Background The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum ( Tp ) to escape immune recognition while simultaneously inducing inflammation. Methods To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a combination of flow cytometry, immunohistochemistry (IHC), and transcriptional profiling to study the immune response in the blood and skin of 27 HIV(-) SS patients in relation to spirochetal burdens. Ex vivo opsonophagocytosis assays using human syphilitic sera (HSS) were performed to model spirochete-monocyte/macrophage interactions in vivo . Results Despite the presence of low-level spirochetemia, as well as immunophenotypic changes suggestive of monocyte activation, we did not detect systemic cytokine production. SS subjects had substantial decreases in circulating DCs and in IFNγ-producing and cytotoxic NK-cells, along with an emergent CD56−/CD16+ NK-cell subset in blood. Skin lesions, which had visible Tp by IHC and substantial amounts of Tp -DNA, had large numbers of macrophages (CD68+), a relative increase in CD8+ T-cells over CD4+ T-cells and were enriched for CD56+ NK-cells. Skin lesions contained transcripts for cytokines (IFN-γ, TNF-α), chemokines (CCL2, CXCL10), macrophage and DC activation markers (CD40, CD86), Fc-mediated phagocytosis receptors (FcγRI, FcγR3), IFN-β and effector molecules associated with CD8 and NK-cell cytotoxic responses. While HSS promoted uptake of Tp in conjunction with monocyte activation, most spirochetes were not internalized. Conclusions Our findings support the importance of macrophage driven opsonophagocytosis and cell mediated immunity in treponemal clearance, while suggesting that the balance between phagocytic uptake and evasion is influenced by the relative burdens of bacteria in blood and skin and the presence of Tp subpopulations with differential capacities for binding opsonic antibodies. They also bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response.
BackgroundThe diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases.Methodology/Principal FindingsSamples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml).Conclusions/SignificanceThe molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic patients highlight its possible relationship to the chronicity of the disease.
Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18–68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer ≥1∶4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5–240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.
El Grupo para el Estudio de la Resistencia Nosocomial en Colombia está conformado por las siguientes ciudades, hospitales y personas. Bogotá: Hospital Central de la Policía: Henry Mendoza, Flor Ángela Cubides, Martha Patricia Meléndez, Luz Angélica Quintero, Alba Lucía Sanín, Nancy Botia, Sandra Reina; Hospital Santa Clara: Beatriz E. Porras, Guillermo Ortiz, Luz Mila López; Hospital Militar Central: Henry Oliveros, María Nilse González, Ángela Pescador, Mónica Ballesteros, Sandra Valderrama, Alirio Rodríguez, Héctor Posso, Gloria Gallo, Fernando Guzmán, Jairo Pérez. Medellín: Hospital Pablo Tobón Uribe: Carlos Ignacio Gómez, Jaime López, Jorge Donado, Mónica Cuartas, Ana Lucía Correa, Lina Marcela Castañeda; Clínica Las Américas: Julián Betancourth, Juan David Villa, Jorge Nagles, Ana Cristina Quiroga, Nancy Estella González, Magda Orjuela, Rodrigo Agudelo; Hospital General Introducción. La resistencia a antimicrobianos se ha identificado como uno de los mayores problemas de salud pública, por lo cual debe ser vigilada permanentemente a través de sistemas efectivos de vigilancia. Objetivo. Describir el comportamiento de la resistencia antimicrobiana de bacilos Gram negativos, en las instituciones hospitalarias pertenecientes al Grupo para el Estudio de la Resistencia Nosocomial en Colombia, de enero 2006 a diciembre 2008. Materiales y métodos. Es un estudio descriptivo realizado con la información de los perfiles de sensibilidad bacteriana suministrada por 14 hospitales de tercer nivel en siete ciudades de Colombia, definidos como el Grupo para el Estudio de la Resistencia Nosocomial en Colombia, de enero de 2006 a diciembre de 2008. Usando el software WHONET 5.4, se describe el comportamiento de la resistencia bacteriana de las especies de Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae y Enterobacter cloacae) y bacilos Gram negativos no fermentadores (Pseudomonas aeruginosa y Acinetobacter baumannii) frente a antibióticos seleccionados como marcadores de resistencia en salas generales y unidades de cuidados intensivos de pacientes adultos. Resultados. En algunas Enterobacteriaceae se observó disminución de la frecuencia de resistencia antimicrobiana, mientras que P. aeruginosa se consolida como un germen multirresistente, cuyas frecuencias de resistencia continúan en aumento. Conclusiones. Los programas de vigilancia pueden tener un impacto en la disminución significativa de gérmenes multirresistentes, ya que contribuyen a la adecuada implementación de protocolos encaminados a fortalecer las estrategias de control de infecciones y el manejo racional de antibióticos en cada hospital. Antimicrobial resistance of Gram negative bacilli isolated from terciary-care hospitals in ColombiaIntroduction. Antimicrobial resistance has been identified as one of the major public health problems worldwide. To facilitate its control, bacterial resistance levels must be monitored permanently by effective surveillance systems. Objective. To describe the antimicrobial resistance patterns of Gram negative bacilli in ...
Introduction. Recent studies have suggested an association between the soil-transmitted helminth infections and malaria incidence. However, published evidence is still insufficient and diverging. Since 1977, new ecologic studies have not been carried out to explore this association. Ecologic studies could explore this correlation on a population level, assessing its potential importance on public health. Objectives. The aim of this evaluation is to explore the association between soil-transmitted helminths prevalence and malaria incidence, at an ecologic level in Colombia. Materials and methods. Using data from the National Health Survey, which was carried out in 1980 in Colombia, we calculated Spearman correlation coefficients between the prevalence of: Ascaris lumbricoides, Trichuris trichiura and hookworm, with the 1980 malaria incidence data of the same year provided from the Colombian Malaria National Eradication Service. A robust regression analysis with least trimmed squares was performed. Results. Falciparum malaria incidence and Ascaris lumbricoides prevalence had a low correlation (R 2 = 0.086) but this correlation was stronger into the clusters of towns with prevalence of Ascaris lumbricoides infection above 30% were only included (R 2 = 0.916). Conclusion. This work showed an ecologic correlation in Colombia between malaria incidence and soiltransmitted helminths prevalence. This could suggest that either there is an association between these two groups of parasites, or could be explained by the presence of common structural determinants for both diseases.
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