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HIV type 1 subtype A envelope genetic evolution in a slow progressing individual with consistent broadly neutralizing antibodies
No full textStudies of viruses taken from individuals with broad cross-neutralizing antibodies against primary isolates may reveal novel antibody specificities and their associated epitopes that could be useful for immunogen design. We report on the Env antigenic variability of a slow progressing HIV-1 subtype A-infected donor with consistent broad cross-neutralizing antibodies during the second decade of disease progression after vertical transmission. The Env evolution is characterized by a genetic shift to variants with altered V1-V5 loop sequences, marked by consecutive changes in V1, V4-V5, and C3 and largely conserved V2 and V3 loop sequences. Major V1 Env sequence expansion, variation by a duplication event, and cumulative addition of cysteine residues and potential N-glycosylation sites over time may contribute to escape from antibody pressure directed to Env receptor domains by changing the exposure of neutralization-sensitive epitopes. Conservation of functional epitopes may correlate with the continued presence of broad cross-neutralizing antibodies
An analysis of the costs and treatment success of collaborative arrangements among public and private providers for tuberculosis control in Indonesia
No full textOBJECTIVES: To identify the cost-effectiveness of collaborative arrangements among public and private providers to employ the Directly Observed Treatment short-course (DOTS) strategy for tuberculosis (TB) control in Indonesia. METHODS: Three strategies were assessed: hospital out-patient diagnosis with referral to public health centres (PHCs) for treatment, hospital out-patient diagnosis and treatment, and private practitioner referral of suspects to PHCs. The outcome was the number of sputum smear positive TB cases successfully treated. Costs include direct costs to providers and patients. Uncertainty analysis was done for both costs and effectiveness data. RESULTS: The average cost per case successfully treated ranged from US567 for different strategies. The cost per additional case successfully treated incremental to existing TB programmes ranged from US982. In three of four provinces assessed, there was a clearly preferred strategy or strategies, although the preferred strategy differed by province; in one province a preferred strategy could not be identified. CONCLUSIONS: All strategies increased TB case finding, although attribution is tentative because of the study design. Neither collaboration among private practitioners nor among hospitals is clearly preferred based on cost-effectiveness. For hospitals, this study suggests that having hospitals refer patients to health centres is preferable over hospitals administering treatment
Thin-layer agar for detection of resistance to rifampicin, ofloxacin and kanamycin in Mycobacterium tuberculosis isolates
No full textBACKGROUND: In low-income countries there is a great need for economical methods for testing the susceptibility of Mycobacterium tuberculosis to antibiotics. OBJECTIVE: To evaluate the thin-layer agar (TLA) for rapid detection of resistance to rifampicin (RMP), ofloxacin (OFX) and kanamycin (KM) in M. tuberculosis clinical isolates and to determine the sensitivity, specificity and time to positivity compared to the gold standard method. METHODS: One hundred and forty-seven clinical isolates of M. tuberculosis were studied. For the TLA method, a quadrant Petri plate containing 7H11 agar with RMP, OFX and KM was used. Results were compared to the Bactec MGIT960 for RMP and the proportion method for OFX and KM. RESULTS: The sensitivity and specificity for RMP and OFX were 100% and for KM they were 100% and 98.7%, respectively. The use of a TLA quadrant plate enables the rapid detection of resistance to the three anti-tuberculosis drugs RMP, OFX and KM in a median of 10 days. CONCLUSION: TLA was an accurate method for the detection of resistance in the three drugs studied. This faster method is simple to perform, providing an alternative method when more sophisticated techniques are not available in low-resource settings
Simple data-reduction method for high-resolution LC-MS data in metabolomics
No full textMetabolomics LC-MS experiments yield large numbers of peaks, few of which can be identified by database matching. Many of the remaining peaks correspond to derivatives of identified peaks (e.g., isotope peaks, adducts, fragments and multiply charged molecules). In this article, we present a data-reduction approach that automatically identifies these derivative peaks. Results: Using data-driven clustering based on chromatographic peak shape correlation and intensity patterns across biological replicates, derivative peaks can be reliably identified. Using a test data set obtained from Leishmania donovani extracts, we achieved a 60% reduction of the number of peaks. After quality control filtering, almost 80% of the peaks could putatively be identified by database matching. Conclusion: Automated peak filtering substantially speeds up the data-interpretation process
Scaling up global social health protection: prerequisite reforms to the International Monetary Fund
No full textPeople living in low-income countries require protection from the economic and social impacts of global economic competition, yet, historically, the International Monetary Fund's (IMF) fiscal austerity programs have weakened the potential for redistribution both within poor countries and between rich and poor countries. The current development paradigm's focus on "sustainability" is an obstacle to developing systems of global social protection and an impediment to future progress. Reforming IMF policy conditionality and democratizing the IMF's decision-making processes will be necessary for offsetting growing inequalities in health financing among poor nations
Rapid detection of resistant tuberculosis by nitrate reductase assay performed in three settings in Brazil
No full textOBJECTIVES: To evaluate nitrate reductase assay (NRA) efficacy for streptomycin, isoniazid, rifampicin and ethambutol susceptibility testing of Mycobacterium tuberculosis strains. METHODS: Results were generated by three laboratories: the Instituto Adolfo Lutz (IAL) Mycobacteria Reference Laboratory and two IAL Regional Laboratories in Santo André and Sorocaba, São Paulo State, Brazil. One hundred and twenty M. tuberculosis strains were simultaneously tested using NRA and the proportion method (PM), while 117 strains were tested using both NRA and BACTEC MGIT 960 (M960). RESULTS: Repeatability analysis of NRA results showed rates of 100% for isoniazid and ethambutol and 97% for streptomycin and rifampicin susceptibility detection, representing substantial agreement. McNemar testing of the data also indicates that NRA and PM, as well as NRA and M960, do not differ significantly. On average, NRA results were available after 10 days. CONCLUSIONS: The data demonstrate that NRA is reliable for susceptibility testing of isoniazid and rifampicin, the two most important drugs for the treatment of tuberculosis. In addition, the reduction in the time necessary to obtain susceptibility results is of fundamental importance
Availability of free fruits and vegetables at canteen lunch improves lunch and daily nutritional profiles: a randomised controlled trail
No full textCanteens are known to be promising settings for activities to promote intake of fruits and vegetables, but it remains unclear to what extent distributing free fruits and vegetables can influence dietary patterns of customers. The present study evaluated the effect of providing fruits and vegetables for free in a university canteen on the daily diet of university canteen customers. Canteen customers (n 209) were randomly allocated to a fruit and vegetable group (FVG) and a control group (CG). FVG participants were given two portions of fruits and one portion of vegetables for free at lunchtime. Food and beverage intake was measured using a dietary record for 3 d and dietary quality was appraised using a comprehensive scoring system. The FVG participants ate 80 g more fruits (P < 0.01) and 108 g more vegetables (P < 0.001) on a daily basis compared with the CG participants. No differences were found for energy density, total energy, Na and energy from fat between the groups per day. A higher intake of fruits and vegetables was observed at lunch and of vegetables during the dinner and evening snacks. The FVG participants were more likely to comply with dietary recommendations for fruits and vegetables and had a better dietary profile on the study days and for the lunch consumed on those days. The results of the present study demonstrate how modifications of a canteen lunch can be instrumental to enhance the nutritional quality of lunch as well as the overall quality of the diet of the customers
Development and validation of a multiplex real-time PCR assay for simultaneous genotyping and human T-lymphotropic virus type 1, 2, and 3 proviral load determination
No full textThe human T-lymphotropic virus (HTLV) proviral load remains the best surrogate marker for disease progression. Real-time PCR techniques have been developed for detection and quantification of cosmopolitan HTLV type 1a (HTLV-1a) and HTLV-2. Since a growing level of diversity in subtypes and genotypes is observed, we developed a multiplex quantitative PCR for simultaneous detection, genotyping, and quantification of proviral loads of HTLV-1, 2, and 3. Our assay uses tax type-specific primers and dually labeled probes and has a dynamic range of 10(5) to 10 HTLV copies. One hundred sixty-three samples were analyzed, among which all of the different subtypes within each HTLV genotype could be detected. The performance of proviral load determination of our multiplex assay was compared with that of a previously published HTLV-1 singleplex quantitative PCR based on SYBR green detection, developed at a different institute. Linear regression analysis showed a statistically significant (P < 0.0001) and strong (r(2) = 0.87) correlation between proviral load values measured with the two distinct real-time PCR assays. In conclusion, our novel assay offers an accurate molecular diagnosis and genotyping, together with the determination of the proviral load of HTLV-infected individuals, in a single amplification reaction. Moreover, our molecular assay could offer an alternative when current available serological assays are insufficient