Primer Consenso Nacional Intersociedades de Inmunización del Adulto. 2023

Las vacunas previenen millones de muertes cada año y su eficacia y seguridad han sido ampliamente establecidas. En términos económicos, la vacunación es una de las intervenciones sanitarias más costo efectivas, generando un importante ahorro y crecimiento económico que supone a largo plazo. Se ha demostrado que la vacunación de adultos disminuye la morbilidad y la mortalidad asociadas a enfermedades infecciosas prevenibles, reduciendo las complicaciones y las hospitalizaciones, incluidos los ingresos a las unidades de cuidados intensivos. Hemos elaborado este documento de consenso con el objeto de diseñar un esquema de vacunación pragmático, accesible y estandarizado del adulto, según categoría de riesgo y edad, sobre la base de la evidencia disponible de vacunas accesibles y nuevas vacunas habiendo utilizado el Tercer Consenso de la Sociedad Paraguaya de Infectología del 2019 como base para las recomendaciones finales.

SUMMARY Vaccines prevent millions of deaths each year, and their efficacy and safety have been widely established. In economic terms, vaccination is one of the most cost-effective health interventions, generating significant savings and long-term economic growth. Adult vaccination has been shown to decrease morbidity and mortality associated with preventable Infectious diseases, reducing complications and hospitalizations, including admissions to intensive care units. We have prepared this consensus document in order to design a pragmatic, accessible and standardized vaccination scheme for adults, according to risk category and age, based on the available evidence of available vaccines and new vaccines, having used the third consensus of the Paraguayan Infectious Diseases Society of 2019 as a basis for the final recommendations.

Genetic analysis of the ZNF804A gene in Mexican patients with schizophrenia, schizoaffective disorder and bipolar disorder.

BACKGROUND: Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group. METHODS: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene. RESULTS: Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p > 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls. CONCLUSIONS: Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.

Ten-year course of treated bipolar I disorder: The role of polarity at onset.

INTRODUCTION: Early-stage predictors of illness course are needed in bipolar disorder (BD). Differences among patients with a first depressive versus maniac/hypomanic episode have been stated, although in most studies, memory bias and time from onset to start of specialized treatment might interfere. The aim was to compare the first 10 years of illness course according to polarity at onset. METHODS: 49 type I BD patients admitted for treatment for a first-time affective episode and a following 10-year attendance to the institution were included. A retrospective year by year comparison according to polarity at onset (depressive (DPO) or maniac (MPO)) was performed. Cramer's V and Cohen d were computed to determine effect size. RESULTS: 59.2% (n = 29) started with MPO. Both groups were similar in demographic and social outcome characteristics, clinical features, and treatment variables. Patients with DPO reported more depressive episodes than MPO patients (U = 149.0 p < .001, Cohen's d = 0.87); both groups had a similar number of manic episodes. Only during the first year of follow-up, suicide attempts (SA) were more frequent in patients with DPO while the presence of a psychotic episode and psychiatric hospitalizations were more frequent in the MPO group. CONCLUSION: According to these findings, it can be concluded that illness onset is only indicative of depressive predominant polarity but is not related to other poor prognostic variables after the first year of illness onset, in treated BD. SA in the first year of an affective disorder could represent a marker of BD.

Brain perfusion during manic episode and at 6-month follow-up period in bipolar disorder patients: Correlation with cognitive functions.

BACKGROUND: Patterns of altered cerebral perfusion and cognitive dysfunction have been described in Bipolar Disorder (BD) acute episodes and euthymia. Knowledge of the relationship between cognitive function and perfusion in a manic state and status when followed up is still limited. OBJECTIVE: To describe brain perfusion alterations and its relationship with cognitive impairment in patients with BD during manic episodes and after 6 months. METHODS: Observational-prospective study in 10 type I BD adults during moderate-severe manic episodes. We assessed sociodemographic data and clinical variables as well as cognitive function through Screening for Cognitive Impairment in Psychiatry (SCIP-S). Finally, we performed a Brain Perfusion SPECT using a Tc99m-ethyl cysteine dimer. RESULTS: During manic episodes, patients showed cognitive impairment with a mean SCIP-S score of 63.8 ± 17.16. This was positively correlated with perfusion measured as relative reuptake index (RRI) at the right temporal pole (ρ = 0.65 p = .0435) and negatively correlated with right the orbitofrontal cortex (ρ = -0.70 p = .0077) and the right subgenual cingulate cortex (ρ = -0.70 p = .0256). Episode severity measured by the Young Mania Rating Scale (YMRS) positively correlated with RRI at the right temporal pole (ρ = 0.75, p = .01). At follow-up, six patients were taking treatment and were euthymic, we found a negative correlation with the YMRS and RRI at the bilateral orbitofrontal cortex (ρ = -0.8827, p = .019). They did not show significant improvement in cognitive performance at SCIP-S, and there was negative correlation with the following of the SCIP-S subscales; processing speed with the bilateral dorsolateral prefrontal, the bilateral medial prefrontal, the left temporal pole cortex RRI, and verbal fluency with the bilateral anterior cingulate cortex RRI. CONCLUSION: Cognitive impairment was correlated with brain perfusion patterns at baseline and follow-up. Large sample size studies with longer follow-up are needed to describe the changes in perfusion and cognitive functions in BD.

Differences in body mass index according to fat mass- and obesity-associated (FTO) genotype in Mexican patients with bipolar disorder.

OBJECTIVES: The prevalence of obesity has dramatically increased in many countries and it is particularly high in patients with bipolar disorder (BD). A region in the first intron of the fat mass- and obesity-associated (FTO) gene, encompassing markers rs9939973, rs8050136, and rs9939609, has been consistently associated with obesity and body mass index (BMI) in different populations. We sought to determine whether FTO is associated with BMI and/or obesity in patients with BD. METHODS: The sample included 129 Mexican Mestizo patients with bipolar I or bipolar II disorder. After obtaining informed consent, participants were evaluated with the Structured Clinical Interview for DSM-IV Axis I Disorders and weight, height, and body measurements were recorded. DNA was extracted from a 5-mL blood sample and real-time polymerase chain reaction was performed. The results were analyzed with Haploview v4.2 and SPSS v21. RESULTS: Differences in mean BMI were explained by rs8050136 and rs9939609 genotypes, especially by comparing non-carriers and carriers of two copies of the risk allele (Tukey's p ≤ 0.019), with a mean difference in BMI as high as 7.81 kg/m(2) . Differences in BMI were also explained by the interaction of the genotype (rs8050136 and/or rs9939609), the use of second-generation antipsychotics, and the use of mood stabilizers (p ≤ 0.41). Obesity was also associated with these two markers when patients with and without obesity were compared. CONCLUSIONS: In patients with BD, differences in BMI may be affected by the presence of FTO risk alleles, especially in homozygous individuals for these variants. Besides evaluating the possible metabolic effects of certain antipsychotics or mood stabilizers, it is important to evaluate the role of other factors such as FTO risk alleles.

Determinación de subtipos del virus respiratorio sincicial en muestras positivas por el virus, aisladas en el Hospital Nacional de Niños / Detection of human respiratory syncytial virus subtypes A and B in hospitalized children in Costa Rica

Objetivo: El virus respiratorio sincicial, VRS, es un pneumovirus de la familia Paramyxovridae, que causa enfermedad severa del tracto respitaroio inferior en neonatos y niños pequeños, especialmente en los primeros años de vida. Es responsable de constantes hospitalizaciones y visitas a los servicios de emergencias. Se han identificado dos subtipos: VRS-A y VRS-B, mediante anticuerpos monoclonales y técnicas moleculares. El objetivo de este estudio fue establecer por primera vez la circulación de ambos subtipos del VRS, en muestras positivas de niños hospitalizados durante el pico estacional de 2008, en el Hospital Nacional de Niños, HNN. Métodos: Se analizaron 49 muestras de aspirados nasofaríngeos de niños hospitalizados, de un total de 578, de las cuales 197 fueron previamente positivas para VRS por inmunofluorescencia directa. Se realizó cultivo celular, y un RT-PCR múltiple, estandarizado en el laboratorio, para detectar VRS-A y VRS-B. Resultados: La frecuencia del VRS fue del 34 por ciento en el HNN, para agosto y septiembre de 2008. De las 49 muestras analizadas por RT-PCR, 41, 84 por ciento, fueron positivas, 34, 83 por ciento, por el subtipo A y 7, 17 por ciento, por el B; 8 fueron negativas. Ningún paciente presentó infección mixta y no hubo diferencia entre los síntomas, la edad o el origen geográfico de los niños. El cultivo fue positivo solo en el 30 por ciento de las muestras. Conclusión: La frecuencia del VRS para el periodo en estudio fue del 34 por ciento de las muestras analizadas en aspirados nasofaríngeos. Este es el primer reporte de la detección de los subtipos A y B del VRS, en una pequeña cohorte del HNN, confirmados por un RT-PCR múltiple estandarizado en el laboratorio.

Immune variations in bipolar disorder: phasic differences.

OBJECTIVES: To characterize the immunological variations of patients with a bipolar disorder (BD) diagnosis in manic (BDm) and depressive (BDd) phases, by the quantification of the serum levels of interleukin (IL)-1beta, -2, -4, -6 and tumor necrosis factor alpha (TNF-alpha). METHODS: Twenty physically healthy patients with a BD type I diagnosis and 33 matched controls were studied, after giving informed consent. The inclusion criteria included at least three weeks without any kind of psychopharmacological treatment, Young Mania Rating Scale score > or =20 for BDm (n = 10) and Hamilton Depression Rating Scale score > or =21 for BDd patients (n = 10). Exclusion criteria included any infectious diseases, allergies or any other kind of medical illness that required treatment with immunosuppressors, as well as any other diagnosis in Axis I. Physical and laboratory examinations were performed to rule out any clinical illness. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum cytokines concentration. RESULTS: BD patients, when compared to controls, showed significant differences (p < or = 0.05) in the serum levels of the measured cytokines. The sub-group of BDd patients showed an increase in IL-6 and TNF-alpha, as well as a decrease in IL-2 concentration. The BDm sub-group, on the other hand, showed an increase in TNF-alpha and IL-4 values, with a low concentration of IL-1 and IL-2. The comparison between both sub-groups suggests that there is a distinctive cytokine pattern for the specific phases of the disorder: for mania, we found a high IL-4 and low IL-1beta and IL-6 concentration, while in the depressive phase, the inverse pattern was found. CONCLUSIONS: Our results show the existence of phasic differences in the serum levels of cytokines in BD.

La detección de casos de trastorno bipolar por medio de un instrumento de tamizaje: el Cuestionario de Trastornos del Animo versión en español

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Summary Bipolar spectrum disorder which includes bipolar I, bipolar II, ciclothymia and bipolar disorder, not otherwise specified often goes unidentyfied, underdiagnosed, or confounded with major depressive disorder. There are several considerations that try to explain this frequent omission. One crucial aspect is that, the first mood episode at onset is often a depressive one, and some bipolar patients present multiple depressive episodes prior to their first episode of mania. Additionally, long-term evaluation of patients with bipolar I or II disorders, reveal that depressive symptoms occur more common than manic or hypomanic symptoms. Another plausible explanation is that bipolar patients frequently underreport symptoms of mania. Thus it is not surprising to find that in many patients, may elapse about 10 years from the first time for they seek treatment until a clinician finally makes the correct diagnosis. As a consequence, such patients may suffer poorer outcomes, subsyndromal symptoms and a course of illness marked by more sever symptoms, chronic mood episodes, increased recurrence and more impaired psychosocial functioning. The correct diagnosis of bipolar disorder becomes an important and crucial issue, if it is considered that there is a current trend to understand better this affective illness as a spectral disorder. This concept helps to identify different subtle subtypes of bipolarity which often are unrecognized, by means of the actual diagnostic criteria. This diagnostic reformulation is based on the phenomenological manifestations of the entities, as well as in other specific clinical aspects, such as comorbidity, predominant episodes, genetic information and treatment response to among others. Thus, correct recognition of bipolar disorder will bring an important benefit to patients and may reduce erratic treatments and improve outcome. Several epidemiological studies report that the global prevalence of bipolar I disorder is around 1%, in the general population, but when considering all subtypes included in the bipolar spectrum, this lifetime prevalence increases up to 5%. As a consequence of an incorrect diagnosis, patients are often undertreated or receive an erroneous pharmacological treatment, mainly with antidepressants, which complicate outcome by promoting manic or hypomanic reactions and may have devastating consequences in the further clinical intents to stabilize the disorder. In order to increase the recognition of an illness, the correct utilization of a clinical screening procedure is mandatory. Several screening instruments exist for a variety of psychiatric disorders. However, only until recently, some of them have been developed specifically to identify bipolar disorders. The Mood Disorder Questionnaire, was the first screening instrument specifically developed to detect bipolar cases in clinical settings. It is a self-report, single-page, paper and pencil inventory than can be quickly and easily scored by a physician, a nurse or by trained medical staff assistance. It is composed of 13 questions which are answered with a positive or negative fashion, elaborated from the bipolar diagnostic criteria and clinical experience and inquires about possible manic symptoms. In the original report of its development and validation, it was concluded that it is a useful screening instrument for bipolar spectrum disorders, with a good sensitivity (0.73) and a very good specificity (0.90). Method: The questionnaire has been translated to other languages and has been used in non-clinical settings, with very good standards of performance. Since there is not a Spanish version of it, we decided to translate this instrument and to design a trial for the following purposes: 1) to obtain a validated and understandable Spanish version of the questionnaire. 2) To determine its sensibility and specificity in a sample of patients with affective disorders. 3) To identify its optimal cutoff score for screening purposes. The first step in our study consisted in the development of a translated version of the instrument. For that purpose a translation- retranslation procedure was utilized, in which four clinical psychiatrists with experience in treating bipolar patients made each one a separate translation. Then, all the versions were discussed until a consensus was reached in a final version. This version was retranslated to English and, after making some adjustments, the final version in Spanish was concluded. The study aimed to determine the clinimetric parameters of the Mood Disorder Questionnaire in its Spanish version, was conducted at the outpatient affective disorders clinic in the National Institute of Psychiatry Ramón de la Fuente, in México City. Patients with an age of 18 years and over who looked for psychiatric consultation, due to the presence of affective disorder were invited to participate. After explaining the procedure and the purposes of the study, all those who accepted to participate, signed 51 an informed consent document. This study was approved by the Ethical Committee of our institution. All patients completed the Mood Disorder Questionnaire. Two experienced clinical psychiatrists, blind to the questionnaire results, applied the Structural Clinical Interview for DSM-IV (SCID) to obtain the specific affective diagnosis in all the patients. Clinical and demographic data, as well as results from the clinical interview and questionnaire's scores, were obtained and then analyzed. Sensitivity and specificity for each Mood Disorder Questionnaire score, were plotted by using results from the SCID interview as a standard. Sensitivity (percent of criterion standard diagnosis correctly diagnosed by the questionnaire) and specificity (percent of criterion standard noncases correctly identified as noncases by the questionnaire) were obtained by using different symptoms, threshold that ranged from 5 to 10 points in order to determine the optimal screen threshold. Results: A total of 100 patients were included in the study. Mean age for the complete group was 35.3 years and 64% were female. According to the SCID results, 49 patients had a diagnosis within the bipolar spectrum disorder and 51 had a unipolar affective diagnosis. Each group included patients with both first and recurrent episodes, and with and without comorbidities. The questionnaire was completed by the total sample of patients covering the total range of answer's possibilities, from non-positive responses (1% of the sample) to 13 positive responses (15% of the sample). Mean score (± SD) was 8.06 (3.5) with a significant difference between patients in the bipolar group (10.3 ± 2.7) and patients in the unipolar group (5.8 ± 2.7); t = -8.2, 98 gl, p<0.001. Using different cutoff scores sensitivity and specificity were calculated, observing that with a 10 point cutoff score, equilibrated sensitivity (0.71) and specificity (0.92) levels were obtained. Conclusions: The study was aimed to obtain an adequate translated version into Spanish of the Mood Disorder Questionnaire, and to determine its sensitivity and specificity, according to an optimal cutoff score, for correctly detecting bipolarity from a sample of affective disorder patients. With a reliable procedure of translation process, we obtained a satisfactory, understandable and easy to use version for patients. Similar to other reports, a structured clinical interview was utilized to obtain the patients diagnoses. After evaluating with different cutoff scores, we found that a score of 10, gives an adequate distribution for levels of sensitivity and specificity. However, lower scores (between 7 and 9), also give adequate levels of sensitivity and specificity. It is important to consider, that our study was done in a very specific sample of patients who had only affective disorders. With these type patients it is necessary to raise the bar sufficiently to obtain adequate results. In other studies that included non-affective patients the questionnaire worked well with lower cutoff points. The operating characteristics of the Mood Disorder Questionnaire in its Spanish version are sufficiently good to consider its application as a reliable screening instrument for detecting bipolar spectrum disorders at least, in an affective disorders clinical setting. Further studies are needed to evaluate whether the instrument would be useful in other psychiatric settings as well as in community or primary care samples, and also to determine the best cutoff point depending in the characteristics of the population in which it is being used.