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Evaluation of a flow cytometry method for CD4 T cell enumeration based on volumetric primary CD4 gating using thermoresistant reagents
No full textLaboratory follow-up of HIV patients in resource-limited settings requires appropriate instruments for CD4 T cell enumeration. In this study, we evaluated the application of a simplified, mobile and robust flow cytometry system, the Apogee Auto 40 analyzer (Auto40) using thermoresistant reagents, for CD4 T cell enumeration. We measured the absolute CD4 counts in fresh whole blood samples from 170 Senegalese subjects, including 129 HIV-positive (HIV+) patients and 41 HIV-negative (HIV-) controls. Based on volumetric primary CD4 gating, cells were stained with commercially available reagents (Easy MoAb CD4;Bio-D, Valenzano, Italy) and analyzed on the Auto40. The results were compared with those from the FACSCount system (Becton Dickinson, San Jose, USA). Repeatability analysis was performed on duplicate testing of 49 samples on both FACSCount and Auto40. The intra-run precision was measured by 10 replicates using 3 clinical blood samples with low, intermediate and high CD4 concentrations. The results from the two instruments were in good agreement. The percent similarity between the results of both instruments was 99%+/-relative standard deviation of 12.7%. The concordance correlation coefficient was 0.99. The absolute bias and limits of agreement (LOA) between the two instruments, calculated by Bland-Altman analysis, were clinically acceptable (bias: +4 cells/mul; LOA: -111 to +120 cells/mul). The clinical agreement between the two instruments at a cutoff of 200 CD4 cells/mul was 94%. The repeatability of measurements on the Auto40 was also similar to that observed with FACSCount system (bias +0.1 cells/mul, coefficient of variation 2.5% vs bias -1.1cells/mul, coefficient of variation 2.9% respectively). In conclusion, our results indicate that the Auto 40 system, using thermoresistant reagents, is suitable for CD4 T cell enumeration and will be a helpful tool to improve HIV laboratory monitoring in resource-limited settings
Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines
No full textSUMMARY: Mathematical models predict that the future of epidemics of drug-resistant pathogens depends in part on the competitive fitness of drug-resistant strains. Considering metacyclogenesis (differentiation process essential for infectivity) as a major contributor to the fitness of Leishmania donovani, we tested its relationship with pentavalent antimony (SbV) resistance in clinical lines. Different methods for the assessment of metacyclogenesis were cross-validated: gene expression profiling (META1 and SHERP), morphometry (microscopy and FACS), in vitro infectivity to macrophages and resistance to complement lysis. This was done on a model constituted by 2 pairs of reference strains cloned from a SbV-resistant and -sensitive isolate. We selected the most adequate parameter and extended the analysis of metacyclogenesis diversity to a sample of 20 clinical lines with different in vitro susceptibility to the drug. The capacity of metacyclogenesis, as measured by the complement lysis test, was shown to be significantly higher in SbV-resistant clinical lines of L. donovani than in SbV-sensitive lines. Together with other lines of evidence, it is concluded that L. donovani constitutes a unique example and model of drug-resistant pathogens with traits of increased fitness. These findings raise a fundamental question about the potential risks of selecting more virulent pathogens through massive chemotherapeutic interventions
Economic implications of three strategies for the control of taeniasis
No full textObjective To evaluate the cost-effectiveness of three strategies for the control of taeniasis in a community, in terms of cost per case treated. Methods A study was conducted in South India to determine the prevalence of taeniasis by screening stool samples from 653 randomly chosen subjects, for coproantigens. The costs incurred in the project were used to estimate the cost per case screened and treated. A one-way sensitivity analysis was carried out for varying rates of taeniasis, different screening strategies and mass therapy. Further sensitivity analysis was carried out with different manpower and test costs. Results The rate of taeniasis as detected by ELISA for coproantigen was 3 per 1000 (2 of 653 samples). Our study showed that mass therapy without screening for taeniasis would be the most economical strategy in terms of cost per case treated if field workers are employed exclusively for either mass therapy or screening. For each strategy, costs per case treated are higher at low prevalence of taeniasis, with a sharp rise below 15%. Conclusions In places that are endemic for taeniasis and neurocysticercosis, mass therapy or screening for taeniasis should be considered. Screening by stool microscopy is not cost-effective in terms of cost per case of taeniasis treated owing to its low sensitivity. Although the cost per case of taeniasis treated is high at low prevalence of taeniasis for all options, incorporating mass therapy into existing mass drug distribution programmes might prove to be the most cost-effective control strategy
Analysis of the editorial process of the multidisciplinary rural development journal Tropicultura
No full textPredictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia
No full textThe objectives of this study were to examine the association of the on-treatment CD4 cell count with late mortality (after >6 months of antiretroviral treatment [ART]) and to identify the determinants of the long-term CD4 cell count evolution after treatment initiation. We conducted a retrospective analysis including all antiretroviral (ARV)-naive adults initiating ART in a tertiary hospital in Phnom Penh, Cambodia from 2003-2010. We used Cox proportional hazards modelling (mortality analysis), including time-updated CD4 counts, and mixed-effects modelling (CD4 response over time). Overall, 2840 patients were included (47% male, median age: 34 years, median baseline CD4 count: 78 cells/muL). The median time on ART was 2.5 years (IQR 1.1-4.3); 71 patients died after >6 months of ART. The baseline CD4 count was the main determinant of the on-treatment CD4 cell count. Time-updated CD4 cell counts was the strongest determinant of late mortality with a HR of 0.32 (95% CI 0.16-0.63) and 0.29 (95% CI 0.11-0.71) for CD4 values of 200-350 cells/muL and 350-500 cells/muL respectively. We conclude that baseline CD4 counts strongly determine the long-term immune recovery, which critically affects late mortality. This calls for increased efforts for early ART initiation and availability of CD4 count testing in low-income countries
Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India
No full textBACKGROUND: Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India. METHODS: The study included all patients with newly diagnosed VL-HIV coinfection and initiating treatment with liposomal amphotericin B (20-25 mg/kg in 4-15 days) between July 2007 and September 2010. Kaplan-Meier estimates of the cumulative incidence of death/treatment failure were calculated. RESULTS: Fifty-five patients were included (83.6% male; median age, 35 years; 62% migrant laborers; median follow-up, 1 year). The median CD4 cell count at VL diagnosis was 66 cells/muL (interquartile range, 38-112). Twenty-seven patients (49.1%) presented with VL relapse of VL. The overall tolerance of liposomal amphotericin B was excellent, with no interrupted treatment. Survival by 1 and 2 years after VL treatment was estimated at 85.5%. No patients had initial treatment failure. The probabilities of VL relapse were 0%, 8.1%, and 26.5% at 0.5, 1, and 2 years after VL treatment, respectively; relapse rates were similar for primary VL and VL relapse. CD4 counts <200 cells/muL at 6 months after cART initiation were predictive of subsequent relapse. The mean CD4 cell counts at 6 and 24 months after cART initiation were 187 and 261 cells/muL, respectively. The rate for retention in HIV care was 83.6%. CONCLUSIONS: Good long-term survival and retention rates were obtained for VL-HIV-coinfected patients treated with liposomal amphotericin B and cART. Although the initial VL treatment response was excellent, VL relapse within 2 years remained frequent
