Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS) of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.

The role of spleen macrophages in malaria: an ultrastructural study

An electronmicroscopy study of the spleen from mice infected with Plasmodium berghei was carried out to investigate the types ofcells in volved in the removal of parasites from the blood, and the mechanisms by which this occurs. Macrophages, particularly from the red pulp and the marginal zone of the spleen, constituted the most important population of phagocytic cells in the spleen. At the height ofparasitaemia, macrophages in the periphery of the white pulp, especially in the mantle zone of secondary follicles, were also found to participate in phagocytosis, although to a limited extent. Our fingings suggest that phagocytosis of free parasites or parasitized erythrocytes in the spleen is an important mechanism of clearance of parasites from the circulation. Parasites removed from the erythrocytes when these cells cross the interendothelial slits are further phagocytosed by neighbouring macrophages. Evidence is presented suggesting that spleen macrophages may act against the parasite through a process of cytotoxicity.

Human mucocutaneous leishmaniasis in Três Braços, Bahia - Brazil: an area of Leishmania braziliensis braziliensis transmission. I. Laboratory diagnosis

Leishmanial parasites were detected in 71.2% of patients with cutaneous disease and 48% of patients with mucosal disease, using principally scanning of imprints mears and histological sections and hamster inoculation. Parasites were more frequent in early cutaneous lesions (p < 0.005) o fless than two month duration. Also they were more common in multiple than single mucosal lesions (p < 0.02) in spite of considerable prior glucan time therapy in the former group. 93% of cutaneous lesions had a positive leishmanin skin test and most of the negatives occurred in patients with lesions of less than one month duration. 97% of patients with single mucosal lesion and 79% with multiple mucosal lesions had a positive skin test. 86% of cutaneous disease and 90% of mucosal disease was associated with a positive indirect immunofluorescent antibody test at a ≥ 1/20 dilution. In both groups multiple lesions were associated with higher titres and titres were significantly higher in patients with mucosal disease compared with cutaneous disease (p < 0.01).

Human immune responses during schistosomiasis mansoni

Studies of immune responses as they occur in patients with schistosomiasis appear to progress relative to corrent technological advances, and to advance despite the understandable inability to pursue in vivo manipulations in this host/parasite system. Emphasis is most often placed on making immunological comparisons between such patient groups as reinfected/non-reinfected, intestinals/hepatosplenic, high/low intensities of infection, infected/uninfected within endemic areas, and those born of infected/uninfected mothers. Based on these types of comparisons, reasonable conjectures can be made regarding the immunological occurrences during this chronic exposure condition. Some consideration is now being given to the immune mechanisms of some of the observations made, and while some of these must then be carried back to experimental models for further manipulation-based analysis, new technological developments continue to assist in the field/bench ability to ask questions that might assist our understanding to a point where this knowledge can be applied to shaping developmental approaches to vaccine development and the goal of alleviating morbidity.

The FML (Fucose Mannose Ligand) of Leishmania donovani: a new tool in diagnosis, prognosis, transfusional control and vaccination against human kala-azar

The Fucose-Mannose Ligand (FML) of Leishmania donovani is a complex glycoproteic fraction. Its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil. The FML-ELISA test, showed 100% sensitivity and 96% specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. More than 20% apparently healthy subjects with positive reaction to FML developed overt kala-azar during the following 10 months. In the screening of human blood donnors, a prevalence of 5% of sororeactive subjects was detected, attaining 17% in a single day. The GP36 glycoprotein of FHL is specifically reconized by human kala-azar sera. The immunoprotective effect of FML on experimental L. donovanii infection was tested in swiss albino mice. The protection scheemes included three weekly doses of FML, supplemented or not with saponin by the subcutaneous or intraperitoneal routes and challenge with 2x 10(7) amastigotes of Leishmania donovani. An enhancement of 80.0 % in antibody response (p<0.001) and reduction of 85.5 % parasite liver burden (p<0.001) was detected in animals immunized with FML saponin, unrespectivety of the immunization route.

Serological and parasitological study and report of the first case of human babesiosis in Colombia

A study on the presence of Babesia in humans was performed in Puerto Berrío (Latitude 6.50deg. Longitude: -74.38deg. River: Magdalena. Area: 74.410km², Colombia-South America). Indirect immunofluorescence, thin and thick blood smears were used to study 194 individuals. Patients were grouped according to their risk-factors for Babesia infection: (group 1) individuals with fever, chills, sweating and other malaria-type symptoms; (group 2) symptomatic and asymptomatic individuals from local cattle ranches, which were enrolled in an active form, and (group 3) workers from the local slaughterhouse. Seven individuals were serologically positive for Babesia: Three individuals presented IgM antibodies against B. bovis, while one had IgG against this species; one individual had IgM against B. bigemina, another had IgG and a third both IgM and IgG against this species. Only one individual was parasitologically positive for Babesiaand serologically positive for Babesia bovis (IgM 1:64)

Concurrent dengue and malaria in the Amazon region

INTRODUCTION: The Amazon region has extensive forested areas and natural ecosystems, providing favorable conditions for the existence of innumerous arboviruses. Over 200 arboviruses have been isolated in Brazil and about 40 are associated with human disease. Four out of 40 are considered to be of public health importance in Brazil: Dengue viruses (1-4), Oropouche, Mayaro and Yellow Fever. Along with these viruses, about 98% of the malaria cases are restricted to the Legal Amazon region. METHODS: This study aimed to investigate the presence of arboviruses in 111 clinical serum samples from patients living in Novo Repartimento (Pará), Plácido de Castro (Acre), Porto Velho (Rondônia) and Oiapoque (Amapá). The viral RNA was extracted and RT-PCR was performed followed by a Multiplex-Nested-PCR, using Flavivirus, Alphavirus and Orthobunyavirus generic and species-specific primers. RESULTS: Dengue virus serotype 2 was detected in two patients living in Novo Repartimento (Pará) that also presented active Plasmodium vivax infection. CONCLUSIONS: Despite scant data, this situation is likely to occur more frequently than detected in the Amazon region. Finally, it is important to remember that both diseases have similar clinical findings, thus the diagnosis could be made concomitantly for dengue and malaria in patients living or returning from areas where both diseases are endemic or during dengue outbreaks.

Use of Poisson spatiotemporal regression models for the Brazilian Amazon Forest: malaria count data

INTRODUCTION: Malaria is a serious problem in the Brazilian Amazon region, and the detection of possible risk factors could be of great interest for public health authorities. The objective of this article was to investigate the association between environmental variables and the yearly registers of malaria in the Amazon region using Bayesian spatiotemporal methods. METHODS: We used Poisson spatiotemporal regression models to analyze the Brazilian Amazon forest malaria count for the period from 1999 to 2008. In this study, we included some covariates that could be important in the yearly prediction of malaria, such as deforestation rate. We obtained the inferences using a Bayesian approach and Markov Chain Monte Carlo (MCMC) methods to simulate samples for the joint posterior distribution of interest. The discrimination of different models was also discussed. RESULTS: The model proposed here suggests that deforestation rate, the number of inhabitants per km², and the human development index (HDI) are important in the prediction of malaria cases. CONCLUSIONS: It is possible to conclude that human development, population growth, deforestation, and their associated ecological alterations are conducive to increasing malaria risk. We conclude that the use of Poisson regression models that capture the spatial and temporal effects under the Bayesian paradigm is a good strategy for modeling malaria counts.

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

INTRODUCTION: The innate immune response is the first mechanism of protection against Trypanosoma cruzi, and the interaction of inflammatory cells with parasite molecules may activate this response and modulate the adaptive immune system. This study aimed to analyze the levels of cytokines and chemokines synthesized by the whole blood cells (WBC) and peripheral blood mononuclear cells (PBMC) of individuals seronegative for Chagas disease after interaction with live T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-α, TGF-β, CCL-5, CCL-2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC, even after incubation with live trypomastigotes. Production of TNF-α by both PBMC and WBC was significantly higher after stimulation with trypomastigotes. Only PBMC produced significantly higher levels of IL-12 after parasite stimulation. Stimulation of cultures with trypomastigotes induced an increase of CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T. cruzi may induce the production of cytokines and chemokines by cells of the innate immune system through the activation of specific receptors not evaluated in this experiment. The ability to induce IL-12 and TNF-α contributes to shift the adaptive response towards a Th1 profile.

Involvement and interactions of different immune cells and their cytokines in human visceral leishmaniasis

Visceral leishmaniasis (VL) or kala-azar, a disseminated infection of the lymphoreticular system of the body, is marked by severe defect in immune system of the host. Successful cure of VL depends on the immune status of the host in combination with the effects of the antileishmanial drugs. The rationale approach towards eradication of this disease would be to potentiate the immune functioning of the host in addition to parasite killing. This review deals with different aspects of adaptive and innate immune responses and explores their role in protection or pathogenesis of VL. IL-10 has emerged as the principal cytokine responsible for disease pathogenesis, although evidences regarding its source during active VL remain inconclusive. On the other hand, IFNγ, under the influence of IL-12, is mostly correlated with healing of the disease. Chemokines are important in mounting cell-mediated immune response as they can prevent parasite invasion in association with cytokines. Different types of T cells like CD4, CD8 and NK T cells also contribute to the immunology of this disease. In spite of conflicting reports, the role of regulatory T cells in VL pathogenesis is important. Recently discovered Th17 subset and its different members have been reported to perform diverse functions in the course of VL and leishmaniasis as a whole. Innate immune responses, depending on the cell types, are essential in early parasite detection and subsequent development of an efficient NK cell response. Immunotherapy targeting IL-10 could be looked upon as an interesting option for the treatment of VL.

The changing distribution of malaria in the Brazilian Amazon, 2003-2004 and 2008-2009

Introduction More than half of the malaria cases reported in the Americas are from the Brazilian Amazon region. While malaria is considered endemic in this region, its geographical distribution is extremely heterogeneous. Therefore, it is important to investigate the distribution of malaria and to determine regions whereby action might be necessary. Methods Changes in malaria indicators in all municipalities of the Brazilian Amazon between 2003-2004 and 2008-2009 were studied. The malaria indicators included the absolute number of malaria cases and deaths, the bi-annual parasite incidence (BPI), BPI ratios and differences, a Lorenz curve and Gini coefficients. Results During the study period, mortality from malaria remained low (0.02% deaths/case), the percent of municipalities that became malaria-free increased from 15.6% to 31.7%, and the Gini coefficient increased from 82% to 87%. In 2003, 10% of the municipalities with the highest BPI accumulated 67% of all malaria cases, compared with 2009, when 10% of the municipalities (with the highest BPI) had 80% of the malaria cases. Conclusions This study described an overall decrease in malaria transmission in the Brazilian Amazon region. As expected, an increased heterogeneity of malaria indicators was found, which reinforces the notion that a single strategy may not bring about uniformly good outcomes. The geographic clustering of municipalities identified as problem areas might help to define better intervention methods.

Spatial analysis of visceral leishmaniasis in the municipality of Rondonópolis, in the Brazilian State of Mato Grosso, from 2003 to 2012: human, canine and vector distribution in areas of disease transmission

INTRODUCTION: Visceral leishmaniasis (VL) is a zoonosis of great importance to public health and is considered a neglected disease by the World Health Organization. The disease has expanded and become more prevalent in urban areas in Brazil. METHODS: Geospatial analyses were performed and thematic maps of the triad of the disease were produced for the study period (2003-2012) in the urban area of the municipality of Rondonópolis in the midwestern State of Mato Grosso (MT), Brazil, TerraView 4.2.2 software was used for the analyses. RESULTS: A total of 87.9% of the 186 confirmed human cases of VL were cured. Children between the ages of 1 and 4 were the most affected. Registered deaths were predominant among adults aged 60 years or older. The urban area of the municipality consists of eight strata and 12 census districts include 237 neighborhoods. All sectors had confirmed cases of VL. During the study period, human cases of the disease were recorded in 90 neighborhoods. The 23 deaths from the disease were distributed in 21 neighborhoods. Sandflies carrying the parasite were captured in 192 out of 200 neighborhoods evaluated for the presence of the VL vector. The presence of dogs carrying the parasite was confirmed in, 140 out of 154 surveyed neighborhoods. CONCLUSIONS: The data demonstrated the endemic nature of VL, with a high percentage of infected children, a high distribution of canine infection, and a wide adaptation and dispersal of the vectors in the urban environment. These results, illustrate the process of urbanization of VL in the municipality of Rondonópolis, MT, Brazil.

Detection of immunogenic proteins from Anopheles sundaicussalivary glands in the human serum

AbstractINTRODUCTION:The saliva of mosquitoes has an important role in the transmission of several diseases, including malaria, and contains substances with vasomodulating and immunomodulating effects to counteract the host physiological mechanisms and enhance pathogen transmission. As immunomodulatory components, salivary gland proteins can induce the generation of specific IgG antibodies in the host, which can be used as specific biomarkers of exposure to Anopheles sundaicus . The objective of this study was to identify immunogenic proteins from the salivary glands of Anopheles sundaicus by reaction with sera from individuals living in malaria-endemic areas who are thus exposed to Anopheles mosquitoes.METHODS:IgG antibodies targeting salivary gland proteins in serum samples from individuals living in malaria-endemic areas were measured by enzyme-linked immunosorbent assay (ELISA). Sera from healthy individuals living in non-endemic areas were used as negative controls. Determination of the presence of salivary gland immunogenic proteins was carried out by western blotting.RESULTS:Sixteen bands appeared in sodium dodecyl sulfate polyacrylamide gel electrophoresis, with molecule weights ranging from 22 to 144kDa. Among the exposed individuals, IgG responses to salivary gland proteins were variable. Protein bands with molecular weights of 46, 41, 33, and 31kDa were the most immunogenic. These immunogenic proteins were consistently recognized by pooled serum and individual samples from people living in malaria-endemic areas but not by negative controls.CONCLUSIONS:These results support the potential use of immunogenic proteins from the salivary glands of Anopheles as candidate markers of bite exposure or in malaria vaccines.

Basic sanitation, socioeconomic conditions, and degree of risk for the presence and maintenance of malaria in a low-transmission area in the Brazilian Amazon

ABSTRACTINTRODUCTION:This study aimed to evaluate basic sanitation and socioeconomic indicators, reported cases of malaria, and risk of contracting malaria in the Ananindeua municipality, State of Pará.METHODS:Data on basic sanitation and socioeconomic dimensions were taken from the Brazilian Institute of Geography and Statistics [ Instituto Brasileiro de Geografia e Estatística (IBGE)] 2010 census. Epidemiological malaria information was taken from the Epidemiological Malaria Surveillance Information System [ Sistema de Informação de Vigilância Epidemiológica de Malária (SIVEP/Malaria)], between 2003 and 2013 of the Ministry of Health and from the SIVEP/Malaria forms of the municipality's Endemic Diseases Unit for 2,013 cases.RESULTS:Our data do not confirm the correlation among indicators of basic sanitation, socioeconomic conditions, and water supply with malaria cases. Of the 1,557 cases evaluated, most were caused by Plasmodium vivax , with rare cases of Plasmodium falciparum and mixed infections. There were 756 notifications in 2003. The number of reported cases was sharply reduced between 2006 and 2012, but a 142-case outbreak occurred in 2013. Ananindeua municipality's Annual Parasite Index indicated low risk in 2003 and no risk in other years, and the 2,013 cases were predominantly male individuals aged ≥40 years.CONCLUSIONS:Our data confirm the non-endemicity of malaria in the Ananindeua municipality, as the Annual Parasite Indices described for the years 2004-2013 classify it as a risk-free area. However, the 2013 outbreak indicates the need to strengthen prevention, surveillance, and control activities to reduce the risk of new outbreaks and consequent economic and social impacts on the population.

Clinical and serological outcomes with different surgical approaches for human hepatic hydatidosis

ABSTRACTINTRODUCTION:Hydatidosis is the result of infection with the larval stages of some species of the genus Echinococcus. Treatment approaches for hydatid cysts include the use of albendazole, surgery, and/or medico-surgical procedures. The choice of the therapeutic surgical approach depends on the cyst number and localization, surgeon expertise, and presence of complications. The present study aimed to compare the outcomes of the following therapeutic approaches for the treatment of hepatic hydatid cysts: pericystectomy; the puncture, aspiration, injection, and reaspiration (PAIR) technique; and the PAIR technique followed by deroofing, evacuation of cysts, and omentoplasty.METHODS:The 54 patients were divided into 3 groups: Group I (14 patients) who underwent pericystectomy, Group II (23 patients) who underwent the PAIR technique, and Group III (17 patients) who underwent the PAIR technique followed by deroofing and omentoplasty. The diagnosis of hydatid cysts was based on serological testing using enzyme-linked immunosorbent assay, abdominal ultrasound, and parasitological examination of the cyst contents. Morbidity, mortality, length of hospital stay, recurrence, and postoperative complications were evaluated.RESULTS:Postoperative bleeding, infection, and recurrence were reported in Groups I and II; Group III did not experience postoperative infection and had shorter hospital stays. Recurrence and postoperative complications did not occur in Group III.CONCLUSIONS:The partial surgical procedure with deroofing, evacuation of the cysts, and omentoplasty, as performed in the present study, is recommended as a safe and effective method for elimination of the entire parasite with minimal possibility for intra-peritoneal spillage.