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Adaptations in the glucose metabolism of procyclic Trypanosoma brucei isolates from tsetse flies and during differentiation of bloodstream forms
No full textProcyclic forms of Trypanosoma brucei isolated from the midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete Krebs cycle. Furthermore, short stumpy bloodstream forms produce acetate and are apparently metabolically preadapted to adequate functioning in the tsetse fly
Integrated health care networks in Latin America: toward a conceptual framework for analysis
No full textEscherichia coli O157 prevalence in different cattle farm types and identification of potential risk factors
No full textAlthough the prevalence of Escherichia coli O157 on cattle farms has been examined extensively, the relationship between this pathogen and farm type has been established only rarely. A large-scale study was designed to determine the prevalence of E. coli O157 in the Flemish region of Belgium on farms of dairy cattle, beef cattle, mixed dairy and beef cattle, and veal calves. The effect of various factors on the occurrence at the pen level also was evaluated. In 2007, 180 farms were randomly selected based on region, farm size, and number of animals purchased and were examined using the overshoe sampling method. When possible, overshoes used in areas containing animals in three different age categories ( 30 months) were sampled on each farm. In total, 820 different pens were sampled and analyzed for the presence of E. coli O157 by enrichment, immunomagnetic separation, and plating on selective agar. Presumptive E. coli O157 colonies were identified using a multiplex PCR assay for the presence of the rfb(O157) and fliC(H7) genes. The statistical analysis was carried out with Stata SE/10.0 using a generalized linear regression model with a logit link function and a binomial error distribution. The overall farm prevalence of E. coli O157 was 37.8% (68 of 180 farms). The highest prevalence was found on dairy cattle farms (61.2%, 30 of 49 farms). The prevalences on beef, mixed dairy and beef, and veal calf farms were 22.7% (17 of 75 farms), 44.4% (20 of 45 farms), and 9.1% (1 of 11 farms), respectively. A significant positive correlation between age category and E. coli O157 prevalence was found only on mixed dairy and beef farms and dairy farms. No influence of farm size or introduction of new animals was demonstrated
Prevalence and antimicrobial resistance of Salmonella isolated from broiler farms, chicken carcasses, and street-vended restaurants in Casamance, Senegal
No full textThis study was undertaken to determine the prevalence and distribution of Salmonella on 57 randomly selected broiler farms at the end of the rearing period and in chicken products in urban and periurban areas in Casamance, Senegal, and to evaluate the antimicrobial resistance profiles of the Salmonella serovars. Salmonella was detected in chicken feces, on carcass skin, and in muscle on 35.1, 38.6, and 29.8% of farms, respectively. Salmonella was found in chicken meat servings from 14.3% of the 42 street restaurants and in 40.4% of the 285 chicken carcasses examined. The prevalence on skin and in muscle was significantly associated with the detection of Salmonella in feces (P <or= 0.001). Eighteen Salmonella serovars were identified; the most common were Brancaster (57.9%), Goelzau (10.7%), Kentucky (8.4%), and Hadar (7.3%). High levels of resistance were found to trimethoprim-sulfamethoxazole, tetracycline, trimethoprim, streptomycin, and sulfonamides. All Salmonella serovars were susceptible to fluoroquinolones and third-generation cephalosporins. A large proportion of the isolates belonging to 11 serovars were resistant to two or more antibiotics. Salmonella continues to be of serious concern in the broiler production chain in Senegal
Progress in the development of piperaquine combinations for the treatment of malaria
No full textPURPOSE OF REVIEW: Dihydroartemisinin-piperaquine is a new and extremely promising artemisinin-containing fixed-combination antimalarial, about to be registered with international regulatory authorities such as the European Medicines Agency. A formulation produced according to good manufacturing practices should be available soon. RECENT FINDINGS: Piperaquine is characterized by a slow absorption, long mean terminal elimination half-life and large mean volume distribution. However, children, compared to the population mean profile, tend to have a smaller central volume of distribution, a shorter distribution half-life and a more rapid fall in early piperaquine plasma concentrations, suggesting that an increase of the weight-adjusted dosage in children may be required. In addition, the oral bioavailability of piperaquine improves when given with a high-fat meal, though this does not necessarily translate into a higher efficacy. Several clinical trials have repeatedly shown that dihydroartemisinin-piperaquine is well tolerated and efficacious, with the only exception of one trial recently carried out in Papua New Guinea. Patients treated with dihydroartemisinin-piperaquine may have a higher rate of person-gametocyte-weeks, though it is unclear whether this translates into a higher infectiousness to biting anophelines. SUMMARY: The dosage recommended for children may need to be reviewed and the usefulness of the coadministration with food should be determined. Establishing safety and efficacy of this treatment in pregnancy remains a priority
In vitro sensitivity testing of Leishmania clinical field isolates: preconditioning of promastigotes enhances infectivity for macrophage host cells
No full textDiagnostic material from patients with leishmaniasis is generally available as promastigotes, and proper testing for susceptibility to first-line drugs by the intracellular amastigote assay is frequently hampered by the poor infectivity of the promastigotes for the macrophage host cell. Several conditions for optimization of the in vitro metacyclogenesis and cell infectivity of Leishmania donovani, L. guyanensis, and L. braziliensis field strains obtained from patients receiving standard antimony medication were investigated. Triggering log-phase promastigotes to become amastigote-like by increasing the temperature or acidifying the culture medium was not successful. Adequate metacyclogenesis and the highest levels of macrophage infection were obtained after 5-day-old late-log-phase promastigote cultures were preconditioned at 25 degrees C to pH 5.4 for 24 h in Schneider's medium prior to infection. The susceptibility assay with primary peritoneal mouse macrophages included pentavalent antimony (Sb(V); sodium stibogluconate), trivalent antimony (Sb(III); potassium antimonyl tartrate), miltefosine, and the experimental drug PX-6518. All strains were sensitive to miltefosine (50% inhibitory concentration [IC(50)] < 10 microM) and PX-6518 (IC(50) < 2 microg/ml) but showed distinct susceptibility to Sb(V) and/or Sb(III), depending on whether they were derived from cured, relapse, or nonresponder patients. Within the available set of Leishmania species and strains, simultaneous Sb(V)-Sb(III) resistance was clearly associated with treatment failure; however, a larger set of isolates is still needed to judge the predictive value of Sb(V)-Sb(III) susceptibility profiling on treatment outcome. In conclusion, the proposed conditioning protocol further contributes toward a more standardized laboratory model for evaluation of the drug sensitivities of field isolates
Mycobacterium tuberculosis strains with highly discordant rifampin susceptibility test results
No full textThe objectives of this study were to investigate the origin of highly discordant rifampin (rifampicin) (RMP) drug susceptibility test results obtained for Mycobacterium tuberculosis strains during proficiency testing. Nine Supra-National Tuberculosis Reference Laboratories tested the RMP susceptibilities of 19 selected M. tuberculosis strains, using standard culture-based methods. The strains were classified as definitely resistant (R) (n = 6) or susceptible (S) (n = 2) or probably resistant (PR) (n = 8) or susceptible (PS) (n = 3) based on rpoB mutations and treatment outcome. All methods yielded a susceptible result for the two S and three PS strains lacking an rpoB mutation and a resistant result for one R strain with a Ser531Leu mutation and one PR strain with a double mutation. Although the remaining 12 R and PR strains had rpoB mutations (four Asp516Tyr, three Leu511Pro, two Leu533Pro, one each His526Leu/Ser, and one Ile572Phe), they were all susceptible by the radiometric Bactec 460TB or Bactec 960 MGIT methods. In contrast, only one was susceptible by the proportion method on Löwenstein-Jensen medium and two on Middlebrook 7H10 agar. Low-level but probably clinically relevant RMP resistance linked to specific rpoB mutations is easily missed by standard growth-based methods, particularly the automated broth-based systems. Further studies are required to confirm these findings, to determine the frequency of these low-level-resistant isolates, and to identify technical improvements that may identify such strains
Public-sector ART in the Free State Province, South Africa: community support as an important determinant of outcome
No full textThe treatment outcomes for large-scale public antiretroviral therapy (ART) programs in developing countries, although promising, are still preliminary. The scaling-up of ART in resource-limited settings is inevitably hampered by human resource shortages. Therefore, community support for ART patients may play an important role in achieving favorable treatment outcomes. This study aimed to extend the current literature by investigating how immunological and virological responses to ART, measured at three points in time (after six, 12, and 24 months of ART), are influenced by patient characteristics (age, sex), health literacy (educational level and knowledge about HIV/AIDS), baseline CD4 cell count, baseline viral load, and three forms of community support (treatment buddy, community health worker [CHW], and HIV/AIDS support group). Cross-lagged regression analysis was used to test these relationships in a sample of 268 patients enrolled in the public-sector ART program of the Free State Province of South Africa (2004-2007). After 24 months of ART, 76.4% of patients were classified as treatment successes (viral load or = 200 cells/microL), compared with 64.1% at 12 months and 46.1% at six months. When we examined the predictors of ART success, baseline health and all three community support initiatives had a positive effect on ART outcomes after six months, whereas patient characteristics had little effect. Six months later, patients with the support of a treatment buddy, CHW, or support group had better ART outcomes, whereas the impact of baseline health had diminished. After two years of treatment, community support again emerged as the most important predictor of treatment success. This study confirms that the ART provided by South African public-sector health services is effective. These results provide evidence from the field that communities can be mobilized to sustain these favorable outcomes under conditions of limited human resources for healthcare
Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies
No full textBACKGROUND: A minority of HIV-1 infected individuals develop broad cross-neutralizing (BCN) plasma antibodies that are capable of neutralizing a spectrum of virus variants belonging to different HIV-1 clades. The aim of this study was to identify the targeted epitopes of an individual with BCN plasma antibodies, referred to as ITM4, using peptide phage display. This study also aimed to use the selected mimotopes as tools to unravel the evolution of the antibody landscape and the viral envelope escape which may provide us with new insights for vaccine design. RESULTS: This study led us to identify ITM4 plasma antibodies directed to the 4E10 epitope located in the gp41 membrane-proximal external region (MPER). Analysis of antibody specificities revealed unusual immunogenic properties of the ITM4 viral envelope, as not only the V3 loop and the gp41 MPER but also the C1 and lentivirus lytic peptide 2 (LLP2) region seem to be targets of the immune system. The 4E10-like antibodies are consistently elicited during the 6-year follow up period. HIV-1 ITM4 pseudoviruses showed an increasing resistance over time to MPER monoclonal antibodies 4E10 and 2F5, although no changes are found in the critical positions of the epitope. Neutralization of COT6.15 (subtype C; 4E10-sensitive) pseudoviruses with alanine substitutions in the MPER region indicated an overlapping specificity of the 4E10 monoclonal antibody and the ITM4 follow up plasma. Moreover the 4E10-like antibodies of ITM4 contribute to the BCN capacity of the plasma. CONCLUSIONS: Using ITM4 BCN plasma and peptide phage display technology, we have identified a patient with 4E10-like BCN antibodies. Our results indicate that the elicited 4E10-like antibodies play a role in virus neutralization. The viral RNA was isolated at different time points and the ITM4 envelope sequence analysis of both early (4E10-sensitive) and late (4E10-resistant) viruses suggest that other regions in the envelope, outside the MPER region, contribute to the accessibility and sensitivity of the 4E10 epitope. Including ITM4 specific HIV-1 Env properties in vaccine strategies may be a promising approach
