Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

A comparative study of four serological methods for diagnosis of acute and chronic Chagas' disease in Brazilian patients.

Complement fixation (CF), indirect immunofluorescence (IFAT), latex agglutination (LA) and the enzyme-linked immunosorbent assay (ELISA) were applied to assess the diagnostic value of antibody determination in Brazilian patients with acute or chronic Chagas' disease. Patients with various forms of leishmaniasis and healthy individuals from the endemic region were used as specificity controls. Whereas LA, IFAT and ELISA identified 81% of acutely ill patients, CF had no diagnostic potential in this phase of the disease. In later stages CF showed a sensitivity of 69% as compared to 100% for LA, IFAT and ELISA, irrespective whether patients presented clinically as chronic asymptomatic or chronic symptomatic cases. Cross-reactivity with anti-leishmania antibodies was observed in 23%, 38% and 77% of serum samples in LA, ELISA and IFAT, respectively, but not in CF.

Phlebotomine sandfly (Diptera: Psychodidae) fauna survey in an American cutaneous leishmaniasis (ACL) focus in Baturité, Ceará State, northeast Brazil.

From October until July 1991, CDC miniature light traps were set up and man and animal-landing and biting catches were made in 100 different catching zones, in different habitats, throughout the ACL focus of the Serra de Baturité. Female Lutzomyia whitmani and Lu. wellcomei appeared to be highly anthropophilic and were the most prevalent species in man-landing catches in peridomestic sites. Most Lu. migonei were attracted to animals, especially mules. Seasonal fluctuations and habitat preference were noted for the principal populations present.

Evaluation of antibody responses in American visceral leishmaniasis by ELISA and immunoblot.

American visceral leishmaniasis (AVL) is an important disease among children of northeast Brazil. In order to characterize antibody responses during AVL, sera of hospitalized patients were analyzed by ELISA and Western blot using a Leishmania chagasi antigen preparation. The ELISA was positive (absorbance greater than or equal to 0.196) at a serum dilution of 1:1024 in all patients at presentation, and fell to ward control levels over the following year. Only one of 72 control subjects tested positive, and that donor had a sibling with AVL. Immunoblots of the patients' sera recognized multiple bands, the most frequent of which were at approximately 116 kDa, 70 kDa, and 26 kDa. Less frequently observed were bands at approximately 93 kDa, 74 kDa, 62 kDa, 46 kDa and 32 kDa. The ELISA responses and patterns of banding were distinctive for AVL, and could be used to differentiate patients with AVL from those with Chagas' disease or cutaneous leishmaniasis. Sera from six AVL patients followed for up to six weeks after treatment identified no new bands. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of surface iodinated parasite proteins showed one major band and four minor bands, whereas SDS-PAGE of biotinylated parasite proteins revealed a banding pattern similar to those of patient sera. AVL appears to produce characteristic immunoblot patterns which can be used along with a sensitive screening ELISA to diagnose AVL.

Epidemiological studies on American leishmaniasis in Ceará State, Brazil. Molecular characterization of the Leishmania isolates.

Two methods of molecular characterization, using monoclonal antibodies and enzyme electrophoresis, were employed in the identification of 36 stocks of Leishmania isolated from human and canine cases of American visceral (AVL) and cutaneous (ACL) leishmaniases in the northern part of Ceará State, Brazil. Molecular homogeneous strains of Leishmania donovani (chagasi) isolated from both human and canine hosts were detected in 14 municipalities. Two more parasite species, L. braziliensis braziliensis and L. mexicana amazonensis, were also detected in the state. The implication of these results with respect to both the clinical and epidemiological data are discussed.

Liver involvement in human schistosomiasis mansoni. Assessment by immunological and biochemical markers.

In 20 patients with hepatic or hepatosplenic schistosomiasis and 82 individuals infected with S. mansoni, but without liver enlargement, serum parameters reflecting the fibrotic process and hemodynamic alterations as well as immunomodulation were examined. Included as controls were 35 age- and sex-matched healthy individuals from the study region in Northeast Brazil. Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement. Procollagen-III-peptide, a cleavage product of collagen synthesis, was elevated in patients with hepatomegaly (P less than 0.001) but normal in uncomplicated cases. Immunomodulation was assessed by in vivo delayed hypersensitivity to recall antigens and by serum beta 2-microglobulin and neopterin, substances released in the context of lymphocyte activation. Neopterin, predominantly a macrophage product, was elevated most strikingly in hepatomegalic cases (P less than 0.001). The possible interrelation between altered immune responses and excess fibrogenesis is discussed.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in Schistosomiasis mansoni in Brazil

Conduziu-se um ensaio clínico para comparar a eficácia de uma combinaçäo em baixo doses de oxamniquine (7,5 mg/kg) mais praziquantel (20 mg/kg) com ambas as drogas - oxamniquine (15 mg/kg) e praziquantel (40 mg/kg) - empregadas isoladamente, no tratamento da esquistossomose mansônica em uma área endêmica do nordeste brasileiro. Os medicamentos foram administrados, aleatoriamente, por via oral, a 91 pacientes. Seis e doze meses depois do tratamento 89% dos admitidos no ensaio foram reexaminados segundo os métodos de Kato-Katz (dez lâminas) e MIF (um grama de fezes). Os índices de cura alcançados, representando a ausência de ovos nas fezes em todos os controles durante o acompanhamento parasitológico individualizado dos pacientes, foram de 81,8%, 81,2% e 67,6% com, respectivamente, o praziquantel, a oxamniquine e a combinaçäo. A reduçäo do número de ovos eliminado por grama de fezes nos casos näo curados, variou de 93,8-96,8% com o praziquantel, 32,5-97% com a oxamniquine e 76,9-99,5% com a combinaçäo. Concluiu-se que os três regimes terapêuticos, nas doses utilizadas, däo resultados similares e satisfatórios no tratamento da esquistossomose mansônica näo complicada, no Brasil

Detection and quantification of circulating antigen in schistosomiasis by monoclonal antibody. II. The quantification of circulating antigens in human schistosomiasis mansoni and haematobium: relationship to intensity of infection and disease status.

Circulating cathodic and circulating anodic antigens were quantified in sera of patients infected with S. mansoni, S. haematobium or both parasites. A monoclonal antibody and a polyclonal antiserum were applied in precipitation and solid phase immunosorbent techniques using radio- and enzyme-labelled antibody as a tracer to detect the cathodic and anodic antigen respectively. The results show that circulating cathodic antigen can frequently be detected in an immunoprecipitation or an immunoradiometric assay in serum of infected patients. The serum concentration of this antigen was found to be significantly correlated to the number of S. mansoni worms and to be higher in patients with the hepatosplenic form of the disease than in those without such complications. Examining paired serum samples before and after specific treatment the determination of this antigen by monoclonal antibody reliably indicated efficacy of chemotherapy in patients having received different forms of treatment.

Reciprocal relationships between undernutrition and the parasitic disease visceral leishmaniasis.

Little is known about the interrelationship between undernutrition and parasitic infections in areas of the world where both are prevalent. The associations between undernutrition and visceral leishmaniasis, an important protozoal disease, were assessed in a study of residents of an area in Brazil with endemic leishmaniasis. Mid-arm anthropometry was used to assess fat and muscle area. Children with visceral leishmaniasis came from large families (9.6 +/- 1.1 members vs. 6.8 +/- 0.7 members in neighborhood control families), and patient housemates had fat areas that were 78% (P less than .05) those of age- and sex-matched neighborhood controls. The children with visceral leishmaniasis who were studied four months or less after diagnosis had fat areas that were 66% (P less than .05) those of age- and sex-matched household controls or 41% (P less than .01) those of neighborhood controls and muscle areas that were 81% (P less than .025) those of household controls or 75% (P less than .05) those of of neighborhood controls. It is hypothesized, on the basis of these data and other findings, that undernutrition is associated with the development of clinically apparent visceral leishmaniasis and that the disease itself has a profound effect on nutritional status, resulting in loss of both muscle and fat, effects that possibly are mediated by interleukin-1 and/or other factors produced by Leishmania donovani-infected macrophages.

American visceral leishmaniasis (kala-azar).

Visceral leishmaniasis (kala-azar) is an important cause of morbidity and mortality in widely scattered areas of the world. To better characterize the South American form of the disease, the clinical and laboratory manifestations of 29 patients admitted to hospital (18 male and 11 female patients, mean age 4.9 years), were assessed in an endemic area in northeastern Brazil. Fever, weight loss, pronounced splenomegaly, hepatomegaly, anemia, thrombocytopenia, relative neutropenia, hypoalbuminemia and hypergammaglobulinemia were found in the majority of patients. Symptoms were often present for two or more months before diagnosis. Secondary infections complicated many cases; there were ten cases of pneumonia and half of the patients had one or more intestinal parasites. The average length of hospital stay was 27 days; all patients were treated with meglumine antimoniate (Glucantime). The mortality rate was 3%. American visceral leishmaniasis remains an important disease among children living in endemic areas.

The relationship of American visceral leishmaniasis to ABO blood group type.

It has been hypothesized that the Leishmania use a system of camouflage or mimicry of human ABO blood group antigens to evade host defense mechanisms. In order to test this hypothesis, the distribution of ABO blood groups among healthy control donors and among patients with visceral leishmaniasis in northeastern Brazil was compared. No significant differences were found between patients with American visceral leishmaniasis and controls, indicating that ABO blood group type is not an important determinant in the development of clinically apparent visceral leishmaniasis in that area. The findings raise doubt about the validity of the original hypothesis.

Presence of Psychodopygus wellcomei (Diptera: Psychodidae), a proven vector of Leishmania braziliensis braziliensis, in Ceara State.

Psychodopygus wellcomei, um vetor comprovado de leishmaniose (muco) cutanea, foi pela primeria vez encontrado fora da Bacia Amazonica, no Estado do Ceara. Evidencia parasitologica e entomologica sugere que a Leishmania braziliensis braziliensis transmitida pelo Ps. wellcomei encontra-se largamente espalhada no "Macico montanhoso do Brasil"