Pneumocystis jirovecii Colonization in Mexican Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of colonization by Pneumocystis jirovecii (P. jirovecii) has not been studied in Mexico. We aimed to determine the prevalence of colonization by P. jirovecii using molecular detection in a population of Mexican patients with chronic obstructive pulmonary disease (COPD) and describe their clinical and sociodemographic profiles. We enrolled patients discharged from our hospital diagnosed with COPD and without pneumonia (n = 15). The primary outcome of this study was P. jirovecii colonization at the time of discharge, as detected by nested polymerase chain reaction (PCR) of oropharyngeal wash samples. The calculated prevalence of colonization for our study group was 26.66%. There were no statistically significant differences between COPD patients with and without colonization in our groups. Colonization of P. jirovecii in patients with COPD is frequent in the Mexican population; the clinical significance, if any, remains to be determined. Oropharyngeal wash and nested PCR are excellent cost-effective options to simplify sample collection and detection in developing countries and can be used for further studies.

Genetic and Morphological Identification of Spirometra decipiens in Snakes and Domestic Dog Found in Cuba.

Spirometra (Cestoda: Diphyllobothriidea) affects humans and some species of domestic and wild animals which eventually interact with humans. In this article, we report three new cases of Spirometra decipiens (Diesing, 1850) infection observed in two intermediate hosts and one definitive host, in Cuba. Genetic and morphological identification of S. decipiens in two snakes and a domestic dog were carried out by molecular means and routine histological study using hematoxylin-eosin staining, respectively. Taken together, the anatomical location, the host species infected with the specimens and their morphological and genetic features, all the samples were identified as S. decipiens. In each of the three cases, PCR assays using specific primers amplified bands that corresponded to S. decipiens species. To our knowledge, this paper is the first report of S. decipiens in species of Cuban endemic fauna and in the Caribbean islands. These species constitute a real or potential risk of transmission of Spirometra to humans in Cuba.

A prevalence study in Guadalajara, Mexico, comparing tuberculin skin test and QuantiFERON-TB Gold In-Tube.

BACKGROUND: Tuberculosis (TB) is a prevalent disease throughout the world. The extent of TB illness in childhood is not clear; recent data shows that 10-20% of the cases are found in children under 15 years old. In 2017, 1 million children developed the disease, of which 9% were co-infected with HIV. METHODS: A cross-sectional study that analyzed 48 children diagnosed with HIV-infection in Guadalajara, Mexico. The tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT) were performed and compared to diagnose latent TB infection (LTBI). RESULTS: The average age was 9 years old (± 4), with an age range of 1-16 years; the 6-12-year-old group predominated with 50% of cases. 27 patients (56%) were male; 83% had received the BCG vaccination and 23% had a history of being contacts of TB cases. In the study, 40 patients (83%) were without immunosuppression; seven (15%) with moderate immunosuppression, and only one patient had severe immunodeficiency. Overall, 3 of the 48 children (6.2%) had a positive TST, while 8 out of 48 (16.6%) had a positive QFT. The concordance between the two tests was 89.6% (43/48) with Kappa = 0.5 (95% CI, 0.14-0.85). CONCLUSIONS: The QFT test represents an opportunity in the diagnosis of LTBI, particularly in pediatric HIV- patients. This is the first study that compares the two tests (TST and QFT) in children with HIV-infection in Guadalajara, Mexico.

Multilocus Genotyping of Pneumocystis jirovecii from Deceased Cuban AIDS Patients Using Formalin-Fixed and Paraffin-Embedded Tissues.

The results of the genotypic characterization of Pneumocystis jirovecii are described in lung tissue samples from 41 Cubans who died of AIDS with pneumocystosis between 1995 and 2008. Histological sections of the lung preserved as formalin-fixed and paraffin-embedded tissue were examined. PCR amplification and nucleotide sequencing of the two mitochondrial genes (large and small) of the pathogen allowed verification of a predominance of genotype 3 (85T/248C) of the large mitochondrial gene and genotype 3 (160A/196T) of the small mitochondrial gene over a period of 14 years (1995-2008). These results suggest that the 85T/248C//160A/196T genotype circulates with the highest frequency (81.3%) among AIDS patients in Cuba. Multilocus analysis indicates a limited circulation of pathogen genotypes on the island with the existence of a clonal genotype with an epidemic structure. Furthermore, it appears that circulating strains of P. jirovecii have not developed mutations related to sulfonamide resistance. Taken together, the data in this study revealed important elements about pneumocystosis in Cuban patients dying of AIDS and the usefulness of formalin-fixed and paraffin-embedded samples to carry out molecular epidemiology studies of P. jirovecii.

Utilidad de la prueba de la lactato deshidrogenasa en fallecidos cubanos con sida y neumonía por Pneumocystis jirovecii

RESUMEN Introducción: La neumonía por Pneumocystis jirovecii es una de las enfermedades de mayor impacto negativo en los pacientes con sida. La imposibilidad de cultivar el agente que la provoca, así como su cuadro clínico inespecífico y el alto costo de los métodos diagnósticos moleculares, señalan la necesidad de otras alternativas para su diagnóstico. La prueba de la lactato deshidrogenasa representa una opción a considerar. Objetivo: Demostrar la utilidad de la prueba de la lactato deshidrogenasa como diagnóstico de la Pneumocystis jirovecii en fallecidos cubanos por sida. Métodos: Se realizó un estudio de casos y controles (25 casos [Pneumocystis jirovecii] y 30 controles [compuestos por tres grupos: tuberculosis, linfoma y neumonía bacteriana, respectivamente]) en fallecidos cubanos a los que se realizó la autopsia desde enero de 1996 a diciembre de 2016. Se utilizaron cinco rangos de corte para buscar el valor óptimo de la prueba. Resultados: En el presente estudio existen diferencias altamente significativas entre los pacientes analizados (casos y controles) y entre los restantes individuos que componen los controles con respecto al del linfoma. El rango de corte óptimo para la prueba de la lactato deshidrogenasa fue (550-<800 U/I) con sensibilidad de 80 % y especificidad de 63 %. La razón de disparidad (OR) demostró que existe 6,91 veces más probabilidades que los pacientes por Pneumocystis jirovecii tengan las cifras de LDH mayor que los pacientes controles. Conclusiones: Este trabajo aporta evidencias científicas del rol de la prueba de la lactato deshidrogenasa como herramienta complementaria para el diagnóstico de la Pneumocystis jirovecii.

ABSTRACT Introduction: Pneumocystis jirovecii pneumonia is one of the diseases causing the greatest negative impact on AIDS patients. The impossibility of culturing its causative agent, its unspecific clinical presentation and the high cost of molecular diagnostic methods, make it necessary to find other diagnostic alternatives. The lactate dehydrogenase test is an option to be considered. Objective: Demonstrate the usefulness of the lactate dehydrogenase test to diagnose Pneumocystis jirovecii in Cuban patients deceased with AIDS. Methods: A case-control study was conducted (25 cases [Pneumocystis jirovecii] and 30 controls [distributed into three groups: tuberculosis, lymphoma and bacterial pneumonia, respectively]) of Cuban deceased patients undergoing post-mortem examination from January 1996 to December 2016. Five cutoff ranges were used to find the optimal value of the test. Results: Highly significant differences were found between the patients analyzed (cases and controls) and between the remaining individuals making up the controls with respect to the one with lymphoma. The optimal cutoff range for the lactate dehydrogenase test was 550-<800 U/I, with 80% sensitivity and 63% specificity. The odds ratio (OR) showed that probabilities are 6.91 times greater that Pneumocystis jirovecii pneumonia patients have higher LDH figures than control patients. Conclusions: Scientific evidence is contributed of the role of the lactate dehydrogenase test as a complementary tool in the diagnosis of Pneumocystis jirovecii.

Virulence Plasmids of Rhodococcus equi Isolates From Cuban Patients With AIDS.

Rhodococcus equi is an animal pathogen and zoonotic human opportunistic pathogen associated with immunosuppressive conditions. The pathogenicity of R. equi is linked to three animal host-associated virulence plasmids encoding a family of "Virulence Associated Proteins" (VAPs). Here, the PCR-based TRAVAP molecular typing system for the R. equi virulence plasmids was applied to 26 R. equi strains isolated between 2010 and 2016 at the Institute of Tropical Medicine "Pedro Kourí," Cuba, from individuals living with HIV/AIDS. TRAVAP detects 4 gene markers, traA common to the three virulence plasmids, and vapA, vapB, and vapN specific to each of the host-associated plasmid types (equine pVAPA, porcine pVAPB, and ruminant pVAPN). Of the 26 isolates, six were positive to the vapB (porcine-type) marker, 4 (15.4%) to the vapA (equine-type) marker, and 1 (3.8%) to the vapN (ruminant-type) marker. Most of the isolates 14 (53.8%) were negative to all TRAVAP markers, suggesting they lacked a virulence plasmid. To our knowledge, this work is the first to report the molecular characterization of R. equi isolates from Cuba. Our findings provide insight into the zoonotic origin of R. equi infections in people and the potential dispensability of the virulence plasmid in immunosuppressed patients.

Infección tuberculosa latente en niños de riesgo / Latent tuberculosis infection in children at risk

Introducción: En países de baja prevalencia la mayoría de los casos de tuberculosis se deben a reactivación de infección tuberculosa latente. Objetivo: Examinar la incidencia de infección tuberculosa latente en niños pertenecientes a grupos vulnerables a la tuberculosis. Métodos: Se realizó un estudio descriptivo, transversal y prospectivo en 85 menores de 19 años asintomáticos, 68 pertenecientes a algunos grupos vulnerables a la tuberculosis atendidos en el Hospital Pediátrico Centro Habana y en el Instituto de Oncología y Radiobiología y un grupo control de 17 adolescentes sanos, provenientes de la Escuela de Enfermería de la Facultad Calixto García, periodo abril-junio 2016. A todos se les realizó examen clínico, evaluación nutricional, radiología torácica y prueba de tuberculina. Resultados: De los 85 estudiados, 41 padecían enfermedades crónicas: 12 diabéticos, 11tenían enfermedad del colágeno, 9 enfermedad renal crónica y 9 enfermedades oncológicas. Todos tenían más de un año de evolución y recibían medicación inmunosupresora (excepto los diabéticos). De los 44 restantes, 27 tuvieron contacto estrecho y frecuente con enfermo de tuberculosis. Predominaron los niños ≥ 10 años (64; 75,3 por ciento), del sexo femenino (49; 57,6 por ciento). Todos estaban vacunados con BCG, con radiografías torácicas normales. Se detectó infección tuberculosa latente en 6 (7,0 por ciento); todos habían estado en contacto con un enfermo. Conclusiones: Existe una baja incidencia de infección tuberculosa latente en los grupos vulnerables estudiados. Los niños en contacto con enfermos son los únicos afectados, lo que puede estar relacionado con la baja tasa de tuberculosis en Cuba y las rápidas acciones de control(AU)

Introduction: Most of the tuberculosis cases in countries with low prevalence of it are due to a reactivation of the latent tuberculosis infection. Objective: To examine the incidence of the latent tuberculosis infection in children of groups vulnerable to tuberculosis. Methods: It was conducted a descriptive, cross-sectional and prospective study in 85 asymptomatic children under 19 years, 68 of them from some groups vulnerable to tuberculosis that were attended in Centro Habana Pediatric Hospital and in the Oncology and Radiobiology Institute; and a control group of 17 healthy adolescents from the Nursing School of Calixto García Faculty, in the period April-June, 2016. All patients underwent a physical examination, nutritional assessment, thoracic radiology and tuberculin test. Results: From the 85 patients studied, 41 suffered chronic diseases: 12 diabetics, 11 had collagen disease, 9 had chronic renal disease and other 9 have oncologic diseases. All patients had an evolution of more than one year and were receiving immunosuppressive medication (except from the diabetics). From the other 44 patients, 27 had close or frequent contact with a tuberculosis patient. There was predominance of children ≥ 10 (64; 75,3 percent) of the female sex (49; 57,6 percent). All of them were vaccinated with BCG and had normal thoracic radiographies. It was detected latent tuberculosis infection in 6 patients (7,0 percent); all of them had had contact with a tuberculosis sufferer. Conclusions: There is low incidence of latent tuberculosis infection in the studied vulnerable groups. Children having contact with tuberculosis sufferers are the only affected, which can be related with the low rate of tuberculosis in Cuba and the fast control actions(AU)

Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The -794 CATT5-8 and -173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.

Short (GT)n microsatellite repeats in the heme oxygenase-1 gene promoter are associated with antioxidant and anti-inflammatory status in Mexican pediatric patients with sepsis.

An adequate immune and antioxidant response is a key to the resolution of sepsis. Heme oxygenase-1 (HMOX1) is a stress protein with a polymorphic (GT)n repeat in its gene promoter that regulates its expression in response to oxidative injury, such as that present in sepsis. HMOX1 is the rate-limiting enzyme of heme degradation, and the heme breakdown products, CO, Fe, and bilirubin, are considered to be biologically active metabolites with direct or indirect antioxidant and anti-inflammatory properties. In this study, we investigated the inflammatory and antioxidant response and the relationship with the HMOX1 levels and HMOX1 polymorphism in Mexican septic pediatric patients. In a case-control pilot study, we enrolled 64 septic patients and 72 hospitalized control patients without a diagnosis of sepsis. DNA extracted from buffy coat was genotyped for HMOX1 (GT)n polymorphism by PCR and markers of antioxidant and inflammatory status were quantified in plasma by analysis of the oxygen radical absorbance capacity (ORAC), protein carbonyl (PC), interleukin (IL) 6, IL10, and HMOX1 levels. In septic children, oxidative and inflammatory markers were elevated, and HMOX1 levels were positively correlated with IL10 levels. Genotypic and allelic distribution of HMOX1 polymorphism showed no difference between groups. HMOX1 short-allele septic carriers (< 25 GT repeats) presented favorable ORAC, PC and IL10 levels. This study confirms that an active response against pediatric sepsis involves the expression of HMOX1 and IL10, suggesting that the high antioxidant status associated with HMOX1 short-allele septic carriers might provide a beneficial environment for sepsis resolution.

Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil.

BACKGROUND: Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil. METHODS: We used case-series and case-control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records. RESULTS: We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case-control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico--an increase by a factor of 1.9 to 2.6 - was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries. CONCLUSIONS: RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).

Interleukinas y embarazo: una realidad cuestionada / Interleukines and pregnancy: a questioned reality

Se revisa la literatura relacionada con el papel que juegan las Interlukinas (ILs) en el embarazo puntualizándose que en el mecanismo de trabajo de parto espontáneo están involucradas estas substancias, las cuales actúan como disparadores de la cascada ácido araquidónico/prostaglandina; este mismo proceso puede activarse por lipopolisacárdios bacterianos implicados en la etiología del parto pretérmino. Normalmente la producción y actividad de la IL-2 esta inhibida para que el embarazo siga un curso normal, si esto no sucede se tendrían problemas de aborto de repetición, la IL-3 conjuntamente con factores estimuladore de crecimiento (FECs) permite el adecuado crecimiento del producto de la gestación si esto se altera habría retardo en el crecimiento intrauterino; a,bas interleukinas actúan a nivel de la interfase materno fetal. Por lo anterior es importante que el ginecoloobstetra tenga una información básica relacionada con ILs y su relación con el embarazo normal y complicado