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Vitamin A and immunity to viral, bacterial and protozoan infections.

Studies in animal models and cell lines show that vitamin A and related retinoids play a major role in immunity, including expression of mucins and keratins, lymphopoiesis, apoptosis, cytokine expression, production of antibody, and the function of neutrophils, natural killer cells, monocytes or macrophages, T lymphocytes and B lymphocytes. Recent clinical trials suggest that vitamin A supplementation reduces morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection and malaria. Immune responses vary considerably during different infections, and the available data suggest that the modulation of immune function by vitamin A may also vary widely, depending on the type of infection and immune responses involved.

Bacterial Infections↗

[Protozoan Infection Of The Domestic Animals And Poultry In Korea]

Researches in veterinary protozoology until the end of World War II were carried out entirely by Japanese workers such as Danagga, Yamada, Yuhoba and Isshiki. After the Korean war, investigations have been made by several Korean researchers such as Lee's, Son, Joen and Jang. The total species and genera of veterinary protozoa reported by authors up to date were 19 genera and 59 species except the commensal ciliates. Incidence of the protozoa were carried out for 4 years(1972-l975) by examining fecal samples and vaginal swabs in order to know the parasitic status of the domestic animals and poultry.

Journal Article↗

[Epidemiological Studies On Protozoan Infection In Gyeong-Gi Do And Jeonra Bug Do]

The present study was designed to elucidate the recent prevalence of the intestinal protozoa and to demonstrate the relationship on prevalence of the surveyed population with their academic career and living conditions. During the period from May to July 1981, total 2,735 fecal specimens were collected from the inhabitants of 11 areas in Gyeong-gi Do (province) near by Seoul City, and 6 areas in Jeonra Bug Do, southwestern part of Korea. The samples were fixed with SAF solution and were examined by formalin-ether sedimentation technique. The results are summarized as follows: Overall positive rate of intestinal protozoa was 11.1 %: Gyeong-gi Do, 10.7 %; Jeonra Bug Do, 11.7 %. Five species of intestinal protozoa were detected: Entamoeba histolytica 0.69 %, Entamoeba coli 5.52 percent, Endolimax nana 2.71 %, Giardia lamblia 2.23 %, Iodamoeba butschlii 0.l8 %. Highest positive rates among the examined areas were recognized: Incheon City of Gyeong-gi Do, 26.7 %; Im-sil Gun(county) of Jeonra Bug Do, 19.9 %. By species, E. nana showed the highest prevalence rate (13.74 %) in Incheon City, and E. histolytica (2.37 %) and E. coli (9.95 %) in Im-sil Gun. Prevalence of E. histolytica in rural areas was higher than in urban areas. No significant difference in the prevalence rate by sex and age was recognized, although the group under 10 years and over 60 years were lower than in other age groups. The highest positive rate of E. histolytica was observed in pauper group and significant linearity of prevalence rate of E. histolytica by monthly income was observed. The inhabitants who used conventional latrine showed higher prevalence, 11.5 %, than the group of inhabitants who used modified privy. Although no significant difference of positive rate was recognized by academic career, but the lowest prevalence rate was observed in college graduates. Over half of the surveyed population, 64.8 % has no experience on anthelmintic practice. Number of anthelmintic application resulted no difference in prevalence. In conclusion, prevalences of intestinal protozoa in Gyeong-gi Do and Jeonra Bug Do decreased remarkably in comparison with those of one decade before. However, economic level, academic career and anthelmintic administration seemed no essential reasons for such declination.

Journal Article↗

Changes in C3 metabolism during protozoan infection (Babesia rodhaini) in rats.

Metabolism of the third component of complement (C3) and IgG was measured in rats before and during infection with the hemosporidium agent Babesia rodhaina. In the course of infection, hypocomplementemia and immune complex nephritis developed. During babesial infection, in most animals the half-life of C3 fell sharply, as did serum levels of C3; the catabolic rate for C3 sharply increased, whereas the synthetic rate sharply decreased. In contrast, the catabolic rate for IgG remained unchanged. The alteration in the metabolism of C3 in the face of nonparallel changes in IgG metabolism suggests that abnormal glomerular filtration and increased vasopermeability cannot explain the findings. Babesial infection in the rat provides a useful model for the study of acquired C3 metabolic defects that have been observed in humans with immune complex diseases.

Animals↗

[Highly Active AntiRetroviral Therapy and opportunistic protozoan infections].

Opportunistic parasite infections (OPIs) are an important cause of morbidity and mortality in persons infected with HIV. In industrialised countries, the use of Highly Active AntiRetroviral Therapy (HAART) results to be effective in suppressing the HIV viral load, with a quantitative and qualitative improvement in the CD4+ T-cell count followed by a strong reduction of opportunistic infections including those caused by parasites. These successes have been mainly attributed to the reconstitution of the cell immunity, which play the most important role in controlling OPIs. However, there are many clinical reports and several laboratory results, which suggest that the control of OPIs in HIV-positive persons under HAART is also induced by the anti-HIV protease inhibitors (PIs), which inhibit the aspartyl proteases of the parasites. The non-conventional use of HIV-PIs seems to be an alternative way for the treatment of parasitic infections, which should be deeply investigated. Of five longitudinal studies carried out before and after the introduction of HAART, four studies showed a strong reduction of toxoplasmic encephalitis (TE) in HIV-positive persons under HAART, whereas in another study, no difference was observed in the incidence rate of TE before and after the introduction of HAART. The influence of HAART in reducing TE has been also confirmed in a randomised, controlled clinical trial, which showed that there is no increase in the risk of developing TE after beginning HAART, even though HIV-infected persons with TE had a discontinuing prophylaxis for Toxoplasma gondii. Four HIV protease inhibitors were tested against the T. gondii virulent RH strain in vitro, alone or in association with pyrimethamine or sulfadiazine. Ritonavir and nelfinavir were highly inhibitory for the parasite growth. Furthermore, none of the antiviral drugs negatively affected the anti-Toxoplasma activity of pyrimethamine or sulfadiazine. In HIV-Leishmania co-infections, a changing pattern has been observed in the HAART era, characterised by a high rate of relapses, which could be explained by the increased survival rate resulting from the effective antiretroviral therapy. A 64.8% decrease of the visceral leishmaniasis incidence was detected after HAART began to be used extensively in Spain. In a large cohort study carried out in ten European countries and in Australia, the relative risk to contract cryptosporidiosis as the first AIDS defining disease was reduced by 96% in the HAART era. In Italy, the relative risk of death for cryptosporidiosis reduced of 74% in the period 1997-98, when HIV-positive persons received HAART. In a large study carried out in Italy, isosporiasis was included in the group of opportunistic infections, of which the relative hazards showed a reduction of 95% in the HAART era. Since 1997, there was the evidence that the use of HAART in persons with advanced HIV infection can improve chronic diarrhoea and lead to disappearance of Enterocytozoon bieneusi from the stools. Although the reconstitution of the cellular immunity seems to be the main factor influencing the reduction of OPIs in persons with AIDS who undergo HAART, there are clinical and microbiological evidences, as well as in vitro and in vivo results, which indicate direct effects of HIV-PIs on the proteases of opportunistic parasites. These findings stress the existence of non-conventional unexpected benefits of PIs in HAART against protozoa. In addition, this benefit of PIs has been demonstrated also for Candida albicans secreted aspartyl proteases and for P. carinii acid proteases. In spite of these important results, HIV PIs are still very toxic for humans, specially in cases of very long treatment, and no clinical trial has been carried out for persons at risk, such as children and pregnant women, because the priority was to reduce the severity of HIV and not the evaluation of possible side effects of the therapy. It follows that further researches are needed to establish the non-conventional use of HIV PIs. Furthermore, the study of PIs against specific aspartyl proteases of those opportunistic protozoa that cause severe and intractable diseases, could be considered an alternative way towards the development of new drugs that may prove effective against these infections.

AIDS-Related Opportunistic Infections↗

Cryptosporidiosis and other intestinal protozoan infections in children less than one year of age in Mexico City.

Parasitic diseases are very important in Mexico because of their economic impact and adverse effects on normal growth in children. Cryptosporidiosis has been associated with acute diarrhea in immune competent and incompetent human hosts, fecal contamination of drinking water sources, and handling of animals. Due to the lack of reports on cryptosporidiosis in Mexico, we conducted a parasitologic study in children with diarrhea and other clinical symptoms. The main objectives were 1) to determine the prevalence of cryptosporidiosis in children less than one year of age in Mexico City, and 2) to correlate Cryptosporidium infection with gastrointestinal symptoms. Two hundred fecal samples from children seen at the Gabriel Mancera Familiar Medicine Unit of the Instituto Mexicano del Seguro Social were studied. Children were divided into two groups. Group A was composed of sick children with 6-8 watery diarrheic episodes every 24 hours attended at the emergency service. Group B was composed of healthy babies getting routine check ups. Only children in group A were found to be infected with intestinal protozoa (50% with Giardia lamblia, 41% with Cryptosporidium spp., and 4% with Entamoeba histolytica). The results suggested a high incidence of Cyrptosporidium infections in children in Mexico City, which make these observations useful for future studies.

Animals↗

[Protozoan infection (Blastocystis hominis) concomitant with Pseudomonas sp. peritonitis in continuous ambulatory peritoneal dialysis (CAPD)].

Case-report of protozoal infection (Blastocystis bominis) during Pseudomonas peritonitis in male patient with intestinal diverticulosis on continuous ambulatory peritoneal dialysis (CAPD) treatment for chronic renal failure (CRF). Microscopic morphology and cultural characteristics are summarized from current literature. Photographic images in phase contrast from fresh-observation of faeces and peritoneal fluid are reported. Although other Protozoa (e.g. Acanthamoeba free-living) have already been found in dialysis fluid, this is the first case, referred in literature, of Blastocystis bominis infection in CAPD patients. Some pathogenetic hypothesis are done involving Blastocystis bominis in peritoneal infection, especially in immunodepressed patients like dialysed ones. Although many chemotherapeutics are provided for this protozoiasis during enteritis, in our case no supplement was required except specific antibiotic therapy for Pseudomonas infection. Symbion or pathogen? Is now-a-day the question which troubles parasitologists. Systemic research of Protozoa in dialysed patients is anyhow advisable.

Animals↗

Use of nitazoxanide for gastrointestinal tract infections: treatment of protozoan parasitic infection and beyond.

The United States Food and Drug Administration has approved the parasiticidal agent nitazoxanide for treatment of diarrhea caused by Giardia lamblia/intestinalis or Cryptosporidium parvum. This novel agent has a broad spectrum of activity against many other gastrointestinal pathogens, including bacteria, roundworms, flatworms, and flukes. Nitazoxanide is used in many areas of the world, especially in Central and South America, as a broad-spectrum parasiticidal agent in adults and children. Nitazoxanide appears to be well tolerated, has a relatively low incidence of adverse effect, and displays no significant known drug-to-drug interactions. Recently, preliminary reports indicate that nitazoxanide may be an effective treatment for Clostridium difficile-associated diarrhea as well. Future work will likely solidify and further expand the role of nitazoxanide in the treatment of a wide range of intestinal pathogens.

Journal Article↗

Liposomal vaccines.

Liposomes have been used therapeutically to deliver drugs to certain anatomical sites. The use of liposomes to deliver antigens, although not a new concept, has received less attention. At least two vaccines of nearly identical liposome base composition to our vaccines have been tested in humans. A malaria vaccine study showed that the liposomal preparation is quite safe: reaction profiles of volunteers receiving the vaccine demonstrated little reactivity and virtually no pyrogenicity (14). The concentration of MPLA in the vaccine was substantially higher (nearly 50,000 times) than the pyrogenic dose of free lipid A. The same vaccine, but different antigen (gp120, an HIV protein), was tested in volunteers and had the same lack of toxicity (27). In both studies, antibodies and cytotoxic cells specific for the respective antigens were produced. We have several subunit vaccines under development for infectious diseases (gram negative sepsis, fungal infections, protozoan infections), metabolic disorders (hypercholesterolemia, diabetic retinopathy, macular degeneration), and neoplastic diseases (multi-drug resistant cancer, primary and metastatic tumors, and angiogenic hyperproliferative disorders). In each case, one or more antigens were identified that might be useful in immunologic control of biologic proliferation (i.e., pathogen or tumor growth, rise in serum cholesterol, growth of blood vessels). We anticipate that at least one of these vaccines will be ready for testing in humans in the next calendar year.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Mucosal defences against orally acquired protozoan parasites, emphasis on Toxoplasma gondii infections.

Protozoan parasites that gain access to the host through the mucosal tissue of the alimentary tract may influence the development of intestinal inflammatory disorders. Despite the diversity of the extracellular and intracellular protozoan pathogens discussed in this review, our current understanding of the mechanisms involved in the immune response indicates that a common exuberant immune response to rid the host of these agents is elicited. This robust inflammatory response is orchestrated both by cells from parenchymatous origin such as intestinal epithelial cells and by cells from the haematopoietic system such as macrophages, dendritic cells and lymphocytes. This inflammatory immune response is controlled by a series of regulatory mechanisms in most species. When this balance is no longer evident, an inflammation of the intestine may occur, leading to acute gastritis and diarrhoea and that would add pathological effects to those because of the pathogen itself.

Animals↗

Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii Dopamine, a missing link between schizophrenia and toxoplasmosis?

Toxoplasma gondii, a parasitic protozoan, infects about 30-60% of people worldwide. The latent toxoplasmosis, i.e. life-long presence of cysts in the brain and muscular tissues, has no effect on human health. However, infected subjects score worse in psychomotor performance tests and have different personality profiles than Toxoplasma-negative subjects. The mechanism of this effect is unknown; however, it is supposed that presence of parasites' cysts in the brain induces an increase of the concentration of dopamine. Here we search for the existence of differences in personality profile between Toxoplasma-positive and Toxoplasma-negative subjects by testing 857 military conscripts using a modern psychobiological questionnaire, namely with Cloninger's Temperament and Character Inventory (TCI). ANCOVA showed that Toxoplasma-positive subjects had lower Novelty seeking (NS) scores (P=0.035) and lower scores for three of its four subscales, namely Impulsiveness (P=0.049), Extravagance (P=0.056) and Disorderliness (P=0.006) than the Toxoplasma-negative subjects. Differences between Toxoplasma-negative and positive subjects in NS was inversely correlated with duration of toxoplasmosis estimated on the basis of concentration anti-Toxoplasma antibodies (P=0.031). Unexpectedly, the infected subjects had also lower IQ (P(2)=0.003) and lower probability of achieving a higher education (P(2)<0.0000). Decrease of NS suggests that the increase of dopamine in brain of infected subjects can represent a missing link between toxoplasmosis and schizophrenia.

Adult↗