Arlene de Jesus Mendes Caldas

Seroconversion against Lutzomyia longipalpis Saliva Concurrent with the Development of Anti–Leishmania chagasi Delayed-Type Hypersensitivity

Antibody responses to salivary gland sonicate (SGS) from Lutzomyia longipalpis were investigated using serum samples from individuals living in an area where visceral leishmaniasis is endemic. Individuals were classified into 2 groups, according to the alteration of their responses to Leishmania chagasi antigen over the course of 6 months. Group 1 included children who experienced anti-L. chagasi seroconversion from negative to positive; group 2 included children who experienced delayed-type hypersensitivity (DTH) response to L. chagasi antigen conversion from negative to positive. Individuals who experienced seroconversion against L. chagasi antigens did not have increased anti-saliva antibody response, whereas those who developed a positive anti-L. chagasi DTH response had increased immunoglobulin (Ig) G, IgG1 and IgE anti-SGS antibody levels. Despite wide variation, serum samples from individuals in group 2 recognized more bands in SGS than did those from individuals in group 1. This simultaneous appearance of anti-saliva humoral response and anti-L. chagasi cell-mediated immunity supports the hypothesis that induction of immune response against SGS can facilitate induction of a protective response against leishmaniasis.

Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis

BackgroundLeishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis.MethodsTo explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels.ResultsElevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients.ConclusionTaken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

Background Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. Methodology/Principal Findings We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. Conclusions/Significance Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

Risk factors associated with asymptomatic infection by Leishmania chagasi in north-east Brazil

Various factors have been associated with a predisposition to the development of clinical American visceral leishmaniasis (AVL). However, little information is available about the factors that predispose to asymptomatic infection. To identify the risk factors associated with asymptomatic infection, a study was carried out between July 1997 and June 1998 on children aged 0-5 years in the districts of Vila Nova and Bom Viver in the municipality of Raposa in the island of São Luís, State of Maranhão, Brazil. A questionnaire containing socioeconomic, demographic and epidemiological data was used. The delayed-type hypersensitivity (DTH) test was carried out on 639 children in the first phase, and on 572 in the second, 7 months after the first survey, using Leishmania amazonensis antigen. Infection was determined by enzyme-linked immunosorbent assay (ELISA) in 638 children during the first phase, and in 572 during the second. Six outcome measures were used: initial prevalence, final prevalence and incidence, each determined by DTH and ELISA. The incidence of infection was 10.8% when determined by DTH and 28.5% when determined by ELISA. After adjustment for confounding variables using Cox regression, infection by L. chagasi was associated with childs age (> or = 2 years), location of the dwellings (Vila Nova) and reporting of relatives with AVL. Bathing outside the house and playing outdoors between 18:00 and 20:00 were identified as risk factors in some analyses but not in others. Presence of intra- and peridomestic Lutzomyia sandflies and animals such as dogs or chickens in the house or in the neighbourhood appeared as risk factors in some analyses but in others they unexpectedly seemed to protect from infection. Malnutrition was not found to be associated with infection.

Investigations on magnetic refrigeration: Application to RNi2 (R=Nd, Gd, Tb, Dy, Ho, and Er)

In this article we report the thermodynamic investigations on the Ericsson cycle with application on RNi2 (R=Nd, Gd, Tb, Dy, Ho, and Er) series. Besides the Zeeman and exchange interactions, these compounds present an important contribution from crystalline electrical field interaction. The Ericsson coefficient of performance and refrigerant capacity was investigated under the crystal field influence. An optimum molar composite of Er–Dy–TbNi2 was proposed to work as refrigerant material in the temperature interval from 7 to 22 K.

Perfil dos pacientes com hanseníase em área hiperendêmica da Amazônia do Maranhão, Brasil

An epidemiological cross-sectional study of 207 patients with leprosy disease, was undertaken between August 1998 to november 2000, aiming at evaluating the socioeconomic, demographic and ambiental profiles of the patients as well as physical incapacity due to the disease. The study was performed in the municipality of Buriticupu-Maranh o state, a hiperendemic leprosy area in the Amazonian Maranh o. The level of incapacity was assessed from parameters established by the Brazilian Health Minister. The clinical evaluation and the results of the physical tests were registered in a standardized form. It was observed a predominance of married people (45,9%), with low level of education (56%), being lend workers (40,1%), with familiar income to the minimum wage (76,3%), aged from 14 to 44 years (63,3%), males (60,9%) and brown (67,6%); 44% living in mud huts, 82,6% deposited their excrements in cesspits and 63,8% do not treat the drinking water, 58% utilized well-water and 51,7% do not use treated water for ingestion. The most affected segments of the body were the feet (62,3%), eyes (51,2%) end hands (7,2%), being the higher percentage of physical incapacitaties found among the patients bearing the borderline form of the disease (93%) mainly hands and feet, and in the virchowian form greatest frequency of eyes incapacities. It is concluded that the hyperendemicity associated with the precarious socioeconomic conditions and with a high level of physical incapacities may be involved with the living quality of the patients.An epidemiological cross-sectional study of 207 patients with leprosy disease, was undertaken between August 1998 to november 2000, aiming at evaluating the socioeconomic, demographic and ambiental profiles of the patients as well as physical incapacity due to the disease. The study was performed in the municipality of Buriticupu-Maranhao state, a hiperendemic leprosy area in the Amazonian Maranhao. The level of incapacity was assessed from parameters established by the Brazilian Health Minister. The clinical evaluation and the results of the physical tests were registered in a standardized form. It was observed a predominance of married people (45,9%), with low level of education (56%), being lend workers (40,1%), with familiar income to the minimum wage (76,3%), aged from 14 to 44 years (63,3%), males (60,9%) and brown (67,6%); 44% living in mud huts, 82,6% deposited their excrements in cesspits and 63,8% do not treat the drinking water, 58% utilized well-water and 51,7% do not use treated water for ingestion. The most affected segments of the body were the feet (62,3%), eyes (51,2%) end hands (7,2%), being the higher percentage of physical incapacitaties found among the patients bearing the borderline form of the disease (93%) mainly hands and feet, and in the virchowian form greatest frequency of eyes incapacities. It is concluded that the hyperendemicity associated with the precarious socioeconomic conditions and with a high level of physical incapacities may be involved with the living quality of the patients.

Infecção por Leishmania (Leishmania) chagasi em crianças de uma área endêmica de leishmaniose visceral americana na Ilha de São Luis-MA, Brasil

Barral, Aldina Maria Prado “Documento produzido em parceria ou por autor vinculado a Fiocruz, mas nao consta a informacao no documento”.A prospective study was undertaken in 648 children with less than 6 years of age in the municipality of Raposa, Maranhao, Brazil, from June 1997 to June 1998, to evaluate the characteristics of the infection by L.(L.)chagasi and verify if there is an association between malnutrition and asymptomatic infection. A standardized questionnaire was used containing socioeconomic, environmental and behavioral data. Montenegro skin reaction (IDRM) with L. amazonensis and Enzyme Linked Immunosorbent Assay (ELISA) test to detect infection, and anthropometric examination were performed. Initial and final prevalence and incidence of infection were 18.6%, 20.6% and 10.8% as measured by IDRM and 13.5%, 34.4% and 28% according to ELISA. The prevalence of chronic malnutrition was 26%. No association was detected between malnutrition and asymptomatic infection by L. (L.) chagasi. More effective control measures are needed in these areas since asymptomatic infection seems to be on the increase.

Multi-centric prospective evaluation of rk39 rapid test and direct agglutination test for the diagnosis of visceral leishmaniasis in Brazil.

The diagnosis of visceral leishmaniasis (VL) is still a major problem in Brazil and several other countries where the disease is endemic. The use of an easy-to-use and interpret, sensitive, and specific method that requires no complex infrastructure or specialized professionals, such as direct agglutination test (DAT) and the rK39-based rapid immunochromatographic test may enhance the diagnosis of disease. This study evaluated the performance of a rapid test (DiaMed- IT-LEISH®) and the DAT for the diagnosis of VL in 213 parasitologically confirmed cases and 119 controls with clinical suspicion of VL and confirmation of another etiology. The sensitivities and specificities of the rapid test were 93% and 97%, respectively and those of the DAT were 90% and 96%, respectively. The positive predictive values of the rapid test and the DAT were 98% and 97%, respectively and the negative predictive values were 89% and 84%, respectively. The Kappa index showed agreement between both methods classified as substantial (0.77). This study showed that the DAT and the rapid test can be used to diagnose VL in Brazil, following a pilot study for implementation of the rapid test in the health services.

Validação do teste imunocromatográfico rápido IT-LEISH® para o diagnóstico da leishmaniose visceral humana

The rapid immunochromatographic test IT-LEISH® (DiaMed IT-LEISH) was validated for the diagnosis of visceral leishmaniasis (VL) in four endemic areas of Brazil. The performance of the IT-LEISH® was compared with that of the indirect fluorescent antibody test, and that of enzyme-linked immunosorbent assay, using soluble antigen of Leishmania chagasi and the recombinant K39 (rK39). The study group was composed by 332 patients with clinical suspicion of VL: 213 cases confirmed by parasitological tests; and 119 with confirmation of another etiology. The sensitivity of the test IT-LEISH® was of 93% and the specificity of 97%. Immunofluorescent antibody test, ELISA L. chagasi and ELISA rK39 showed sensitivity of 88%, 92%, and 97%, and specificity of 81%, 77%, and 84%, respectively. The results confirm the validity of the test IT-LEISH® for the diagnosis of the VL in Brazil.

Epidemiological, clinical, and operational aspects of leprosy patients assisted at a referral service in the state of Maranhão, Brazil

INTRODUCTION Leprosy is an infectious disease caused by Mycobacterium leprae. The aim of this study was to describe the epidemiological, clinical, and operational aspects of leprosy carriers. METHODS A cross-sectional study leprosy patients assisted in São Luis, MA, was performed. RESULTS Of the 85 cases analyzed, 51.7% were male participants, and 60% were brown. Concerning the age, 54.8% of women were between 35 and 49 years, and 57.6% of men were between 20 and 34 years. Lepromatous leprosy was found in 42.3% of cases, and the multibacillary form was found in 72.9%. The skin smear was positive in 42.3%. The occurrence of reaction was found in 43.5% of cases, and 83.5% had no Bacillus Calmette-Guérin scar. Leprosy in the family was reported by 44.7% of the patients. Most of the individuals (96.4%) lived in houses made of brick with more than three rooms (72.6%) and two persons per room (65.1%). Concerning the level of education, 41.4% of women and 34.1% of men had more than one to three years of education. The most evaluated age group in the beginning of the treatment was that of 35 to 49 years with a Grade 0 incapability (64.5%), and that in the end was the age group of 20 to 34 (29.9%) with Grade 0, 30.7% Grade 1, and 11.5% Grade 2. CONCLUSIONS The frequency of multibacillary forms found in this study and the cases in family members point out delayed diagnoses. Thus, early diagnosis and appropriate treatment are important in decreasing the outcome of disabilities.