Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil

A clinical trial pilot study, double-blinded, randomized, and controlled with a placebo to assess the effectiveness of oral doxycycline (200 mg, single dose) in preventing leptospirosis after high exposure to potentially contamined water was performed in São Paulo, SP, Brazil. Confirmed cases were defined as those with leptospira IgM antibody and symptoms; asymptomatic cases were those presenting with IgM antibodies but no symptoms; and suspected cases were individuals with symptoms but no IgM antibody. Forty subjects were given doxycycline and 42 were given placebo. In the drug-treated group there were 2 confirmed cases, 11 asymptomatic cases, and 6 suspected cases. In the placebo group there were 5 confirmed, 6 symptomatic, and 5 suspected cases. Even though we found a protective association of doxycycline for confirmed leptospirosis cases (RR = 2.3) and seroconversion only (RR = 2.0), the association was not statistically significant because of the small number of individuals enrolled in this pilot study. We observed that the 22% of the volunteers already had IgM antibodies to leptospirosis at the first sampling. Finally, the attack rate to confirmed, asymptomatic, and suspected cases of Leptospirosis was 8.5%, 22%, and 13%, respectively, in this population.

Thiamphenicol in the treatment of chancroid. A study of 1,128 cases

Thiamphenicol, an aminic derivate of hydrocarbilsulfonil propandiol, was used for the treatment of 1,171 chancroid bearing patients. Each patient was medicated with 5.0 g of granulated thiamphenicol, orally, in a single dose, and was reevaluated 3, 7 and 10 days after the treatment. Ten patients (0.89%) did not respond to the proposed treatment. 133 patients presented healed ulcers after 3 days of treatment, 976 patients healed chancres on the seventh day after the treatment, and 39 patients took 10 days to present healed chancres. The results of this study indicate that the rate of patients that were cured, the low incidence of side effects, and the practicality of administration make of thiamphenicol an excellent choice for the treatment of chancroid.

Significance of isolated hepatitis B core antibody in blood donors from São Paulo

The clinical significance of isolated anti-HBc is still a challenge. To elucidate the real importance of this finding in our blood donors, an investigation algorithm was tested. One hundred and twelve isolated anti-HBc seropositive blood donors underwent clinical evaluation and retesting of HBV markers. Those who presented repeatedly reactive isolated anti-HBc, received a single dose of hepatitis B recombinant vaccine to verify anti-HBs early response. A HBV-DNA determination by PCR was done for those who did not test positive to anti-HBs after vaccine. The level of anti-HBc was recorded as a ratio of the sample-to-cut-off values (S:C ratio) in 57 candidates at donation. Comparing true and false-positive anti-HBc results, the different S:C ratios of them were statistically significant and when less than 2, implying in a false-positive result probability over 80%. A high percent of false-positive results (16.07%) was verified after anti-HBc retesting. HBV immunity was characterized in 49.11%, either by anti-HBs detection in retesting (15.18%), or after a single dose HBV vaccination (33.93%). HBV-DNA was negative in all tested donors. In conclusion, this algorithm was useful to clarify the meaning of isolated anti-HBc in most of our blood donors.

Cystoscopy in the diagnosis and follow-up of urinary schistosomiasis in Brazilian soldiers returning from Mozambique, Africa

The assessment of urinary schistosomiasis in individuals coming from endemic areas often requires diagnostic resources not used in areas of exposure in order to determine complications or to establish more precise criteria of cure. Cystoscopy and 24-hour urine examination were performed, after treatments with praziquantel 40 mg/kg body weight, single dose, on 25 Brazilian military men who were part of a United Nations peace mission to Mozambique in 1994. The median age of the individuals was 29 years and all presented a positive urine parasitological exam. The alterations detected by cystoscopy were hyperemia and granulomas in the vesical submucosa in 59.1% of the individuals and only granulomas in 40.9%. A vesical biopsy revealed granulomas in all patients and viable eggs in 77.3% even after a period during which the patients no longer excreted eggs in urine. Cystoscopy after treatment, followed by biopsy and histopathological evaluation, performed in areas where the evolution of the disease can be better monitored, was found to be a safe criterion of parasitological cure.

Schistosomiasis haematobia: histopathological course determined by cystoscopy in a patient in whom praziquantel treatment failed

Schistosomiasis haematobia or urinary schistosomiasis is one of the main public health problems in Africa and the Middle East. A single dose of 40 mg praziquantel per kg body weight continues to be the treatment of choice for this infection. The aims of this follow-up were to study the post-treatment course of a patient infected with S. haematobium and not submitted to re-exposure, and to identify complications of the disease and/or therapeutic failure after praziquantel treatment by histopathological analysis. Treatments were repeated under medical supervision to ensure the correct use of the drug. In view of the suspicion of lesions in cystoscopy, the patient was submitted to bladder biopsy. The histopathological characteristics observed in biopsies obtained, after each treatment, indicated viability of parasite eggs and activity of granulomas.

High occurrence of giardiasis in children living on a 'landless farm workers' settlement in Araras, São Paulo, Brazil

Enteric parasitosis remains an important public health problem in many areas around the world including in Brazil, and it is frequently associated with poverty and lack of sanitation facilities. Research carried out over the course of a year revealed that 96.6% (28/29) of children randomly selected from a 'landless farm workers' settlement in Araras, São Paulo, aged 4 - 15 years, presented Giardia intestinalis cysts. After referral to the neighborhood Health Office, all the children received tinidazole, given as a single dose of 50 mg/kg and 12 months later, new fecal samples were collected and analyzed. Despite the low adherence to the study, a high percentage (64.3% - 9/14) of the children remained positive for the parasite. This study showed a high positivity of giardiasis in child residents of the settlement, even after treatment; adults were not sensitized to the study and did not collected and/or deliver children fecal samples. The precarious living conditions are consistent with a high susceptibility to parasitic diseases, suggesting that the treatment of the infected individuals without identifying and eradicating the means of contamination is simply a palliative measure.

An attempt to control schistosomiasis mansoni in an endemic area by the use of Hycanthone as chemotherapeutic agent

Hycanthone in a single dose of 3.3 mg/kg of body weight was used to treal mansoni schistosomiasis in 597 persons (83%) of the population of the endemic vilage of Canabrava. Ninety two patients received a 2nd course 14 months later. There was one death em the 2nd treatment. The cure rate after one stool examination was smaller after the 2ni treatment in comparison with the first one. Re-infections did not occur imediately after the treatment. Three years later the prevalence of persons passing eggs through one stool examination was 19% compared to the 46.3% before the treatment. Adults are more resistant to the re-infections than younger.

Ultrastructural alterations of intracellular stages and effects on blood forms of Trypanosoma cruzi induced in vivo by 2-amino-5-(1-methyil-5-nitro-2-imidazolyl)-1,3,4 - Thiadiazole

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.

Estratégia de vacinação para eliminar o sarampo : um estudo sero-epidemiológico em diferentes populações vacinais

RESUMO - Introdução: As alterações epidemiológicas do sarampo em Portugal, assim como a existência de surtos de doença na Europa e noutras regiões do mundo, associadas ao facto de a informação sero epidemiológica atualizada ser escassa e pontual, e nem sempre estar relacionada com o estado vacinal, dificultam a tomada de decisões fundamentadas na área da vacinação, nomeadamente no que respeita às idades ótimas para a administração de VASPR I e VASPR II. Este estudo pretende avaliar a adequação da estratégia vacinal contra o sarampo vigente em Portugal, no que diz respeito às idades para realização da VASPR I e da VASPR II, no sentido de dar continuidade ao cumprimento do objetivo de eliminar a doença em território nacional. Material e métodos: Foi realizado um estudo com 206 recém-nascidos filhos de mães com diferentes estados vacinais contra o sarampo (0 doses, 1 dose e 2 doses). Também foram estudados 186 adolescentes/jovens que realizaram a VASPR II em diferentes idades. Os dados obtidos provêm de 3 fontes de informação: história vacinal documentada; questionários aplicados por entrevista e informação serológica. A informação serológica foi obtida através do doseamento do título de anticorpos específicos antissarampo (ATS IgG) em soros, recorrendo ao método imunoenzimático ELISA do kit Enzygnost® Anti-measles Virus/IgG, do fabricante Siemens. Resultados: A taxa de cobertura vacinal da vacina contra o sarampo aumentou de valores de pouco mais de 30% na geração nascida antes de 1977, com uma única dose de vacina, para valores superiores a 95 % na geração nascida depois de 1993, com duas doses de vacina. A concentração geométrica de ATS IgG no sangue do cordão umbilical aumentou com o aumento da idade da mãe (r2 = 0,092; p = 0,001). Os recém-nascidos filhos de mães vacinadas, apresentam menor quantidade de ATS IgG do que os filhos de mães não vacinadas (p < 0,0001), independentemente do número de doses que as suas mães tenham recebido (p = 0,222). A concentração geométrica média (CGM) de ATS IgG nos jovens e adolescentes diminui com o tempo decorrido desde a toma de VASPR II (r2 = 0,244; p = 0,001). Não foram encontradas diferenças estatisticamente significativas entre a média de ATS IgG dos indivíduos que se vacinaram com VASPR II aos 5-6 anos de idade e os que se vacinaram entre os 10-13 anos de idade (p = 0,301). Após 9 anos de VASPR II mais de 5 % dos indivíduos já não estão seropositivos contra o sarampo.Discussão: A CGM de ATS IgG aumentou com a idade da mãe, provavelmente porque as mães pertencentes às gerações mais novas contactaram menos com o vírus selvagem do sarampo, devido aos efeitos das elevadas taxas de cobertura vacinal. Os recém-nascidos filhos das mães mais novas, apesar de apresentarem menor CGM de ATS IgG, ao final de 12 meses de idade poderão ainda apresentar um teor de ATS IgG que pode interferir com a resposta vacinal à VASPR I. Vacinar com VASPR II aos 5-6 anos de idade ou vacinar entre os 10-13 anos parece ser indiferente o que parece relevante é o tempo que passa desde a última vacinação VASPR II. Nove anos depois de VASPR II a percentagem de seronegativos já ultrapassa os 5% recomendados pela OMS. Conclusão: As idades da toma de VASPR I e VASPR II poderão ter de ser alteradas por forma a adequarem-se às mudanças epidemiológicas ocorridas nos últimos anos em Portugal e contribuírem para a eliminação do sarampo no país.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil

INTRODUCTION: The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. METHODS: Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. RESULTS: A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. CONCLUSIONS: Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.

Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Short-and long-term effects of proallatotoxin (Ethoxyprecocene II) on Rhodnius prolixus females

Oogenesis and oviposition can be inhibited in female of Rhodnius prolixus by means of short-term experiment (first reproductive cycle) of a single dose of ethoxyprecocene II given by ingestion. The inhibition is dose-dependent as measured by oocyte growth, egg maturation and egg deposition. In a long-term experiment (second and third reproductive cycles) egg production and oogenesis can be partially or totally re-established by subsequent blood meals without ethoxyprecocene II. These findings suggest that in female R. prolixus, damage caused to corpus allatum by ethoxyprecocene II, in certain cases, is not irreversible.

Specific treatment of advanced Schistosomiasis liver disease in man: favourable results

One hundred eighty-four patients with hepatosplenic schistosomiasis mansoni from the northeast of Brazil were studied. All were treated with a single dose of Oxamniquine or Praziquantel, and were observed over 6 to 12 months. Special attention was given to the evolution of severe hepatopathy. Favourable results were obtained, particularly with the compensated hepatosplenic form. Hepatic function showed great improvement. Hepatomegaly and splenomegaly were significantly reduced in size, to a greater or lesser extent, in the great majority of patients. The implications of the results obtained are considered below.