Protozoa as a cause of recurrent abdominal pain in children.

OBJECTIVES: The aim of this study was to investigate whether protozoa can be identified as a cause of recurrent abdominal pain (RAP), and whether protozoan infections can be recognized by a specific clinical presentation. METHODS: For 2 years, all patients (ages 4-16 years) fulfilling the Apley criteria of RAP referred to secondary care were prospectively evaluated for protozoa (Giardia lamblia, Dientamoeba fragilis, Blastocystis hominis) and treated if positive. Re-examination followed at least 10 days after treatment. Disappearance of pain with eradication and a pain-free follow-up of at least 6 months were considered to be indicative of a causal relation with RAP. The predictive value of the characteristics of the pain for protozoan infections was calculated. RESULTS: Of 220 included patients (92 boys, mean age 8.8 years), 215 brought a stool sample; 73 (34%) carried parasites, 10 of whom had 2 parasites, 2 had 3 parasites. Sixty-five patients were treated. Twenty-five (11%) were pain-free after eradication (21 had D fragilis, 8 B hominis, 4 G lamblia), of whom 11 had another infection (2) or constipation (9) as second diagnosis for the pain. Five had recurrence of infection with D fragilis and were again pain-free with eradication. Patients with protozoa as cause of their pain did not show differences with respect to their presentation when compared with patients with an asymptomatic infection and patients without protozoa. CONCLUSIONS: Protozoa were found as the cause of pain in 6% to 11% of children with RAP. These patients did not show a characteristic presentation when compared with patients with other causes of abdominal pain.

Parasitic infections in HIV infected individuals: diagnostic & therapeutic challenges.

After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leishmaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection.

Relationships between intestinal parasitosis and handedness.

The aim of the study was to investigate if there is a possible relation between intestinal parasitosis and handedness in patients with suspected intestinal parasitosis. Hand preference was assessed on the Edinburgh Handedness Inventory. Stool samples were examined microscopically for the presence of parasite. In the present study right-handers had many more helminth infections and left-handers had many more protozoon infections. Lower rate of helminth infections in the present study, and higher asthma incidences in the left-handed population in literature, may be associated with different immune machinery in left-handed people than in right-handed ones.

13 Plus 1: A 30-Year Perspective on Microtubule-Based Motility in Dictyostelium.

Individual gene analyses of microtubule-based motor proteins in Dictyosteliumdiscoideum have provided a rough draft of its machinery for cytoplasmic organization and division. This review collates their activities and looks forward to what is next. A comprehensive approach that considers the collective actions of motors, how they balance rates and directions, and how they integrate with the actin cytoskeleton will be necessary for a complete understanding of cellular dynamics.

Elevated levels of urinary hydrogen peroxide, advanced oxidative protein product (AOPP) and malondialdehyde in humans infected with intestinal parasites.

Oxidative stress has been implicated as an important pathogenic factor in the pathophysiology of various life-threatening diseases such as cancer, cardiovascular diseases and diabetes. It occurs when the production of free radicals (generated during aerobic metabolism, inflammation, and infections) overcome the antioxidant defences in the body. Although previous studies have implied that oxidative stress is present in serum of patients with parasitic infection there have been no studies confirming oxidative stress levels in the Malaysian population infected with intestinal parasites. Three biochemical assays namely hydrogen peroxide (H2O2), lipid peroxidation (LP) and advanced oxidative protein product (AOPP) assays were carried out to measure oxidative stress levels in the urine of human subjects whose stools were infected with parasites such as Blastocystis hominis, Ascaris, Trichuris, hookworm and microsporidia. The levels of H2O2, AOPP and LP were significantly higher (P<0.001, P<0.05 and P<0.05 respectively) in the parasite-infected subjects (n=75) compared to the controls (n=95). In conclusion, the study provides evidence that oxidative stress is elevated in humans infected by intestinal parasites. This study may influence future researchers to consider free radical-related pathways to be a target in the interventions of new drugs against parasitic infection and related diseases.

An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites.

In biology, models are experimental systems meant to recreate aspects of diseases or human tissue with the goal of generating inferences and approximations that can contribute to the resolution of specific biological problems. Although there are many models for studying intracellular parasites, their data have produced critical contradictions, especially in immunological assays. Peripheral blood mononuclear cells (PBMCs) represent an attractive tissue source in pharmacogenomics and in molecular and immunologic studies, as these cells are easily collected from patients and can serve as sentinel tissue for monitoring physiological perturbations due to disease. However, these cells are a very sensitive model due to variables such as temperature, type of stimulus and time of collection as part of posterior processes. PBMCs have been used to study Toxoplasma gondii and other apicomplexan parasites. For instance, this model is frequently used in new therapies or vaccines that use peptides or recombinant proteins derived from the parasite. The immune response to T. gondii is highly variable, so it may be necessary to refine this cellular model. This mini review highlights the major approaches in which PBMCs are used as a model of study for T. gondii and other apicomplexan parasites. The variables related to this model have significant implications for data interpretation and conclusions related to host-parasite interaction.

Sickness behaviour pushed too far--the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma.

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines--generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbalpha) that control circadian rhythm--becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases.

Toll-Like receptors (TLRs) and their ligands.

The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by pattern recognition receptors (PRRs), which recognize microbial components that are essential for the survival of the microorganism. PRRs are germline-encoded, nonclonal, and expressed constitutively in the host. Different PRRs react with specific ligands and lead to distinct antipathogen responses. Among them, Toll-like receptors (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa, and viruses, and they play a major role in innate immunity. Here, we review the mechanism of pathogen recognition by TLRs.

Histological and lectin binding changes in the genital tract of mice infected with Tritrichomonas foetus.

An experimental murine model of bovine genital tritrichomonosis is described. Female mice were inoculated per vaginam with Tritrichomonas foetus and a sample of the study population was killed every 3 days up to 60 days post-infection. Microscopical changes in the reproductive organs were assessed and immunohistochemistry was used to detect T. foetus within these tissues. Lectin histochemistry was used to determine changes in the expression of carbohydrates within the reproductive mucosa. A range of microscopical changes were detected in the uterine endometrium by 10 days post-inoculation and these were associated with the presence of the protozoan. The endometrial changes included endometritis and ulceration, mucosal atrophy and glandular metaplasia, and were similar to those reported in naturally infected cows. Changes in lectin binding were recognized first in the vagina where there was increased binding of Ulex europaeus agglutinin-1 (UEA-1) which was maximal on day 16 post-inoculation. Within the uterus, there was increased binding of soy bean agglutinin (SBA) which was maximal on day 19 post-inoculation, and of peanut agglutinin (PNA) which was maximal on day 16 post-inoculation. These changes in carbohydrate expression parallel the infection kinetics, since they appeared first in the vagina and later in the uterus. The changes may reflect either a host reaction against the infection or the production of enzymes by T. foetus, which act to enhance adhesion and colonization of the genital organs by the organism. The kinetics and pathogenesis of this murine infection are similar to those of the natural bovine disease, suggesting that this model system may be valuable for further studies of this disease.

The roles of galectins in parasitic infections.

Galectins is a family of multifunctional lectins. Fifteen galectins have been identified from a variety of cells and tissues of vertebrates and invertebrates. Galectins have been shown to play pivotal roles in host-pathogen interaction such as adhesion of pathogens to host cells and activation of host innate and adaptive immunity. In recent years, the roles of galectins during parasite infections have gained increasing attention. Galectins produced by different hosts can act as pattern recognition receptors detecting conserved pathogen-associated molecular patterns of parasites, while galectins produced by parasites can modulate host responses. This review summarizes some recent studies on the roles of galectins produced by parasitic protozoa, nematodes, and trematodes and their hosts. Understanding the roles of galectins in host-parasite interactions may provide targets for immune intervention and therapies of parasitic infections.

Macrophage nutriprive antimicrobial mechanisms.

In addition to oxidative and antibiotic mechanisms of antimicrobial activity, macrophages are able to deprive intracellular pathogens of required nutrients. Thus, microbial killing may not rely only in the toxic environment the microbe reaches but also may result from the scarcity of nutrients in the cellular compartment it occupies. Here, we analyze evidence for such nutriprive (from the latin privare, to deprive of nutrients), antimicrobial mechanisms. Although the direct analysis of nutrient availability is most often not feasible, indirect evidence of lack of nutrients in the microbial organelles has been inferred from the study of mutants, the analysis of gene expression, and the consequences of changing the intracellular location of the pathogen. We propose that according to the microbe and its survival strategy, different mechanisms to impede access to nutrients may be constitutively present or may be induced by cytokines and other pathways. Thus, membrane transporters may remove nutrients from vacuolar compartments, and enzymes may degrade some growth factors. A series of diverse compounds may sequester other molecules required for microbial growth, as exemplified by the action of iron chelators. Modulation of vesicular trafficking may prevent the fusion of certain vesicles containing nutrients with those containing the pathogen, counteracting the evasion strategies of the pathogen. The understanding of these mechanisms will certainly help in designing new therapeutic and prophylactic approaches to preventing infectious diseases.

Mitigation of lethal effects of Karlodinium veneficum and K. armiger on Sparus aurata: changes in haematocrit and plasma osmolality.

Between January and April 2000, several experiments were performed during a Karlodinium spp. proliferation in Alfacs Bay (Ebro delta, NW Mediterranean) to determine the effects of these dinoflagellates on sea bream Sparus aurata cultivated in the area. Moribund fish showed an increase in plasma osmolality together with a decrease in the haematocrit percentage compared to control fish. The efficacy of copper sulphate, hydrogen peroxide, potassium permanganate and formalin against Karlodinium spp. was also tested. None of these treatments had mitigation effects when applied in the presence of fish; on the contrary, lethal effects appeared at lower Karlodinium spp. densities compared to fish control groups. When a lytic agent, such as copper sulphate, was used as a water pre-treatment, in the absence of fish, Karlodinium spp. toxicity was significantly reduced. Protocols for water pre-treatments were studied as a potential tool for combating Karlodinium spp. in fish farms.

Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey.

BACKGROUND: As traditional lifestyle and diets change with social and economic development, disadvantaged communities in low- and middle-income countries increasingly face a double burden of communicable and non-communicable diseases. We studied the relationship between physical fitness and infections with soil-transmitted helminths (STHs), intestinal protozoa and Helicobacter pylori among schoolchildren in Port Elizabeth, South Africa. METHODS: We conducted a cross-sectional survey among 1009 children, aged 9 to 12 years, from eight primary schools in socioeconomically disadvantaged neighbourhoods of Port Elizabeth. Physical fitness was determined using field-deployable tests of the Eurofit fitness test battery. Stool samples were analysed with the Kato-Katz thick smear technique to diagnose STHs and with rapid diagnostic tests (RDTs) to detect intestinal protozoa and H. pylori infections. Haemoglobin (Hb) levels were assessed and anthropometric indicators determined. RESULTS: Complete data were available for 934 children (92 %). In two schools, high STH prevalences were found (Ascaris lumbricoides 60 and 72 %; Trichuris trichiura 65 % each). For boys and girls co-infected with A. lumbricoides and T. trichiura (n = 155) the maximal oxygen uptake (VO2 max) was estimated to be 50.1 and 47.2 ml kg(-1) min(-1), compared to 51.5 and 47.4 ml kg(-1) min(-1) for their non-infected peers (n = 278), respectively. On average, children without helminth infections had greater body mass (P = 0.011), height (P = 0.009) and a higher body mass index (P = 0.024) and were less often stunted (P = 0.006), but not significantly less wasted compared to their peers with a single or dual species infection. Among 9-year-old boys, a negative correlation between helminth infections and VO2 max, grip strength and standing broad jump distance was observed (P = 0.038). The overall mean Hb level was 122.2 g l(-1). In the two schools with the highest prevalence of STHs the Hb means were 119.7 and 120.5 g l(-1), respectively. CONCLUSIONS: Intestinal parasite infections appear to have a small but significant negative effect on the physical fitness of infected children, as expressed by their maximal oxygen uptake. We observed a clear impact on anthropometric indicators.

Tick-borne bacterial, rickettsial, spirochetal, and protozoal infectious diseases in the United States: a comprehensive review.

Approximately 900 tick species exist worldwide, and they parasitize a variety of mammals, including humans; thus, ticks play a significant role in the transmission of infectious diseases. In the United States, tick-borne diseases are seasonally and geographically distributed; they typically occur during spring and summer but can occur throughout the year. Tick-borne diseases are endemic to a variety of geographic regions of the United States, depending on the species of tick commonly found in a specific locale. Specific tick-borne diseases are difficult to diagnose. Most patients have vague constitutional symptoms and nonspecific laboratory findings. Initially, serologic methods are of little benefit because they lack sensitivity early in the disease course. Therefore, a thorough history and physical examination are necessary for establishing a diagnosis. Antimicrobial regimens for tick-borne infections are poorly studied but well established. Tetracyclines and rifampin form the cornerstones of therapy for most tick-borne infections, but these agents may not be suitable for all patient populations. Therefore, no single agent can be chosen empirically to treat all tick-borne diseases. Because pharmacists are the most accessible health care providers, they are often asked how to treat tick-borne diseases. Thus, practitioners should be familiar with the ticks that inhabit their locale.

Oxidative stress and antioxidant defenses: a target for the treatment of diseases caused by parasitic protozoa.

Parasitic protozoa cause several diseases, affecting hundreds of millions, particularly in underdeveloped countries. Although these organisms are eukaryotic cells, some of them present major differences with their mammalian host in selected metabolic pathways. These differences may be exploited as targets for developing better pharmacological agents for the treatment of specific parasitic diseases. This review describes some of the differences in terms of antioxidant defenses between these organisms and their mammalian host, which may provide useful targets for the treatment of these diseases. Some of the potential targets are: (i). iron metabolism in Plasmodium, (ii). the presence of a Fe-containing form of superoxide dismutase in trypanosomatids and malaria-causing parasites, (iii). the unique trypanothione-dependent antioxidant metabolism in trypanosomatids, (iv). the ascorbate peroxidase found in Trypanosoma cruzi and perhaps present in other trypanosomatids.

Adaptive physiological processes in the host during gastrointestinal parasitism.

Parasite infection of the gastrointestinal tract with helminths or protozoa induces detrimental effects on host tissues and host physiology, which have been extensively studied and reviewed. However, parasitism of the digestive system is also associated with adaptive, compensatory phenomena based on changes in host physiology or structures and which tend to counterbalance the negative consequences. The objective of this review is to describe these adaptive processes and their possible underlying mechanisms. Different processes which tend to attenuate the effect of either the loss of appetite, the intestinal malabsorption or the increased tissue losses have been assessed. These processes have been reported both for helminth and protozoan infections, where they present similar characteristics. The mechanisms involved in the adaptation to parasitism remain largely unidentified. The role of feedback mechanisms based on host regulation, possibly through gastrointestinal hormones, has been raised. On the other hand, some data support the proposal that parasites themselves may initiate some of the adaptive processes and consequently favour their own survival. These adaptive phenomena appear to be an essential component in the dynamic balance between host and parasites. Also, parasite infections represent unique models to study the adaptation of the gastrointestinal tract to aggressors.

Aspects of the ecology of metazoan ectoparasites of marine fishes.

Numerous (3947) individuals of 102 marine fish species from Papua New Guinea, New Zealand, the North Sea, Antarctica, the deepsea and coast of southeastern Australia, Pacific Canada, Brazil, Argentina and the Great Barrier Reef were examined for metazoan ectoparasites. Of the 102 fish species, 86 harboured at least 1 parasite species, and only in Antarctica and the deepsea were large proportions of fish species found to be free of ectoparasites. The mean prevalence of infection was 30.1%, the average of abundances was 6.7 parasites per fish, due to very heavy intensities of some parasite species (mean median abundance 4.31). Most parasite species exhibited a clustered distribution in the host populations, as measured by variance to mean ratios, i.e. some fish were more, and others less, heavily infected than if infection were random. Core and satellite species cannot be distinguished unambiguously, because numbers of parasites on almost all hosts are too small for any bimodality to become apparent. On average, the most dominant species represented 90% of all parasite individuals of a particular fish; different parasite species were often dominant on different fish individuals of a particular host species. Both abundances and maximum intensities of infection were positively correlated with prevalence of infection. Community richness varies greatly at and between localities, with the lowest richness found in Antarctic and deepsea fish and the highest richness in tropical fish. Species richness, abundance and prevalence of infection in many fish groups (with different ecological characteristics) are strongly correlated with temperature. If fish from all localities were pooled, pelagic fish had fewer intensities and (jointly with benthopelagic fishes) fewer species than benthic fish, and planktivorous fish had lower abundances and prevalences of infection than predatory and omnivorous fish. Prevalences of infection, abundance and parasite species richness were significantly correlated with host length. Fifteen positive and 1 negative associations among species were found. This and the generally low prevalences and abundances of infection indicate that competitive interactions are probably scarce. Overall, the findings indicate that most (if not all) metazoan ectoparasite communities of marine fish live in non-saturated, little-ordered assemblages.

Current topics in protozoal diseases.

The author reviews seven protozoal diseases, emphasizing the current development but also briefly reviewing the basic knowledge in epidemiology, parasitology, clinical features, pathology, and laboratory diagnosis. Cryptosporidiosis, microsporidiosis, and cyclosporiasis, which are newly discovered diseases in humans, and pneumocystosis, toxoplasmosis, and isosporiasis, which are important opportunistic infections in patients with acquired immunodeficiency syndrome, are discussed. The author also presents acanthamoeba keratitis, a disease seen mainly in contact lens wearers that is expected to have a higher prevalence in the near future.