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OBJECTIVE To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

We have detected antibodies, in the sera of Chagas disease, Kala-azar and Mucocutaneous leishmaniasis patients, that bind multiple antigens shared between the three causative agents. The Chagas disease sera showed 98 to 100% positive results by ELISA when the Leishmania braziliensis and Leishmania chagasi antigens were used, respectively. The Kala-azar sera showed 100% positive results with Trypanosoma cruzi or L. braziliensis antigens by immunofluorescence assays. The antibodies in the sera of Mucocutaneous leishmaniasis patients showed 100% positive results by ELISA assays with T. cruzi or L. chagasi antigens. Furthermore, the direct agglutination of L. chagasi promastigotes showed that 95% of Kala-azar and 35% of Mucocutaneous leishmaniasis sera agglutinated the parasite in dilutions above 1:512. In contrast, 15% of Chagas sera agglutinated the parasite in dilutions 1:16 and below. Western blot analysis showed that the Chagas sera that formed at least 24 bands with the T. cruzi also formed 13 bands with the L. chagasi and 17 bands with the L. braziliensis. The Kala-azar sera that recognized at least 29 bands with the homologous antigen also formed 14 bands with the T. cruzi and 10 bands with the L. braziliensis antigens. Finally...

DNAs from bacteria and variety of nonvertebrate organisms, including nematodes, mollusks, yeasts, and insects, cause polyclonal activation of murine B lymphocytes. Similar studies have not been reported for bovine B cells, and to date no studies have reported mitogenic properties of protozoal DNA for any species. However, we and others have observed that protozoal parasite antigens can induce the proliferation of lymphocytes from nonexposed donors. Extending these studies, we now show that the mitogenic property of protozoal antigen preparations is in part attributable to parasite DNA and that Babesia bovis DNA is directly mitogenic for bovine B cells. DNase treatment of B. bovis extracts abrogated B. bovis-induced proliferation of peripheral blood mononuclear cells from nonexposed cattle. Like DNAs from other organisms that were mitogenic for murine B cells, B. bovis DNA is largely nonmethylated and induced a dose-dependent proliferation of bovine B cells, which was reduced upon methylation. Furthermore, B. bovis and E. coli DNAs enhanced immunoglobulin secretion by cultured B cells, inducing moderate increases in immunoglobulin G1 and stronger increases in immunoglobulin G2. Because certain nonmethylated CpG motifs present in bacterial DNA are known to stimulate proliferation of murine and human B cells...

Human protozoal infections are ubiquitous and occur worldwide. In many cases, antiprotozoal agents currently in use predate the modern antibiotic era. Despite the relative lag in development of new antiprotozoal agents, the 1990s have witnessed an increasing level of interest in these infections, inspired by international travel and immigration, a growing awareness of antiprotozoal drug resistance, and the significance of acute and recrudescent protozoal infections in immunosuppressed hosts. This review summarizes for nonclinician readers the past, present, and future therapies for common human protozoal infections, as well as pharmacologic mechanisms of action and resistance and common toxicities associated with these agents.

There exists in the mouse a family of I-region-controlled (Ia) antigens which carry carbohydrate-defined determinants. These antigens appear in serum as glycolipids and seem to be actively secreted by antigen-activated T-cells. This paper describes the ability of selected viral, bacterial, and protozoal infections of mice to markedly alter the serum levels of these Ia antigens. All the infectious agents examined induced substantial augmentation or suppression of serum Ia concentrations or both. Lymphocytic choriomeningitis (LCM) virus first enhanced and then suppressed serum Ia levels during the course of acute infection. Enhancement occurred during the time of ongoing virus replication and splenic lymphoproliferation while suppression coincided with the peak of the cytotoxic T-cell response and virus clearance. Listeria monocytogenes infection induced a substantial reduction in Ia levels at a time just after marked depletion of T-cells in the spleen. In contrast, Brucella abortus caused a significant increase in Ia levels 7 days postinfection, which correlates with the appearance of peak numbers of bacteria in tissues. Finally, Plasmodium yoelii, a nonlethal malarial parasite which stimulates prolonged T-cell proliferation, augmented serum Ia levels...

Bovine mononuclear cells in the presence of bovine anti-chicken erythrocyte sera at high dilutions induce release of chromium-51 from labeled chicken erythrocytes. Bovine effector cells are capable of recognizing both bovine immunoglobulin G1 and bovine immunoglobulin G2; in contrast, human effector cells only recognize immunoglobulin G1. Effector cell activity of bovine mononuclear cells is equally distributed between peripheral blood and spleen. As in other species, thymus and lymph node cells exert no antibody-dependent effect, although some direct cytotoxicity by lymph node cells may be observed. Antibody-dependent cell-mediated cytotoxicity against a bovine cell line can also be detected. By using a tannic acid technique, it was found that chicken erythrocytes coated with Theileria parva piroplasm antigen or with Trypanosoma rhodesiense variant-specific coat antigen form suitable targets for bovine antibody-dependent cell-mediated cytotoxicity assays. By using such targets, a moderate degree of direct cytotoxicity by bovine mononuclear cells, in the absence of antibody, is always observed; this may be reduced by choosing optimal conditions of tannic acid treatment and antigen sensitization and by the use of short incubation periods for the cytotoxicity assay. Observations have been made on the variant specificity...

Infections of Eimeria stiedae in normal and splenectomized rabbits and of Leishmania enriettii in normal rabbits and guinea-pigs and in splenectomized rabbits did not produce dye test antibodies. Guinea-pigs injected with Atoxoplasma sp. and rabbits immunized with cultures of Crithidia fasciculata were found to be negative for dye test antibodies. Mice which had been infected with Trypanosoma cruzi did not show dye test antibodies. All these animals, except one guinea-pig infected with Leishmania enriettii, were negative in the complement-fixation test for toxoplasmosis using the egg antigen. These findings are discussed in the light of previous reports.

Sarcocystis neurona causes serious neurological disease in horses and other vertebrates in the Americas. Based on epidemiological data, this parasite has recently emerged. Here, the genetic diversity of Sarcocystis neurona was evaluated using the amplified fragment length polymorphism (AFLP) method. Fifteen S. neurona taxa from different regions collected over the last 10 years were used; six isolates were from clinically diseased horses, eight isolates were from wild-caught opossums (Didelphis virginiana), and one isolate was from a cowbird (Molothrus ater). Additionally, four outgroup taxa were also fingerprinted. Nine primer pairs were used to generate AFLP patterns, with a total number of amplified fragments ranging from 30 to 60, depending on the isolate and primers tested. Based on the presence/absence of amplified AFLP fragments and pairwise similarity values, all the S. neurona isolates tested were clustered in one monophyletic group. No significant correlation could be found between genomic similarity and host origin of the S. neurona isolates. AFLP revealed significant intraspecific genetic variations, and S. neurona appeared as a highly variable species. Furthermore, linkage disequilibrium analysis suggested that S. neurona populations within Michigan have an intermediate type of population structure that includes characteristics of both clonal and panamictic population structures. AFLP is a reliable molecular technique that has provided one of the most informative approaches to ascertain phylogenetic relationships in S. neurona and its closest relatives...

Several interferon inducers (Newcastle disease virus, statolon, and poly rI:poly rC) as well as exogenous mouse interferon protect mice from sporozoite-induced Plasmodium berghei malaria, as long as they are administered before the end of the preerythrocytic phase of development of the parasite. The protective effect of the interferon inducers was related to their interferon-inducing effect; the protective effect of the interferon preparations was related to the interferon titer of the preparations, and it exhibited other attributes of interferon such as species specificity. In contrast to sporozoite-induced infection, blood forms-induced P. berghei malaria was only weakly susceptible to the protective effect of interferon inducers. This difference may provide an approach to study the mechanism of protection. The growth in cell cultures of another intracellular protozoon, Toxoplasma gondii, is also inhibited by interferon (22). The fact that P. berghei and T. gondii (as well as another group of intracellular parasites susceptible to interferon, the Chlamydia) have their own ribosomes raises questions, concerning the role of host cell ribosomes in the host cell-parasite relationship of these intracellular parasites and in the mechanism of interferon action against them...

Giardiasis is one of the most common intestinal protozoal infections worldwide. Although metronidazole is the most common drug used to treat giardiasis in humans, its use is associated with a variety of side effects. Poor compliance and the emergence of metronidazole-resistant strains may restrict use of the drug. Albendazole is an orally administered broad-spectrum anthelmintic agent. The use of albendazole has fewer side effects than metronidazole. The anthelmintic has been used against Giardia duodenalis both in vivo and in vitro with different results. However, the current meta-analysis assessed the effectiveness and safety of albendazole compared with metronidazole for the treatment of giardiasis in humans. After searching different databases, eight comparative randomized clinical trials, including 900 patients, met our criteria and were selected for the current meta-analysis. Results showed that albendazole was as effective as metronidazole for the treatment of giardiasis in humans and people receiving the drug tended to have fewer side effects compared with those who received metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug may be considered a potential alternative and/or a replacement for the existing widely used metronidazole in the treatment of giardiasis in humans.

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.

Enteric protozoan parasites remain the most commonly encountered parasitic diseases in HIV infected patients. Opportunistic protozoal infections that infect GIT most commonly and cause diarrhea in HIV-infected patients are cryptosporidium parvum, microsporidia and Isospora belli. Developing an infection with enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts associated with more severe, more atypical disease, and a greater risk of disseminated disease. We present histopathological features in a patient, where all three parasitic infections co-existed in HIV infected patient, who was under antitubercular therapy in addition to antiretroviral therapy and herpes zoster infection being treated by acyclovir.

A chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondii infection can prevent Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondii antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. berghei infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-γ). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-γ levels compared to those of mock-treated mice, suggesting that reductions in IFN-γ at the time of ECM onset protected against lethality. Using IL-10- and IL-12βR-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein...

Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast...

Bacteria (including chlamydia) and protozoa can produce neurological disease in Australian ruminant livestock and the nature of the inflammatory and neuroparenchymal response is often suggestive of a particular aetiological agent. An overview of the clinicopathological features of infectious disease affecting the central nervous system (CNS) is followed by a discussion of important bacterial and protozoal infections in Australia. Each infectious disease is discussed in terms of classification and pathogenesis linked to clinical signs and gross and microscopic findings. The literature review is restricted to infectious conditions causing CNS disease in Australia. Sources include the Australian Veterinary Journal (over 50 years of articles), the quarterly newsletter of the National Animal Health Surveillance System and the Animal Health Surveillance Quarterly.; AE Kessell, JW Finnie and PA Windsor

Protozoal infections that are efficiently transmitted by blood transfusion include Malaria, Chagas Disease, African Trypanosomiasis, Leshmaniasis, Toxoplasmosis and Babesiosis. With exception of Toxoplasmosis and Leishmaniasis, these diseases are endemic in mainly tropical low income countries and, in non-endemic countries like Portugal, the reported cases are imported from these endemic areas by travelers or immigrants. Globalization, with increasing travel and immigration poses the risk of exposition to these infectious agents and raises the issue of possible transmission by blood transfusion. According to recommendations of the Council of Europe, strategies to prevent the transmission of these infections by blood transfusion have been implemented. Given that the risk is introduced by a specific group of donors, travelers or immigrants from endemic areas, the main strategy to prevent this transmission depends on the identification of these groups of donors using questionnaires during the pre-donation procedures. Additional measures, like serological testing and pathogen inactivation procedures, when available, contribute not only to reduce the risk of transmission but also to avoid unnecessary rejections.; Protozoal infections that are efficiently transmitted by blood transfusion include Malaria...

Background: Immune reconstitution inflammatory syndrome (IRIS) is reported widely in patients initiating antiretroviral therapy (ART). However, few studies are prospective, and no study has evaluated the impact of the timing of ART when allocated randomly during an acute opportunistic infection (OI). Methodology/Principal Findings: A5164 randomized 282 subjects with AIDS-related OIs (tuberculosis excluded), to early or deferred ART. IRIS was identified prospectively using pre-defined criteria. We evaluated associations between IRIS and baseline variables in subjects with follow-up on ART using Wilcoxon and Fisher's exact tests, logistic regression, and Cox models with time-varying covariates. Twenty of 262 (7.6%) subjects developed IRIS after a median of 33 days on ART. Subjects with fungal infections (other than pneumocystis) developed IRIS somewhat more frequently (OR = 2.7; 95% CI: 1.02, 7.2; p-value = 0.06 (using Fisher's exact test)). In Cox models, lower baseline and higher on-treatment CD4+ T-cell counts and percentage were associated with IRIS. Additionally, higher baseline and lower on-treatment HIV RNA levels were associated with IRIS. Corticosteroids during OI management and the timing of ART were not associated with the development of IRIS. Implications: In patients with advanced immunosuppression and non-tuberculous OIs...

The acquired immunodeficiency syndrome (AIDS) is a devastating new disease caused by the human immunodeficiency virus (HIV). This retrovirus causes profound immunoincompetence in its infected hosts, who are thereafter susceptible to develop myriad severe and relapsing protozoal, fungal, bacterial, viral, and arthropodal opportunistic infections, as well as unusual malignancies. The more than 50,000 patients who have developed AIDS in the United States have produced a sudden unexpected deluge of diagnostic dilemmas that are stressing laboratories of pathology everywhere. This paper describes the gross and microscopic pathology of the numerous complications in patients infected by HIV: (a) the prodromal AIDS-related complex with persistent generalized lymphadenopathy, (b) lymphoid infiltration of salivary gland and lung, including the complex of lymphoid interstitial pneumonitis-pulmonary lymphoid hyperplasia, (c) extranodal non-Hodgkin's lymphomas, (d) multifocal mucocutaneous and visceral Kaposi's sarcoma, (e) small cell undifferentiated (oat cell) carcinomas, (f) protozoal infections caused by Pneumocystis carinii, Toxoplasma gondii, Acanthamoeba, Cryptosporidium species (sp.), and Isospora belli, (g) the causes of chronic enteritis...

Protozoal infections, though endemic to certain regions, can be seen all around the world, because of the increase in travel and migration. In addition, immunosuppression associated with various conditions, particularly with HIV infection, favors the occurrence of more severe manifestations and failure to respond to treatments. The CNS may be the only affected system; when not, it is often the most severely affected. Despite information obtained from clinical, laboratory, and imaging procedures that help to narrow the differential diagnosis of intracranial infections, there are cases that need confirmation with biopsy or autopsy. Predominant presentations are meningoencephalitis (trypanosomiasis), encephalopathy (cerebral malaria), or as single or multiple pseudotumoral enhancing lesions (toxoplasmosis, reactivated Chagas' disease). The immune reconstitution disease, resulting from enhancement of pathogen-specific immune responses after HAART, has altered the typical presentation of toxoplasmosis and microsporidiosis. In this paper, a morphological approach for the diagnosis of protozoal infections affecting the CNS (amoebiasis, cerebral malaria, toxoplasmosis, trypanosomiasis, and microsporidiosis) is presented.

Foram detectados anticorpos, nos soros de pacientes com doença de Chagas, Calazar e Leishnnaniose cutâneo-mucosa, que se ligam a antígenos compartilhados pelos três agentes causais. Os pacientes chagásicos mostraram 98 a 100% de soropositividade pelo ELISA quando antígenos de Leishmania braziliensis e de Leishmania chagasi foram usados, respectivamente. Os soros de Calazar mostraram resultados positivos com antígenos de Trypanosoma cruzi ou com L. braziliensis pela imunofluorescência. Ademais, os anticorpos nos soros de pacientes com Leishmaniose cutâneo-mucosa tinham 100% de resultados positivos pelo ELISA com antígenos de T. cruzi ou de L. chagasi. Ademais, a aglutinação direta de promastigotas de L. chagasi mostrou que 95% dos soros de Calazar e 35% de Leishmaniose cutâneo-mucosa algutinaram o parasito em diluições acima de 1:512. Em contraste, 15% dos soros chagásicos aglutinaram o parasito na diluição de 1:16 ou abaixo. Análises pelo Western blot mostraram que os soros chagásicos que formaram pelo menos 24 bandas com antígeno de T. cruzi também foramaram 13 bandas com antígeno de L. chagasi e 17 bandas com L. braziliensis. Os soros de Calazar que reconheceram pelo menos 29 bandas com o antígeno homólogo também formaram 14 bandas com o T. cruzi e 10 bandas com L. braziliensis. Finalmente...