Assessment of chloroquine single dose treatment of malaria due to Plasmodium vivax in Brazilian Amazon

Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment. In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg, the authors realized a double-blind, placebo-controlled trial in 132 outpatients with vivax malaria. Patients were distributed into two groups: group CPLA, given chloroquine 600 mg (single dose) on the first day of treatment, and two doses of placebo on second and third days. Group CHLO, given chloroquine 600 mg on first day and 450 mg on second and third day. Geometric means of the parasite density during the follow-up was similar in both groups. No differences were observed in the parasitological cure between the two groups (p = 0.442). There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine. This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region, nevertheless the inadequate response of three patients indicates the need for further studies.

Electromyography function, disability degree, and pain in leprosy patients undergoing neural mobilization treatment

INTRODUCTION: This study aimed to evaluate the effect of the neural mobilization technique on electromyography function, disability degree, and pain in patients with leprosy. METHODS: A sample of 56 individuals with leprosy was randomized into an experimental group, composed of 29 individuals undergoing treatment with neural mobilization, and a control group of 27 individuals who underwent conventional treatment. In both groups, the lesions in the lower limbs were treated. In the treatment with neural mobilization, the procedure used was mobilization of the lumbosacral roots and sciatic nerve biased to the peroneal nerve that innervates the anterior tibial muscle, which was evaluated in the electromyography. RESULTS: Analysis of the electromyography function showed a significant increase (p<0.05) in the experimental group in both the right (Δ%=22.1, p=0.013) and the left anterior tibial muscles (Δ%=27.7, p=0.009), compared with the control group pre- and post-test. Analysis of the strength both in the movement of horizontal extension (Δ%right=11.7, p=0.003/Δ%left=27.4, p=0.002) and in the movement of back flexion (Δ%right=31.1; p=0.000/Δ%left=34.7, p=0.000) showed a significant increase (p<0.05) in both the right and the left segments when comparing the experimental group pre- and post-test. The experimental group showed a significant reduction (p=0.000) in pain perception and disability degree when the pre- and post-test were compared and when compared with the control group in the post-test. CONCLUSIONS: Leprosy patients undergoing the technique of neural mobilization had an improvement in electromyography function and muscle strength, reducing disability degree and pain.

Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients

INTRODUCTION: In Brazil there is a large area of overlap of visceral leishmaniasis (VL) and HIV infection, which favored a increased incidence of coinfection Leishmania/HIV. METHODS: This study evaluated 65 consecutive patients with VL and their clinical response to treatment in two health care settings in Belo Horizonte, Brazil. RESULTS: At baseline, the clinical picture was similar between both groups, although diarrhea and peripheral lymphadenomegaly were more frequent in HIV-infected subjects. HIV-positive patients had lower median blood lymphocyte counts (686/mm³ versus 948/mm³p = 0.004) and lower values of alanine aminotransferase (ALT) (48IU/L versus 75.6IU/L p = 0.016) than HIV-negative patients. HIV-positive status (hazard ratio = 0.423, p = 0.023) and anemia (HR = 0.205, p = 0.002) were independent negative predictors of complete clinical response following antileishmanial treatment initiation. CONCLUSIONS: This study reinforces that all patients with VL should be tested for HIV infection, regardless of their clinical picture. This practice would allow early recognition of coinfection with initiation of antiretroviral therapy and, possibly, reduction in treatment failure.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Conization, frozen section examination, and planned hysterectomy in the treatment of high-grade cervical intraepithelial neoplasia

PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64%) had positive cone margins and 9 (36%) had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%). Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.

Clinical Coronary In-Stent Restenosis Follow-Up after Treatment and Analyses of Clinical Outcomes

Background: Clinical in-stent restenosis (CISR) is the main limitation of coronary angioplasty with stent implantation. Objective: Describe the clinical and angiographic characteristics of CISR and the outcomes over a minimum follow-up of 12 months after its diagnosis and treatment. Methods: We analyzed in 110 consecutive patients with CISR the clinical presentation, angiographic characteristics, treatment and combined primary outcomes (cardiovascular death, nonfatal acute myocardial infarction [AMI]) and combined secondary (unstable angina with hospitalization, target vessel revascularization and target lesion revascularization) during a minimal follow-up of one year. Results: Mean age was 61 ± 11 years (68.2% males). Clinical presentations included acute coronary syndrome (ACS) in 62.7% and proliferative ISR in 34.5%. CISR was treated with implantation of drug-eluting stents (DES) in 36.4%, Bare Metal Stent (BMS) in 23.6%, myocardial revascularization surgery in 18.2%, balloon angioplasty in 15.5% and clinical treatment in 6.4%. During a median follow-up of 19.7 months, the primary outcome occurred in 18 patients, including 6 (5.5%) deaths and 13 (11.8%) AMI events. Twenty-four patients presented a secondary outcome. Predictors of the primary outcome were CISR with DES (HR = 4.36 [1.44–12.85]; p = 0.009) and clinical treatment for CISR (HR = 10.66 [2.53–44.87]; p = 0.001). Treatment of CISR with BMS (HR = 4.08 [1.75–9.48]; p = 0.001) and clinical therapy (HR = 6.29 [1.35–29.38]; p = 0.019) emerged as predictors of a secondary outcome. Conclusion: Patients with CISR present in most cases with ACS and with a high frequency of adverse events during a medium-term follow-up.

The effectiveness of tipi in the treatment of hip and knee osteoarthritis: a preliminary report

Osteoarthritis (OA) is a common painful inflammatory condition occurring mainly in the later half of life. Hipe and knee are the joints mostly affected. Petiveria alliacea (tipi) popularly known as an anti-rheumatic medicine, has been used by OA patients to relief pain. This one-week cross-over double-blind trial has preliminary evaluated the analgesic effect of tipi tea in 14 patients with hip and knee OA. Imperata exaltata (sape) was used as the Placebo tea. The pain assessments that were made at baseline and before the start of the second treatment period by treatment groups were comparable. While taking tipi or placebo tea patients experienced a statistically significant improvement in pain on motion and pain at night. The comparison between the improvements reported while on tipi and placebo tea, however, did not disclose any statistically significant difference. At the conclusion of the study 7 patients preferred tipi tea and 6 preferred placebo tea (NS). Two patients reported insomnia, one durign placebo treatment and the other during tipi treatment. In this preliminary report both teas succeeded in the aim of relieving pain.

Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and control of malaria

With the use of a simple formulary, field by health agents was ewstablished a monitoring programme for responses of P. falciparum to the antimalarial drugs. This monitoring programme is emphasized for knowledge of the epidemiology of the drug resistance and the control of malaria falciparum in Amazonan Basin where occurs more than 95% of Brazilian malaria cases every year. It was demonstrated that still now 4-aminoquinolines have a great importance for the mortality control in areas where just SUCAM (National Health Foundation - Health Ministry) agenst are present without any medical assistance. The results obtained permitted the simplification of malaria treatment in Brazil Important conclusions were established in the field of malaria drug resistance.

Therapeutic failure of praziquantel in the treatment of Schistosoma haematobium infection in Brazilians returning from Africa

Several cases of therapeutic failure of praziquantel used for the treatment of urinary schistosomiasis have been reported. Alternative drugs, like niridazol and metrifonate, have shown a lower therapeutic effect and more side effects than praziquantel. Twenty-six Brazilian military men (median age of 29 years) with a positive urine parasitological exam who were part of a United Nation peace mission in Mozambique in 1994 were treated with 40 mg/kg body weight praziquantel, single dose. They swimmed in Licungo river (Mocuba city, Mozambique) during the weekends. After this, they presented haematuria, dysuria, polakiuria, and lumbar pain. Control cystoscopy examinations carried out between 6 and 24 months after each treatment (including two additional treatments at a minimum interval of 6 months) revealed the presence of viable eggs. Granulomas in the vesical submucosa were observed in 46.2% (12/26) of the individuals. A vesical biopsy confirmed the presence of granulomas in all of these patients and the presence of viable eggs in 34.3% (9/26) of individuals who no longer excreted eggs in urine. The eggs filled with miracidia showed characteristics of viability. Histopathological examination using different strains demonstrated therapeutic failure and the need for repeated treatment. In this study, we demonstrated a low efficacy of praziquantel in the treatment of schistosomiasis haematobia, and the necessity of the urinary bladder biopsy as criterion of cure.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per µl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Long-term outcomes of school-based treatment for control of urinary schistosomiasis: a review of experience in Coast Province, Kenya

Urinary schistosomiasis remains a significant burden for Africa and the Middle East. The success of population-based control programs will depend on their impact, over many years, on Schistosoma haematobium reinfection and associated disease. In a multi-year (1984-1992) control program in Kenya, we examined risk for S. haematobium reinfection and late disease during and after annual school-based treatment. In this setting, long-term risk of new infection was independently associated with location, age, hematuria, and incomplete treatment, but not with sex or frequency of water contact. Thus, very local environmental features and age-related factors played an important role in S. haematobium transmission, such that population-based control programs should optimally tailor their efforts to local conditions on a village-by-village basis. In 2001-2002, the late benefits of earlier participation in school-based antischistosomal therapy were estimated in a cohort of formerly-treated adult residents compared to never-treated adults from the same villages. Among age-matched subjects, current infection prevalence was lower among those who had received remote therapy. In addition, prevalence of bladder abnormality was lower in the treated group, who were free of severe bladder disease. Treatment of affected adults resulted in rapid resolution of infection and any detectable bladder abnormalities. We conclude that continued treatment into adulthood, as well as efforts at long-term prevention of infection (transmission control) are necessary to achieve optimal morbidity control in affected communities.

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Cardiac damage is a frequent manifestation of Chagas disease, which is caused by the parasite Trypanosoma cruzi. Selenium (Se) is an essential micronutrient, the deficiency of which has been implicated in the development of cardiomyopathy. Our group has previously demonstrated that Se supplementation prevents myocardial damage during acute T. cruzi infection in mice. In this study, we analyzed the effect of Se treatment in cases of T. cruzi infection using prevention and reversion schemes. In the Se prevention scheme, mice were given Se supplements (2 ppm) starting two weeks prior to inoculation with T. cruzi(Brazil strain) and continuing until 120 days post-infection (dpi). In the Se reversion scheme, mice were treated with Se (4 ppm) for 100 days, starting at 160 dpi. Dilatation of the right ventricle was observed in the infected control group at both phases of T. cruzi infection, but it was not observed in the infected group that received Se treatment. Surviving infected mice that were submitted to the Se reversion scheme presented normal P wave values and reduced inflammation of the pericardium. These data indicate that Se treatment prevents right ventricular chamber increase and thus can be proposed as an adjuvant therapy for cardiac alterations already established by T. cruziinfection.

Profile of total IgG, IgG1, IgG2, IgG3 and IgG4 levels in sera of patients with paracoccidioidomycosis: treatment follow-up using Mexo and rPb27 as antigens in an ELISA

The levels of total of IgG, IgG1, IgG2, IgG3 and IgG4 were evaluated in 54 patients with chronic paracoccidioidomycosis (PCM) before, during and after treatment using an enzyme-linked immunosorbent assay with Mexo and recombinant Pb27 (rPb27) as the antigens. Mexo was effective in distinguishing PCM patients from individuals in the negative control group (NC) based on total IgG and rPb27 performed worse than Mexo when these two groups were compared. IgG1, IgG2, IgG3 and IgG4 could not be used to clearly distinguish PCM patients from those in the NC group using either antigen. There was no clear relationship between antibody levels and the period of treatment. The majority of patients presented with decreased antibody levels during treatment, with no statistically significant differences among the different periods of treatment. Only IgG4 presented a negative correlation between its levels and clinical improvement during treatment. In total, 65% of untreated PCM patients showed reactivity against IgG4 when the Mexo antigen was used and this reactivity decreased over the course of treatment. There was a tendency towards decreasing antibody levels during treatment, but these antibody levels did not necessarily clear after the treatment was stopped. Mexo was useful for PCM diagnosis using total IgG; however, more studies are necessary before this antigen can be used in measuring the levels of total IgG and its subclasses for monitoring patients during treatment.

Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4%) had cirrhosis and HCV genotype 1 predominated (64.3%). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients

Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.