Ensaios terapêuticos com penicilina V-Bouba (Framboesia, pian, yaws): I - Dose curatina mínima: II - Redução do número de injeções diarias: III - Redução de tempo de tratamento pelo emprêgo de doses mais elevadas

This report belongs to the series of works carried out Oswaldo Cruz Ins¬titute, on the treatment of treponematosis with penicillin. The present report deals with investigations performed in order to ascer¬tain the following points: 1) the mininal curative dosis for the initial lesions of yaws; 2) the effect of reduction of the number of injections each day, to verifie the possibility of application of penicillin in the prophylaxis of yaws in rural zones; 3) reduction of the time of treatment by application of high dosis. 1) With dosis of 150 and 100 Oxford units each four hours, clinical reco¬very was obtained after 17 days of treatment. With 50 O.u. during 40 days clinical recovery was not obtained. 2) a) With 3 injections of 400 O.u. each day (6,12 and 18 hoórs clocks) clinical recovery was obtained after 14 to 16 days; b) with 2 injections of 400 O.u. each day (6 and 18 hoors clocks), clinical recovery was obtained after 16 to 23 days; c) with 1 injection of 1.600 and 3.200 each day, clinical recovery was obtained after 30 and 20 days. 3) With dosis of 33.3 and 46.7 O.u. by each kilo of weight each four hours, during 15 days, clinical recovery was obtained more or less in 25 days. The same result was obtained with the dosis of 61.5 and 166.7 O.u. by each kilo of weight, each four hours, during 4 days. But with 100.000 O.u. in fine dosis of 20.000 in a day ou by, clinical recovery was not obtained.

A simple and economic slide micro-immunoenzymatic (Micro-SIA) test for epidemiological studies of toxoplasmosis

A slide micro-immunoenzymatic assay (micro-SIA) to detectantibodies to non-particulate Toxoplasma gondii antigens is described. This assay allows the diagnosis of toxoplasmosis infection in about 1 hr. Twenty-four determinations can be performed per slide. Five hundred ng of antigen and 5 or 10 µl drop of each reactive are necessary per well. The clear contrast of colours obtained for negative and positive sera after the test is finished, allows direct discrimination of the results. However, it is possible to quantify the results of the reaction using a minireader. Sera dilution cutoff value, determined as themost frequent titre for the general population, is 1:100. The toxoplasma micro-SIA correlates well with indirect immunofluorescence (IIF), its sensitivity is atleast three times as much as IIF. The test has an intra and inter assay variation coefficient of 5.46 per cent and of 6.24 per cent respectively. Sera obtained at random from argentinian people were analyzed and a 56 per cent of infection was found. The main features of the Toxoplasma micro-SIA are its simplicity, sensitivity, reproducibility, and the virtual absence of background making it very suitable for screening tests.

High and low doses of antimony (Sb v) in American cutaneous leishmaniasis: a five years follow-up study of 15 patients

Seventeen patients proceeding from the municipality of Rio de Janeiro, Brazil presenting with the cutaneous ulcerative form of American leishmaniasis were treated with one ampoule of pentavalent antimony daily for 30 days. With this regimen the individuals doses varies greatly: from 3.8 mg/kg of body weight to 22.3 mg/kg. After five years, patients receiving either a smaller dose or a bigger one, showed the same therapeutic result: cutaneous scars and no mucosal lesions.

Fecundity Changes Induced by Low-Doses of Gamma Radiation on Biomphalaria straminea (Dunker, 1848)

A population of 420 snails Biomphalaria straminea, an intermediate host of Schistosoma mansoni, received gamma-rays obtained from a 60Co source in low-doses (0/2,5/5/7,5/10/15/20 and 25 Gy); half population was kept in colonies (allowing cross fertilization) and the other half was mantained in sexual isolation (allowing self fertilization). Results showed that 15 Gy stimulates the fertility of both groups but the colonies were more sensitive and at this dose its fertility overpasses the control group dose. The possible hormonal role played in the observed phenomena is under investigation

Intradermal vaccination of adults with three low doses (2 µg) of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects

A total of 250 dentists (53.6% men and 46.4% women), with a mean age of 35.1 ± 9.8 years, were submitted to serological tests for the diagnosis of hepatitis B (HB) - HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe - using a radioimmunoassay. One or more of these markers were detected in 78 individuals (31.2%) who were excluded from the group to be vaccinated. Of the 172 HB-susceptible individuals, 135 (78.5%) responded to the call and were intradermally injected with three 2 µg doses of the Belgian HB recombinant vaccine, applied at an interval of one month between the 1st and 2nd dose and of five months between the 2nd and 3rd dose. A new determination of HB markers carried out 50 days after the 3rd dose showed that 110 (81.5%) individuals had become anti-HBs positive (65.5% good responders and 34.5% poor responders). Mean serum anti-HBs titer of these 110 dentists was 42.4 U S/N, similar in both sexes. The adverse effects analyzed in 106 dentists were: (a) local: pain (12.3%), burning sensation (14.1%), pruritus (25.5%), erythema (28.3%), local heat (18.9%), and a hypochromic spot (32.1%); (b) systemic (4.7%): discomfort in two patients, and fever, anorexia, and asthenia in one patient each. Intradermal administration of a fourth 2 µg vaccine dose to 39 dentists (poor or non-responders) increased the total number of anti-HBs-positive individuals from 110 (81.5%) to 114 (84.4%), with the number of good responders increasing from 72 (65.5%) to 85 (74.6%). We conclude that the Belgian recombinant vaccine applied in the scheme used here induces a high rate of seroconversion and causes only mild and transitory adverse effects.

Intradermal vaccination of adults with three low doses (2 µg) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 µg doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 µg booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB - with intra-dermal application of three 2 µg doses of the Belgian recombinant vaccine at 0, 1, and 6 months - carried out eight years before in 51 dentists.

A micro-spreading improvement for spermatogenic chromosomes from Triatominae (Hemiptera-Reduviidae)

Cytogenetics of triatomines have been a valuable biological tool for the study of evolution, taxonomy, and epidemiology of these vectors of Trypanosoma cruzi. Here we present a single microtube protocol that combines micro-centrifugation and micro-spreading, allowing high quality cytogenetic preparations from male gonadal material of Rhodnius prolixus and Triatoma lecticularia. The amount of cellular scattering can be modulated, which can be useful if small aggregates of synchronous cells are desired. Moreover, a higher number of slides per gonad can be obtained with fully flattened clean chromosomal spreads with minimum overlaps, optimal for classical and modern molecular cytogenetic analyses.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.

Spatial distribution of Schistosoma mansoni infection before and after chemotherapy with two praziquantel doses in a community of Pernambuco, Brazil

Praziquantel chemotherapy has been the focus of the Schistosomiasis Control Program in Brazil for the past two decades. Nevertheless, information on the impact of selective chemotherapy against Schistosoma mansoni infection under the conditions confronted by the health teams in endemic municipalities remains scarce. This paper compares the spatial pattern of infection before and after treatment with either a 40 mg/kg or 60 mg/kg dose of praziquantel by determining the intensity of spatial cluster among patients at 180 and 360 days after treatment. The spatial-temporal distribution of egg-positive patients was analysed in a Geographic Information System using the kernel smoothing technique. While all patients became egg-negative after 21 days, 17.9% and 30.9% reverted to an egg-positive condition after 180 and 360 days, respectively. Both the prevalence and intensity of infection after treatment were significantly lower in the 60 mg/kg than in the 40 mg/kg treatment group. The higher intensity of the kernel in the 40 mg/kg group compared to the 60 mg/kg group, at both 180 and 360 days, reflects the higher number of reverted cases in the lower dose group. Auxiliary, preventive measures to control transmission should be integrated with chemotherapy to achieve a more enduring impact.

Residual effect of a micro-encapsulated formulation of organophosphates and piriproxifen on the mortality of deltamethrin resistant Triatoma infestans populations in rural houses of the Bolivian Chaco region

The Bolivian Chaco is part of the endemic region of Chagas disease and an area where pyrethroid resistant Triatoma infestans (Hemiptera: Reduviidae) populations has been reported. The World Health Organization identified these resistant populations as an important focus for research. The objective of this study was to evaluate the residual effect of a micro-encapsulated formulation containing organophosphate active ingredients and a juvenile hormone analogue (Inesfly 5A IGR) on the mortality of T. infestans. Studies took place in rural houses of the Bolivian Chaco that were treated up to 34 months before and evaluated the susceptibility to pyrethroids of the offspring of field collected insects. Thirty houses were randomly selected within three communities to carry out wall bio-assays with T. infestans nymphs. Mortality was recorded 24, 48 and 72 h after wall contact. Eggs laid by females collected in the area were used to obtain first-instar nymphs and carry out pyrethroid susceptibility tests. The wall bio-assays showed that the micro-encapsulated insecticide eliminates T. infestans populations and produces detectable mortality of insects exposed to walls treated 34 months prior to the tests. The discriminant dose of deltamethrin (0.01 mg/mL) showed 65% nymph survival, whereas at the highest tested dose (1.0 mg/mL) 14% of the nymphs survived. These results show that Inesfly 5A IGR is an appropriate tool for the elimination of intradomestic and peridomestic populations of T. infestans resistant to pyrethroids.

Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

Determinantes da participação e sucesso das micro e pequenas empresas em compras públicas: uma análise empírica

RESUMO Tendo como base discussões recentes sobre as relações entre estratégia e desempenho no setor público, no presente trabalho analisam-se os condicionantes da participação e do sucesso de micro e pequenas empresas (MPE) em compras públicas a partir de alterações na legislação, favorecendo tais grupos. Adota-se uma abordagem de natureza quantitativa e desenvolve-se um conjunto de hipóteses, que são testadas usando uma base de dados única, com informações detalhadas de 542 contratos de compras realizados por um órgão da administração pública federal brasileira, entre 2005 e 2011. Os resultados demonstraram que as mudanças institucionais, promovidas por uma nova regulamentação, contribuíram significativamente para o aumento na participação de MPE nos processos de licitações do órgão pesquisado, porém não alteraram a probabilidade de êxito dessas empresas nos certames públicos, colocando em perspectiva a eficácia da legislação implantada. Adicionalmente, os resultados sugeriram que fatores estratégicos, associados ao ambiente competitivo, aos atributos transacionais e às capacidades inerentes aos participantes, influenciam seu acesso e as chances de sucesso em compras públicas.