el 7,6% (46/599) pacientes, de los cuales, en 8,7% (52/599) el Gama Interferon fue positivo (IGRA) y en 3,8% (23/599) la PPD fue ≥5 (positivo). El 2% (12/599) pacientes fueron positivos para ambas pruebas. Al comparar los datos mencionados podemos observar que el IGRA resultó ser el método más efectivo para detectar la TBL, ya que con el mismo se identificó a 8,7% de los casos a diferencia de la PPD que solo permitió identificar el 2% de los mismos. El 100% (46/46) de los pacientes con diagnóstico con TBL recibieron quimioprofilaxis con Isoniacida. Conclusión: El presente estudio pretende definir el rendimiento de una nueva metodología para la detección de TB latente en una población de alto riesgo de coinfección como son los infectados con VIH.

Abstract The WHO estimates that one third of the world's population is infected with Mycobacterium tuberculosis, with the majority of cases remaining in the form of latent TB (TBL). There is no gold standard for the diagnosis of TBL, hence the global burden of it. Objective: To compare the effectiveness in patients with HIV / AIDS of two diagnostic tests for latent TB (TBL): the Mantoux Test and the determination of Interferon Gamma in peripheral blood. Materials and methods: An observational, descriptive and prospective study with an analytical component, in which patients between 18 months and 60 years of age, patients of both sexes, were consecutively included by non-probabilistic sampling, who attended the office of the National HIV / AIDS Control Program with a recent diagnosis of HIV / AIDS and in whom active TB was ruled out. In all the patients included, PPD was determined at the same time (by injection of tuberculin I of 2IU of potency by intradermal injection in the left forearm) and peripheral blood was taken for determination by the ELISA method of the production of interferon mononuclear cells. gamma in response to MTB antigen (ELISA- QIAGEN - Germany). Results: From October 2017 to October 2019, 659 HIV patients meeting the inclusion criteria were identified, of which 99.9% (599 patients) were included, who attended the reading of the PPD test. The mean age of the patients is 34.1 years (SD 13.1 years), 415 (69%) are male. 67.9% (407/599) came from the Central and Asunción Departments. All patients included underwent the PPD and the IGRA test. TBL was detected in 7.6% (46/599) patients, of which, in 8.7% (52/599) the Interferon range was positive (IGRA) and in 3.8% (23/599) PPD was ≥5 (positive). 2% (12/599) patients were positive for both tests. When comparing the aforementioned data, we can see that the IGRA turned out to be the most effective method for detecting TBL, since with it 8.7% of the cases were identified, as opposed to the PPD, which only allowed the identification of 2% of the cases. themselves. 100% (46/46) of the patients diagnosed with TBL received chemoprophylaxis with Isoniazid. Conclusion: The present study aims to define the performance of a new methodology for the detection of latent TB in a population at high risk of coinfection such as those infected with HIV.

Clinical Characteristics and Risk Factors of Dengue Shock Syndrome in Children.

BACKGROUND: Dengue shock syndrome (DSS) represents one of the most severe manifestations of dengue virus infection. The objective of the present study was to analyze the clinical and laboratory characteristics, risk factors and outcome of DSS in children. METHODS: Patients <15 years old admitted with DSS during the 2012 and 2013 outbreak of serotype 2 of dengue virus in Paraguay were included. Demographic, clinical and laboratory data of patients with/without DSS were analyzed. RESULTS: Of 471 children hospitalized with dengue, 354 patients (75%) presented with shock at admission or developed later. The mean age of patients with DSS was 10.2 ± 4 years (no difference with patients without shock), without gender preference. Rash (50% vs. 56%), myalgias (45% vs. 40%), vomiting (66% vs. 68%) and bleeding manifestations (24% vs. 21.2%) were similar for 2 groups. Similarly, there was no difference in the frequency of DSS between primary versus secondary infection cases (76.2% vs. 71.6%, P = 0.3). Age group >5 years [odds ratio (OR) 1.6, 95% confidence interval (CI): 1-2.8, P < 0.05), presence of abdominal pain (OR 2.5, 95% CI: 1.3-4.9, P = 0.006), an activated partial thromboplastin time prolonged (OR 4; 95% CI: 1.6-10, P < 0.001) and low fibrinogen level (OR 2.5; 95% CI: 1-5.9, P = 0.02) were found significantly associated with DSS. About 12% of patients required intensive care unit admission, and 2 patients died (lethality 0.35%). CONCLUSIONS: This study validated most of the clinical variables present in the current WHO guidelines as markers of severe disease and add additional variables that can help to predict the risk of progression to shock.

Factores de riesgo potenciales en infecciones sistémicas por Candida sp

Resumen Objetivo: Determinar los factores de riesgo de infección diseminada en niños hospitalizados con candidemia. Materiales y métodos: Se realizó un estudio en una cohorte de niños hospitalizados con candidiasis sistémica. La cohorte fue definida por todos los pacientes con hemocultivos positivos para las especies de Candida sp. en el Instituto de Medicina Tropical. Los casos fueron pacientes con evidencia clínica, microbiológica o radiográfica de candidiasis sistémica. Los controles fueron pacientes sin evidencia de candidiasis sistémica. Resultados: En el total de 25 niños con candiermia, la edad media fue de 4,7 años. El 52% fue Candida albicans, la incidencia aumentó en los últimos 5 años, los menores de 1 año son los más afectados. Además del hemocultivo, el sitio predominante de aislamiento fue el catéter (72%), la fiebre, hipotensión y deterioro del sensorio son los hallazgos clínicos predominantes. El 56% de los pacientes fueron tratados con fluconazol (14/25) y el resto de los pacientes tratados con Anfotericina B. Los factores de riesgo encontrados fueron la presencia de catéter y estancia prolongada en UTI (56% y 36% respectivamente) Conclusiones: El uso de catéter y estancia prolongada en UTI mas de tres días fueron factores de riesgo para la candidiasis diseminada en niños con candidemia.

ABSTRACT Objective: To determine the risk factors of disseminated infection in hospitalized children with candidemia. Materials and methods: A study was conducted in a cohort of children hospitalized with systemic candidiasis. The cohort was defined by all the patients with positive blood cultures for the species of Candida sp. at the Institute of Tropical Medicine. The cases were patients with clinical, microbiological or radiographic evidence of systemic candidiasis. Controls were patients with no evidence of systemic candidiasis. Results: In the total of 25 children with candiermia, the mean age was 4.7 years. 52% was Candida albicans, the incidence increased in the last 5 years, children under 1 year are the most affected. In addition to blood culture, the predominant site of isolation was the catheter (72%), fever, hypotension, and sensory impairment are the predominant clinical findings. 56% of the patients were treated with fluconazole (14/25) and the rest of the patients treated with Amphotericin B. The risk factors found were the presence of a catheter and a prolonged stay in the ICU (56% and 36% respectively). Conclusions: The use of catheter and prolonged stay in ICU more than three days were risk factors for disseminated candidiasis in children with candidemia.