Santo Inácio revisited: protozoan diseases in an isolated village in northeastern Brazil after twenty years

The northeastern highlands of Brazil are endemic for several tropical diseases, especially American trypanosomiasis (Chagas' disease) and schistosomiasis. Twenty years ago, we measured the seroprevalence of protozoan diseases in Santo Inácio, a village of approximately 1,000 inhabitants located 1,000 m above sea level. We detected small numbers of sera with antibodies against Trypanosoma cruzi and Toxoplasma gondii, and the area had a low prevalence both of American trypanosomiasis (3.54%) and toxoplasmosis (27.43%) compared with nearby Brazilian areas. This was attributed to a specific triatomine vector and local housing conditions. Twenty years later, we again determined the prevalences of both diseases and compared these results with those from Iraquara, a larger town with the same ethnic and social background but with a higher prevalence of rural activities. The incidence of Chagas' disease in San Inácio showed the same low level, i.e., 3.78% (5 of 132) with only adult males affected in contrast with Iraquara, which had an incidence of 34.5%, but a low prevalence of only one of 22 among children up to 14 years of age. Santo Inácio maintained a low (25.8%) seroprevalence for toxoplasmosis. Housewives presented a higher incidence of toxoplasmosis during both periods, probably due to related risk factors. Cats were found less frequently in Santo Inácio than in Iraquara, which showed an incidence of 65.5% seropositivity for Toxoplasma gondii. These results suggest that the environmental conditions of Santo Inácio were preserved after 20 years, with a low incidence of these selected protozoan diseases.     

The complement profile in babesiosis

Rats have been infected with Babesia rodhaini, a protozoan agent that induces immune complex disease. Assays for complement have revealed depletion of C2, C3, C4, C5, and whole complement in the course of infection. No evidence of depletion in the alternative (properdin) pathway was found. These findings are consistent with the conclusion that the classical complement pathway is activated during the course of the protozoan infection.     

Entamoeba histolytica: signaling through G proteins

The intracellular signaling pathways of Entamoeba histolytica are largely unknown. Although the expression of guanine nucleotide binding proteins (G proteins) is expected from functional studies, their biochemical characterization remains elusive in this protozoan. Using a combination of biochemical and immunological studies, we provide strong evidence for the presence of a Gs protein in amoeba. Our results strengthen our understanding of the signal transduction mechanisms in E. histolytica as potential sites of a new therapeutic strategy.     

Pathogenesis of enteric diseases

The pathogenesis of digestive disease in poultry involves the cellular events and reactions that result in a deviation from normal structure and function. To a degree, the differentiation of disease and normal in commercial poultry also involves an economic perspective. Factors external to the digestive tract may mimic digestive disease, including reductions in the density of various nutrients and feed refusal. Antinutritional factors, such as certain storage polysaccharides and proteins, are inaccessible to endogenous enzymes and are either indigestible or act as blockers of the digestion of other nutrients. Changes in digestive secretions that result in either excess or deficiency also influence digestive structure and function. Infectious agents and toxins that cause degeneration and necrosis are especially injurious because a series of critical repair events must occur in order to regain function. The consequences range from lethal injury of the host animal to diminished performance. The digestive tract has a large component of lymphoid tissue and impairment of the immune system influences the course of protozoan, bacterial and viral enteric diseases.     

Gap junction disappearance in astrocytes and leptomeningeal cells as a consequence of protozoan infection

Trypanosoma cruzi and Toxoplasma gondii are protozoan parasites capable of causing infections of the nervous system. In order to determine effects of infection by these organisms on intercellular communication in the brain, dye coupling and connexin abundance and distribution were examined in leptomeningeal cells and astrocytes infected with T. cruzi or T. gondii. For both cell types infected with either type of protozoan parasite, intercellular diffusion of intracellularly injected Lucifer Yellow was dramatically reduced. Immunocytochemistry with antibodies specific for connexin43 (in astrocytes) or both connexin43 and connexin26 (for leptomeningeal cells) demonstrated that punctate gap junctional staining was much reduced in infected cells, although uninfected neighbors could display normal connexin abundance and distribution. Western blot analyses revealed that connexin43 abundance in both cell types infected with either parasite was similar to that in uninfected cells. Phosphorylation state of connexin43 (inferred from electrophoretic mobility of connexin43 isoforms) was not significantly affected by the infection process. Immunocytochemistry of whole brains from animals acutely infected with either parasite also showed a marked reduction in connexin43 expression. We conclude that infection of both types of brain cells with either protozoan parasite results in a loss of intercellular communication and organized gap junction plaques without affecting expression levels or posttranslational processing of gap junction proteins. Presumably, these changes in gap junction distribution result from altered targeting of the junctional protein to the plasma membrane, and/or from changes in assembly of subunits into functional channels.     

Global progress in infectious disease control

There is both good news and bad news concerning infectious disease control globally. The good news is that smallpox has been eradicated, eradication of poliomyelitis and guinea worm disease is on track, and many infectious diseases are under effective control in much of the world. The advances are primarily the result of improved sanitation, effective use of vaccines, and introduction and use of specific therapies (whose impact has primarily been on mortality, rather than incidence). The bad news is that infectious diseases are still the leading cause of death world-wide, new diseases are emerging, old diseases are re-emerging, there are ominous interactions between diseases, and antibiotic resistance is emerging as a major problem. There are many promising developments for the future, including new and improved vaccines, new specific therapies, and new strategies to deal with infectious disease. However, unless eradicated, infectious diseases remain a threat and require continuous efforts to be kept under control. Given the ability of infectious agents to evolve, it is certain that the future will also hold new problems and new diseases.     

Alpha-melanocyte stimulating hormone-induced pigmentation is blocked by depletion of protein kinase C

Partial regions of the mRNA encoding a major part of translation elongation factor 2 (EF-2) from a kinetoplastid protozoan, Trypanosoma cruzi, were amplified by means of polymerase chain reaction and their primary structures were analyzed. The deduced amino acid sequence was aligned with those of other eukaryotic and archaebacterial EF-2s, and the phylogenetic relationships among eukaryotes were inferred by the maximum likelihood (ML) method. ML analyses of EF-2 phylogeny using six different stochastic models of amino acid substitutions consistently suggested that the phylogenetic position of T. cruzi is likely to be closer to higher eukaryotes than that inferred from the phylogeny of small subunit ribosomal RNA (SrRNA). These results are consistent with those for the elongation factor 1alpha (EF-1alpha) phylogeny. When the EF-1alpha and EF-2 phylogenies were totally evaluated, it became much clearer that the divergence of T. cruzi occurred later than that of a mitochondrion-lacking protozoan, Entamoeba histolytica, although this is not conclusive.     

Human need and the right of patients to privacy

The 1996 World Health Report highlights the global importance of infectious diseases, especially among young children, and stresses the impact of new or emerging diseases. Neonatal infections are old diseases. What is needed is a new recognition that they are important causes of morbidity and mortality and that simple interventions are available that can make a significant impact on the incidences of infection and death related to infection.     

Toxoplasmosis and immunosuppression

Toxoplasmosis is a widely distributed zooanthroponosis, caused by the ubiquitous obligatory intracellular protozoan parasite Toxoplasma gondii. Once infected, the host acquires lifelong immunity induced by the persistence of the parasite in an encysted form. While T. gondii infection in pregnancy has long been known as a significant cause of perinatal morbidity and mortality (congenital toxoplasmosis), its significance as an opportunistic agent has been increasingly recognized during the last decade, particularly with the outbreak of AIDS. Reactivation of a previously latent infection results in a wide clinical spectrum, predominantly within the central nervous system. The paper reviews recent data on the significance of toxoplasmosis as an opportunistic infection in immunosuppressed individuals, such as patients with malignant and systemic diseases treated with immunosuppressive drugs, organ transplant recipients, and, first and foremost, patients with AIDS. A high prevalence of latent toxoplasmosis in Yugoslavia indicates a high local exposure to infection reactivation. While a definitive diagnosis of toxoplasmosis is difficult in the immunosuppressed, its treatability as opposed to a fatal outcome, if untreated, demands that physicians caring for the above categories of patients keep in mind toxoplasmosis and its possible clinical presentations and include them in the differential diagnosis of these conditions.     

The biogenesis and properties of the parasitophorous vacuoles that harbour Leishmania in murine macrophages

Leishmania are protozoan parasites that, as amastigotes, live in the macrophages of mammalian hosts within compartments called parasitophorous vacuoles. These organelles share features with late endosomes/lysosomes and are also involved in the trafficking of several major histocompatibility complex (MHC)-encoded molecules. Improved knowledge of the parasitophorous vacuoles may help clarify how these protozoa persist in their hosts.     

Germination, growth, and sporulation of Bacillus thuringiensis subsp. israelensis in excreted food vacuoles of the protozoan Tetrahymena pyriformis

Spores of Bacillus thuringiensis subsp. israelensis and their toxic crystals are bioencapsulated in the protozoan Tetrahymena pyriformis, in which the toxin remains stable. Each T. pyriformis cell concentrates the spores and crystals in its food vacuoles, thus delivering them to mosquito larvae, which rapidly die. Vacuoles containing undigested material are later excreted from the cells. The fate of spores and toxin inside the food vacuoles was determined at various times after excretion by phase-contrast and electron microscopy as well as by viable-cell counting. Excreted food vacuoles gradually aggregated, and vegetative growth of B. thuringiensis subsp. israelensis was observed after 7 h as filaments that stemmed from the aggregates. The outgrown cells sporulated between 27 and 42 h. The spore multiplication values in this system are low compared to those obtained in carcasses of B. thuringiensis subsp. israelensis-killed larvae and pupae, but this bioencapsulation represents a new possible mode of B. thuringiensis subsp. israelensis recycling in nontarget organisms.     

Cryptosporidiosis in persons with HIV infection

Cryptosporidium parvum is an ubiquitous protozoan parasite that is a major cause of diarrhoea in individuals infected with human immunodeficiency virus. The hallmarks of infection include profuse watery diarrhoea which may become chronic in the severely immunosuppressed individual. No uniformly effective therapy exists. Current treatment relies upon a trial of anti-retroviral and specific anti-cryptosporidial medications, adequate fluid and nutritional support, and anti-motility agents.     

Future developments in genetic research. I. Technological possibilities

The attention in genetic research is shifting from the determination' of (rare) monogenic disorders to identification of genetic risk factors for important diseases at adult age. Mapping of all man's 80,000-100,000 genes will also provide more insight into the gene polymorphisms and mutations that are associated with various types of cancer, certain cardiovascular diseases, diabetes and neurodegenerative disorders, including Alzheimer dementia. Apart from new diagnostic possibilities, the DNA techniques create new prospects for the study of the pathogenesis of diseases and the devising of new strategies for treatment. Examples are familial hypercholesterolaemia, diabetes, breast cancer and colorectal carcinoma.     

The fungal mitochondrial genome project: evolution of fungal mitochondrial genomes and their gene expression

The goal of the fungal mitochondrial genome project (FMGP) is to sequence complete mitochondrial genomes for a representative sample of the major fungal lineages; to analyze the genome structure, gene content, and conserved sequence elements of these sequences; and to study the evolution of gene expression in fungal mitochondria. By using our new sequence data for evolutionary studies, we were able to construct phylogenetic trees that provide further solid evidence that animals and fungi share a common ancestor to the exclusion of chlorophytes and protists. With a database comprising multiple mitochondrial gene sequences, the level of support for our mitochondrial phylogenies is unprecedented, in comparison to trees inferred with nuclear ribosomal RNA sequences. We also found several new molecular features in the mitochondrial genomes of lower fungi, including: (1) tRNA editing, which is the same type as that found in the mitochondria of the amoeboid protozoan Acanthamoeba castellanii; (2) two novel types of putative mobile DNA elements, one encoding a site-specific endonuclease that confers mobility on the element, and the other constituting a class of highly compact, structured elements; and (3) a large number of introns, which provide insights into intron origins and evolution. Here, we present an overview of these results, and discuss examples of the diversity of structures found in the fungal mitochondrial genome.     

Out on the farm with DNA vaccines

DNA vaccination is a rapidly developing technology that offers new approaches for the prevention of disease. This technology may permit the production of new vaccines against diseases that have no current vaccine, as well as allowing the development of improved vaccines to replace existing products. We describe how DNA vaccination is being developed for use in commercial animal production, with an emphasis on viral diseases, and discuss the existing hurdles to its development and use.     

Protozoan and helminthic infections of the intestines of humans in the inyanga area of Rhodesia

A survey of the protozoan and helminth species which infest the intestines of the people in the lnyanga area of Rhodesia has revealed a wide range of species. Of the protozoa, Entamoeba coli was by far the commonest species encountered (45,8%) and of the helminths, hookworms (8,2%) were the most common.     

Infectious causes of chronic inflammatory diseases and cancer

Powerful diagnostic technology, plus the realization that organisms of otherwise unimpressive virulence can produce slowly progressive chronic disease with a wide spectrum of clinical manifestations and disease outcomes, has resulted in the discovery of new infectious agents and new concepts of infectious diseases. The demonstration that final outcome of infection is as much determined by the genetic background of the patient as by the genetic makeup of the infecting agent is indicating that a number of chronic diseases of unknown etiology are caused by one or more infectious agents. One well-known example is the discovery that stomach ulcers are due to Helicobacter pylori. Mycoplasmas may cause chronic lung disease in newborns and chronic asthma in adults, and Chlamydia pneumoniae, a recently identified common cause of acute respiratory infection, has been associated with atherosclerosis. A number of infectious agents that cause or contribute to neoplastic diseases in humans have been documented in the past 6 years. The association and causal role of infectious agents in chronic inflammatory diseases and cancer have major implications for public health, treatment, and prevention.     

Autoimmune rheumatic diseases associated with HIV infection and its pathogenesis

In autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or initiating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on autoimmune or rheumatic disorders associated with HTLV-I or HIV-I infection as well as new data from the autoimmune rheumatic mouse (MLR/1pr mouse) model might help to answer the questions how and what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in patients with HIV-I infection, apoptosis and molecular mimicry to autoantigens opens new approaches to the study of rheumatic disease pathogenesis.     

Refractive status in children after long-term follow up of cataract surgery with intraocular lens implantation

The Epstein-Barr virus is a ubiquitous human herpesvirus that is associated with an increasing number of human malignancies. Among these are Epstein-Barr virus-associated lymphoproliferative diseases in immunocompromised patients, a spectrum of mainly B-cell diseases that range from polyclonal lymphoproliferative diseases, which resolve when immunosuppression is halted, to highly malignant lymphomas. Progress has identified Epstein-Barr virus gene products involved in B-cell transformation, variation in Epstein-Barr virus transforming genes, distinct target cell populations with differing regulation of Epstein-Barr virus expression, and selective recruitment of other supportive cell types as factors in the heterogeneity of lymphoproliferative diseases. New therapeutic approaches to treat lymphoproliferative diseases are also being developed. Finally, xenotransplantation poses new risks for the introduction of Epstein-Barr virus-like viruses and more aggressive lymphoproliferative diseases in heavily immunosuppressed patients.