High frequency of resistance to the drugs isoniazid and rifampicin among tuberculosis cases in the city of Cabo de Santo Agostinho, an urban area in Northeastern Brazil

The objective of the present study was to investigate the frequency and risk factors for developing multidrug-resistant tuberculosis in Cabo de Santo Agostinho, PE. This was a prospective study conducted from 2000 to 2003, in which suspected cases were investigated using bacilloscopy and culturing. Out of 232 confirmed cases of tuberculosis, culturing and antibiotic susceptibility tests were performed on 174. Thirty-five of the 174 cultures showed resistance to all drugs. The frequencies of primary and acquired resistance to any drug were 14% and 50% respectively, while the frequencies of primary and acquired multidrug resistance were 8.3% and 40%. Previous tuberculosis treatment and abandonment of treatment were risk factors for drug resistance. The high levels of primary and acquired resistance to the combination of isoniazid and rifampicin contributed towards the difficulties in controlling tuberculosis transmission in the city.

Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo

INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.

Evaluation of constitutive and inducible resistance to clindamycin in clinical samples of Staphylococcus aureus from a tertiary hospital

IntroductionInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become common in hospitals and the community environment, and this wide resistance has limited patient treatment. Clindamycin (CL) represents an important alternative therapy for infections caused by S. aureus. Antimicrobial susceptibility testing using standard methods may not detect inducible CL resistance. This study was performed to detect the phenotypes of resistance to macrolides-lincosamides-streptogramin B (MLSB) antibiotics, including CL, in clinical samples of S. aureusfrom patients at a tertiary hospital in Santa Maria, State of Rio Grande do Sul, Brazil.MethodsOne hundred and forty clinical isolates were submitted to the disk diffusion induction test (D-test) with an erythromycin (ER) disk positioned at a distance of 20mm from a CL disk. The results were interpreted according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI).ResultsIn this study, 29 (20.7%) of the 140 S. aureus samples were resistant to methicillin (MRSA), and 111 (79.3%) were susceptible to methicillin (MSSA). The constitutive resistance phenotype (cMLSB) was observed in 20 (14.3%) MRSA samples and in 5 (3.6%) MSSA samples, whereas the inducible resistance phenotype (iMLSB) was observed in 3 (2.1%) MRSA samples and in 8 (5.8%) MSSA samples.ConclusionsThe D-test is essential for detecting the iMLSBphenotype because the early identification of this phenotype allows clinicians to choose an appropriate treatment for patients. Furthermore, this test is simple, easy to perform and inexpensive.

Role Of MMP-2 and MMP-9 in Resistance to Drug Therapy in Patients with Resistant Hypertension

AbstractBackground:Despite the increased evidence of the important role of matrix metalloproteinases (MMP-9 and MMP‑2) in the pathophysiology of hypertension, the profile of these molecules in resistant hypertension (RHTN) remains unknown.Objectives:To compare the plasma levels of MMP-9 and MMP-2 and of their tissue inhibitors (TIMP-1 and TIMP-2, respectively), as well as their MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, between patients with controlled RHTN (CRHTN, n=41) and uncontrolled RHTN (UCRHTN, n=35). In addition, the association of those parameters with clinical characteristics, office blood pressure (BP) and arterial stiffness (determined by pulse wave velocity) was evaluate in those subgroups.Methods:This study included 76 individuals diagnosed with RHTN and submitted to physical examination, electrocardiogram, and laboratory tests to assess biochemical parameters.Results:Similar values of MMP-9, MMP-2, TIMP-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were found in the UCRHTN and CRHTN subgroups (P>0.05). A significant correlation was found between diastolic BP (DBP) and MMP-9/TIMP-1 ratio (r=0.37; P=0.02) and DPB and MMP-2 (r=-0.40; P=0.02) in the UCRHTN subgroup. On the other hand, no correlation was observed in the CRHTN subgroup. Logistic regression models demonstrated that MMP-9, MMP-2, TIMP-1, TIMP-2 and their ratios were not associated with the lack of BP control.Conclusion:These findings suggest that neither MMP-2 nor MMP-9 affect BP control in RHTN subjects.

Development of cell mediated immunity to flagellar antigens and acquired resistance to infection by Trypanosoma cruzi in mice

Modulation by BCG and/or cyclophosphamide of sensitization of mice with flagellar fraction (a tubulin-enriched fraction) prevented death of mice challenged with T. cruzi CL strain trypomastigotes recovered from Vero cells. A methodology was ceveloped to assay specific antigens and to determine optimal doses for sensitization and elicitation of DTH in mice. CL strain is predominantly myotropic strain which does not produce important parasitism of mononuclear phagocyte cells; these cells appear to control infection when activated in vivo. Maximum protection was seen in this study when BCG and cyclophosphamide were associated, but protection was observed also when cyclophosphamide, that prevents supressor T cells, was applied 2 days before flagellar fraction sensitization in normal mice. These experiments suggested that the macrophage may have an important role in the early phases of infection particularly when nonspecific stimulation is associated with specific sensitization. A correlation betwen delayed hypersensitivity to parasite antigens and protection was observed.

Anti-schistosomal drugs: observations on the mechanism of drug resistance to hycanthone, and on the involvement of host antibodies in the mode of action of praziquantel

This paper reports recent observations from our laboratory dealing with the anti-schistosome drugs hycanthone (HC) and praziquantel (PZQ). In particular, we discuss a laboratory model of drug resistance to HC in Schistosoma mansoni and show that drug sensitive and resistant lines of the parasite can be differentiated on the basis of restriction fragment length polymorphisms using homologous ribosomal gene probes. In addition, we summarize data demonstrating that effective chemotherapy of S. mansoni infection with PZQ in mice requires the presence of host anti-parasite antibodies. These antibodies bind to PZQ treated worms and may be involved in an antibody-dependent cellular cytotoxicity reactions which result in the clearance of worms from the vasculature.

Methods for field detection of resistance to temephos in simuliids. Larval esterase level and topical application of the insecticide to adults

Two practical field methods for indirect detection of simuliid populations resistant to temephos are proposed. The first is based on high esterase activity in resistant larvae and involves adaptations of a filter paper test in which faintly stained spots indicate susceptible populations and strongly stained ones reveal populations resistant to temephos. The second is based on the resistance to the larvicide when adults are topically exposed, and involves the use of diagnostic doses obtained by the comparison between the LD50 for susceptible and resistant populations. The relevance of such methods is discussed in order to help resistance detection in Simulium pertinax Kollar control programmes.

Human IgE responses to Schistosoma mansoni and resistance to reinfection

Schistosoma mansoni infected Kenyan patients were treated and the intensities of their reinfections were followed over the next two years. in addition, their pre- and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for schistosoma, egg and adult worm, were measured in ELISA. No reinfection took place before six months post-treatment. Reinfection intensities varied with age; the younger children becoming reinfected at significantly higher intensities than older individuals. When antibody and reinfection levels were compared, only the six month post-treatment IgE response against adult worm correlated negatively with intensities of reinfection and, therefore, was predictive of resistance or immunity to reinfection. IgE and IgG specific Western Blots were carried out. The adult worm antigens recognized by IgE were restricted compared with the IgG responses of the same patients, although no individual antigen was uniquely recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most but not all high IgE responders. Patients with IgE responses against this antigen suffered significantly lower subsequent levels of reinfection, compared with non-responders. A monospecific rabbit antiserum against the 22KDa adult worm antigen showed that this antigen is specifically located in the tegument of the adult worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early 'skin' schistosomula. It is possible that this antigen is a target for human IgE mediated immune effector mechanisms active against the post skin stage schistosomula and that this is boosted by the death of adult worms.

Comparative Histopathology of Biomphalaria glabrata, B. tenagophila and B. straminea with Variable Degrees of Resistance to Schistosoma mansoni Miracidia

A comparative histopathological study of three snails species - Biomphalaria glabrata, B. tenagophila and B. straminea - which had been infected with Schistosoma mansoni miracidia revealed similar qualitative features, consisting of areas of sporocyst proliferation and differentiation associated with reactive host reaction, at the time they were actively eliminating great number of cercariae. However, in specimens that were exposed to miracidia but failed to eliminate cercariae later on, different histopathological pictures were observed in different snail species. While B. glabrata exhibited frequent focal (granulomatous) proliferation of amebocytes in several organs, B. tenagophila and B. straminea only rarely showed such reactive changes, suggesting that the mechanism of resistance to miracidial infection probably follows different pathways in the snail species studied

Resistance to Starvation of Triatoma rubrofasciata (De Geer, 1773) under Laboratory Conditions (Hemiptera: Reduviidae: Triatominae)

The present work aims at learning the period of resistance to starvation (molting/death) of Triatoma rubrofasciata in different stages of development and the respective loss of weight until death. Eggs of specimens from the greater area of the city of São Luis in the State of Maranhão, Brazil, yielded approximately 300 nymphs. These nymphs were placed in labelled Borrel glasses, in which they were weekly fed on rats (Rattus norvegicus), until reaching the stage to be observed. The experiments were conducted in a climatic chamber regulated at 29 ± 1° C, 70% relative humidity and 12 hr photoperiod. The resistance to starvation increased according to the stage of development, except for adult bugs, whose results were similar to the 3rd stage nymphs. In all these development stages there was an abrupt loss of weight in the first week, followed by a gradual loss until death. Comparing this work with those of other authors, it was observed that T. rubrofasciata is among the less resistant triatomine species.

Resistance to starvation of Rhodnius neivai Lent, 1953 (Hemiptera: Reduviidae: Triatominae) under experimental conditions

The period of resistance to starvation and the loss of weight until death of Rhodnius neivai in all stages of development were studied. Work was based on experiments conducted under controlled laboratory conditions. One hundred specimens of each nymphal instar were observed: 50 were fed on chicken and 50 on rabbit. Adult females and males were kept together and fed on each host. All bugs were weighed weekly until death. Laid eggs were collected weekly and observed during five weeks to obtain hatchability. Resistance to starvation was similar with both hosts and increased with the evolutionary stage, excepting the 5th nymphal instar and adults. With both hosts, loss of weight was abrupt in the first week and steady in the following weeks. In adults, on the first weeks after eating, there was little or no mortality, after which mortality increased rapidly with the starving time. Reproductive output was higher in the bugs fed on rabbit. R. neivai is among the least resistant triatomine species.