Infecciones en pacientes reumatológicos asociadas a corticosteroides y antagonistas del factor de necrosis tumoral α / Infections in patients affected by rheumatologic diseases associated to glucocorticoid use or tumor necrosis factor-alpha inhibitors

A great diversity of infectious agents can affect patients that use steroids at immunosuppressive doses or tumor necrosis factor α (TNF-α) antagonists. The list of participating microorganisms is more restricted in the case of anti TNF-α blockers. Overlapping agents include intracellular bacteria, Mycobacterium tuberculosis, geographic fungal agents that have the ability to establish granulamotous infections, herpes zoster, and reactivation of chronic hepatitis B virus infection. An important conceptual issue for these infections is the existence of a threshold prednisone daily dose for the emergence of opportunistic infections but higher levels of immunosuppression and cofactors are required in the case of Pneumocystis jiroveci and cytomegalovirus infections. In order to prevent these threats, a detailed medical evaluation is needed before prescription to detect potential risks and manage them properly. Prevention rules must be prescribed in every case, that include common sense behaviors, vaccines, and in selected cases, chemoprophylaxis for latent tuberculosis (TB) infection, P. jiroveci pneumonia (PCP) or other specific requirements. Latent TB infection is probable and requires chemoprophylaxis in the case of remote or recent exposure to a patient with lung TB, a positive tuberculin or interferon-gamma release assay result or residual lung scars in a chest x-ray exam. PCP prevention is suggested when the patient reaches a daily dose of prednisone of 30 mg but might be needed at lower doses in case of other concomitant immunosuppressive drugs or when lymphopenia arises shortly after prednisone initiation.

Una gran diversidad de agentes infecciosos puede afectar a los pacientes que usan corticosteroides en dosis inmunosupresoras o antagonistas del factor de necrosis tumoral o (FNTα). La lista de microorganismos participantes es más restringida en el caso de los bloqueadores del FNTα. Los agentes que se sobreponen incluyen bacterias intracelulares, Mycobacterium tuberculosis, hongos geográficos que son capaces de establecer infecciones granulomatosas, herpes zoster y reactivación de hepatitis crónica por virus de hepatitis B. Existe una dosis umbral diaria de prednisona (o equivalente), sobre la cual emergen estas infecciones oportunistas, pero el nivel de inmunosupresión parece ser más alto en el caso de Pneumocystis jiroveci o citomegalovirus. Para prevenir estas amenazas, se requiere una evaluación médica detallada antes de su prescripción para detectar riesgos potenciales y manejarlos apropiadamente. Se deben indicar medidas de prevención en cada caso, las que incluyen conductas de sentido común y en casos seleccionados, quimioprofilaxis para infección latente por tuberculosis (TBC), neumonía por P. jiroveci u otros requerimientos específicos. La existencia de TBC latente es probable en el caso de exposición reciente o remota a un bacilífero pulmonar, prueba de tuberculina o de liberación de interferón γ positiva, o lesiones residuales en la radiografía de tórax. La prevención de neumonía por P. jiroveci se recomienda cuando se usan al menos 30 mg de prednisona al día pero puede ser necesario a dosis menores si se aplican otros fármacos inmunosupresores concomitantes o si aparece linfopenia poco después del inicio de los corticosteroides.

Polymerase chain reaction techniques: applications in parasitic diseases

dNTPs: Nucleotides; ESTs: Expressed sequence tags; HAT-RAPD-PCR: High annealing temperature random amplified polymorphic DNA PCR; HSP: Heat shock protein; ITS: Internal transcribed spacer; mRNA: Messenger RNA; MSP: Merozoite suiface proteins; MT-PCR: Multiplex tandam PCR; PCR: Polymerase chain reaction; qPCR: Quantitative basic PCR; qRtime-PCR: Quantitative real-time PCR; qRT-PCR: Quantitative reverse transcriptase PCR; QT-NASBA: Quantitative nucleic acid sequence-based amplification; RAPD: Random amplified polymorphic DNA; RFLP: Restriction fragment length polymorphism; RNA: Ribonucleic acid; Rtime-PCR: Real time PCR; RT-PCR: Reverse transcriptase PCR; SNP: Single nucleotide polymorphism;TLRs: Toll-like receptors

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Consideraciones sobre la evolución de la respuesta inmunitaria Th2 y sus posibles relaciones con parasitosis y alergia / The evolution of the Th2 immune responses and its relationships with parasitic diseases and allergy

Hay diversos vínculos entre las parasitosis, especialmente las helmintiasis, y las enfermedades alérgicas, ambas condiciones de importancia epidemiológica en las regiones tropicales. Mientras que se ha especulado con frecuencia los efectos de las enfermedades parasitarias sobre la evolución del sistema inmunitario, no se conocen las fuerzas selectivas que han moldeado la respuesta alérgica y pensamos que incluyen mecanismos evolutivos distintos a los tradicionalmente divulgados. Los helmintos, fuente infecciosa y antigénica inductora de una respuesta parecida a la alérgica, se establecieron como parásitos en huéspedes que ya tenían grupos celulares de inmunidad de tipo 2. Hoy sabemos que un componente esencial en la relación de parasitismo entre los helmintos y sus huéspedes es la inmunosupresión que los primeros inducen, al crear una especie de equilibrio que permite la supervivencia de ambos. El desarrollo de este equilibrio debió incluir adaptaciones de ambos organismos y la supervivencia del parásito podría ser el resultado de la adquisición de mecanismos supresores de la respuesta defensiva, la selección de los huéspedes con menor intensidad de la respuesta de tipo 2, o ambas. Esto, a su vez, sugiere que aunque las infecciones helmínticas hayan influido en la conformación de la inmunidad de tipo 2, no han sido una fuerza selectiva importante en el caso particular de la respuesta alérgica que, a su vez, está más ligada a una exagerada respuesta Th2/IgE.

A variety of links occur between parasites, particularly helminths, and allergic diseases--both common conditions of epidemiological importance in tropical regions. Although speculations are often made about the effects of parasitic diseases on the evolution of the immune system, the selective forces that have shaped the allergic response are unknown and probably include evolutionary mechanisms different to those traditionally reported. Helminths, infectious and antigenic sources that induce allergic-like responses, established themselves as parasites in organisms that already had cell groups related to the type 2 immunity. An essential component in the relationship between helminths and their hosts is that the former induce immunosuppression, creating a kind of balance that allows the survival of both. The development of this equilibrium undoubtedly includes adaptations in both organisms, and the survival of the parasite is the result of (a) acquiring immune suppressor mechanisms and (b) finding hosts with lower intensity of the type 2 response. This in turn suggests that although helminth infections have influenced the formation of type 2 immunity, they have not been an important selective force in the particular case of allergic response. The latter is more related to an exaggerated Th2/IgE response.

Novel regulatory SNPs in the promoter region of the TNFRSF18 gene in a Gabonese population

Parasites are accountable for driving diversity within immune gene families. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the tumor necrosis factor receptor superfamily member 18 (TNFRSF18) gene by direct sequencing in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis. Two new promoter variants were identified in 40 individuals. Both novel variants were heterozygous and were linked to SNP #rs3753344 (C/T), which has been described. One of the SNP variants (ss2080581728) was close to the general transcription factor site, the TATA box. We further validated these new promoter variants for their allelic gene expression using transient transfection assays. One new promoter variant with two base changes (C/T - ss2080581728/rs3753344) displayed an altered expression of the marker gene. Both novel variants remained less active at the non-induced state in comparison to the major allele. The allele frequencies observed in this study were consistent with data for other African populations. The detection and analysis of these human immune gene polymorphisms contribute to a better understanding of the interaction between host-parasite and expression of Treg activity.

Enteroparasitoses em indivíduos HIV/aids: aspectos epidemiológicos, nutricionais e imunológicos / Intestinal parasites in HIV/AIDS: epidemiological, nutritional and immunological

O trato gastrointestinal desempenha papel critico na patogenia da aids sendo as alterações clinicas principalmente associados a parasitoses. O presente estudo avaliou as variáveis epidemiológicas, nutricionais e imunológicas nos indivíduos HIV positivos com e sementeroparasitoses. Foram avaliados 105 indivíduos, 54 (51,43) do sexo masculino. A média de idade dos não parasitados foi de 40,19 ± 10,39 anos e dos parasitados 44,15 ± 10,86. Todos foram atendidos no Serviço de Ambulatórios Especializados e Hospital Dia Professor Emérito Domingos Alves Meira em Botucatu/UNESP. Foi aplicado questionário socioeconômico, aferido peso e altura para cálculo de IMC e coletadas 3 amostras de fezes para exame parasitológico (método TFtest® ) e 5ml de sangue para avaliação de eosinófilos , albumina IgE, contagem de linfócitos TCD4+ e TCD8+ , carga viral e quantificação das citocinas TNF-alfa, INF-8, IL-2, IL-5 e IL-IO em ambos os grupos. Dentre os 105 indivíduos analisados, 92 (87,6) apresentaram resultados negativos para enteroparasitoses e 13 (12,38) resultados positivos. Entamoeba coli foi encontrada em 5 (38,5) das amostras, Giardia lamblia 4 (30,7), Blastocystis hominis 3 (23.0), Endolimax nana 2(15.4) e Ascaris lumbricoides 1 (7.7). A maioria dos indivíduos (97,15) apresentava bom nível de escolaridade, todos com saneamento básico, moradia em área urbana (95,23), com água e esgoto tratados, a minoria (26,66) fazendo uso de horta. Eutrofia e sobrepeso esteve presente em 50 e 31,39 respectivamente e a maioria ( 88,57) em uso de TARV...

Infecções parasitárias: diagnóstico imunológico de enteroparasitose / Parasital infection: immunologic diagnostic of enteroparasitosis

As enteroparasitoses são causas relevantes de agravos à saúde em paises onde as condições sócio-econômicas-culturais permitem a manutenção e disseminação de vários parasitas. O desenvolvimento de métodos de diagnóstico para a parasitologia é de fundamental importância no estabelecimento da etiologia das infecções para correta intervenção terapêutica. O diagnóstico imunológico tem sido muito empregado no laboratório clínico pela simplicidade, rapidez de execução e baixo custo operacional. No entanto, existem dificuldades para a padronização dos testes imunológicos em relação à memória imunológica e à semelhança entre os antígenos constituintes dos parasitos, restringindo seu uso no diagnóstico de algumas patologias. Atualmente, o que se observa, no que diz respeito ao diagnóstico imunológico de parasitoses intestinais, é a dificuldade de padronização destes por apresentarem baixa sensibilidade, especificidade, reprodutibilidade e custos elevados para o isolamento de antígenos e anticorpos. Após a realização desta revisão bibliográfica constatou-se, que dentre todas as técnicas utilizadas na rotina para imunodiagnóstico de parasitoses intestinais, o ELISA destaca-se como método de escolha por apresentar malhor especificidade e sensibilidade.

Immunogenetics and infectious diseases: special reference to the mayor histocompatibility complex

Many studies have tried to identify genetic markers for infectious diseases, some of them have focused on human leukocyte antigens (HLA). The products of HLA genes interact with surface-specific receptors of T lymphocytes, resulting in activation of the host's immune response. Association of bacterial, viral, parasitic and fungal infections with the host's HLA has been widely investigated. The type and strength of this association differs among distinct populations, as well as among racial and/or ethnic groups. The new molecular methods for the identification of the HLA alleles, and the resulting new nomenclature, have contributed to a better understanding of this system. Unfortunately, this information has not been adequately transmitted to clinicians, which hampers the understanding of the association between the HLA system and diseases. We revised relevant studies on the association of HLA genes with infectious diseases, demonstrating their importance in the pathogenic mechanisms, through increased susceptibility or protection against infections and their complications.

Pyogenic abscesses and parasitic diseases

Parasitic diseases which during their course in the host switch the immune system from a T helper 1 to a T helper 2 response may be detrimental to the host, contributing to granuloma formation, eosinophilia, hyper-IgE, and increased susceptibility to bacterial and fungal infections. Patients and animals with acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S. mansoni association has also been well documented. The association of tropical pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara infection has recently been described in the same context. In tropical countries that may be an interesting explanation for the great morbidity of bacterial diseases. If the association of parasitic infections and pyogenic abscesses and/or fungal diseases are confirmed, there will be a strong case in favor of universal treatment for parasitic diseases to prevent or decrease the morbidity of superinfection with bacteria and fungi

Cytokines and host response to infections diseases

Doença ou proteção é o resultado de uma interação entre o hospedeiro e o agente infeccioso. Mecanismos de defesa e de escape são finamente regulados e em algumas situações, como e o caso do choque séptico, a resposta de defesa e a deletéria são aspectos do mesmo processo. Citocinas são mediadores com um amplo espectro de atividades biológicas, desempenhando um papel central na regulação da resposta imune. O padrão de citocinas induzido no hospedeiro tem sido associado a controle ou progressão de doença em animais de experimentação e em humanos. Nesta revisão abordaremos alguns aspectos das citocinas relacionados à patogênese de determinadas doenças infecciosas

Eosinofilia asociada a helmintiasis en niños atentidos en el Hospital Escuela, Honduras / Eosinophilia associated to helminthiasis in children attended in the Hospital Escuela, Honduras

Con el propósito de determinar la frecuencia de las infecciones parasitarias asociadas a eosinofilia se estudiaron 51 niños atendidos en el Bloque materno Infantil del Hospital Escuela (HE) de abril a septiembre de 1998. Los niños se seleccionaron si presentaban eosinofilia superior a 10 por ciento o un valor absoluto mayor de 850 células/µL. El estudio de los pacientes incluyó historia clínica, examen directo, conteo de huevos y Baermann. La mediana de edad fue de ocho años (1 a 15 años), la mayoría (51 por ciento) procedente del área rural. Los niños mayores de cuatro años presentaron más de 80 por ciento de los casos de eosinofilia moderada y severa. En 45 por ciento (23 niños) se identificó por lo menos un geohelminto conocido por casos de eosinofilia moderada y severa. En 45 por ciento (23 niños) se identificó por lo menos un geohelminto conocido por causar eosinofilia y en el resto de identificó un problema neoplásico o alérgico (5.8 por ciento cada uno) o bien ninguna causa aparente (43.1 por ciento). Ascaris lumbricoides y Strongyloides stercoralis se identificaron con mayor frecuencia. Aunque no fue estadísticamente significativo, se observó una tendencia de mayor intensidad de eosinofilia a mayor severidad de la helmintiasis. Estos resultados indican que el conteo de huevos y el método de Baermann son herramientas útiles para estudiar al paciente eosinofílico en el HE

Histopathological and immunohistochemical studies of skeletal muscle in mice experimentally infected with schistosoma mansoni

Histopathological, histochemical and immunohistochemical studies were carried out on the skeletal muscles of mice experimentally infected with Schistosoma mansoni throughout 20 weeks post infection. Histopathological changes were detected from the 13th week post- infection in spite of absence of Schistosoma mansoni eggs. There were definite enzymatic changes dehydrogenase, non-specific esterase and acid and alkaline phosphatases. These changes started from the 14th week post-infection. S. mansoni immune complex deposits were detected in the muscles from the 9th week post infection. Positive correlation was found between the degree of immune complex deposition and histopathological and histochemical changes. The study confirmed the role of immune complex in the pathogenesis of skeletal muscle lesion in Schistosoma mansoni infection [schistosomal myopathy]

The eosinophils in parasitic infections

Local and peripheal eosinophilia is a common feature of many helminth infections that present large, non-phagocytable surfaces to the inmune system. The effect of the eosinophils on these organisms has been studied in the last 18 years using schistosoma mansoni, trichinella spiralis, and other helminths as models. The early infection causes a nonspecific inflammation rich in macrophages, lymphocytes and neutrophils that sets the stage for a subsequent inmune response. The predominant effector elements of the inmune response are anaphylactic antibodies, mast cells, and eosinophils. Mast cell products attract eosinophils and concentrate antibodies and complement-covered parasites by their Fc and/or C3c receptors and release oxygen radicals and/or preformed proteins on the helmith surface. The radicals alter molecules of the parasite and the proteins disrupt its tegument or cuticle. Occasionally, they may harm host cells. Eosinophils also phagocytize and harm extracellular trypanosoma cruzi and may play a role in the damage to the host heart tissue. The eosinophil response is regulated by eosinophilopoietic factors (interleukines [IL] 3 and 5, and granulocyte macrophage colony-stimulating factor) eosinophilotactic factors (C5a from complement, eosinophil chemotactic factor of anaphylaxis [ECF-A], histamine, platelet stimulating factor, and other ECFs from mast cells and basophils, and ECF from parasites), and eosinophiloactivating factors (IL-5 from Th2 lymphocytes, tumor necrosis factor from macrophages, antibodies, and complement components). Other phagocytic cells (macrophages and neutrophils) also exhibit important anti-helminthic activities