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Severe strongyloidiasis: a systematic review of case reports
No full textBACKGROUND: Strongyloidiasis is commonly a clinically unapparent, chronic infection, but immuno suppressed subjects can develop fatal disease. We carried out a review of literature on hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), in order to describe the most challenging aspects of severe strongyloidiasis. METHODS: We conducted a structured search using PubMed to collect case reports and short case series on HS/DS published from 1991 to 2011. We restricted search to papers in English, Spanish, Italian and French. Case reports were classified as HS/DS according to given definitions. RESULTS: Records screened were 821, and 311 were excluded through titles and abstract evaluation. Of 510 full-text articles assessed for eligibility, 213 were included in qualitative analysis. As some of them were short case series, eventually the number of cases analyzed was 244.Steroids represented the main trigger predisposing to HS and DS (67% cases): they were mostly administered to treat underlying conditions (e.g. lymphomas, rheumatic diseases). However, sometimes steroids were empirically prescribed to treat signs and symptoms caused by unsuspected/unrecognized strongyloidiasis. Diagnosis was obtained by microscopy examination in 100% cases, while serology was done in a few cases (6.5%). Only in 3/29 cases of solid organ/bone marrow transplantation there is mention of pre-transplant serological screening. Therapeutic regimens were different in terms of drugs selection and combination, administration route and duration. Similar fatality rate was observed between patients with DS (68.5%) and HS (60%). CONCLUSIONS: Proper screening (which must include serology) is mandatory in high - risk patients, for instance candidates to immunosuppressive medications, currently or previously living in endemic countries. In some cases, presumptive treatment might be justified. Ivermectin is the gold standard for treatment, although the optimal dosage is not clearly defined in case of HS/DS
The health systems funding platform and World Bank legacy: the gap between rhetoric and reality
No full textNeopterin is a cerebrospinal fluid marker for treatment outcome evaluation in patients affected by Trypanosoma brucei gambiense sleeping sickness
No full textBACKGROUND: Post-therapeutic follow-up is essential to confirm cure and to detect early treatment failures in patients affected by sleeping sickness (HAT). Current methods, based on finding of parasites in blood and cerebrospinal fluid (CSF) and counting of white blood cells (WBC) in CSF, are imperfect. New markers for treatment outcome evaluation are needed. We hypothesized that alternative CSF markers, able to diagnose the meningo-encephalitic stage of the disease, could also be useful for the evaluation of treatment outcome. METHODOLOGYPRINCIPAL FINDINGS: Cerebrospinal fluid from patients affected by HAT and followed for two years after treatment was investigated. The population comprised stage 2 (S2) patients either cured or experiencing treatment failure during the follow-up. IgM, neopterin, B2MG, MMP-9, ICAM-1, VCAM-1, CXCL10 and CXCL13 were first screened on a small number of HAT patients (n = 97). Neopterin and CXCL13 showed the highest accuracy in discriminating between S2 cured and S2 relapsed patients (AUC 99% and 94%, respectively). When verified on a larger cohort (n = 242), neopterin resulted to be the most efficient predictor of outcome. High levels of this molecule before treatment were already associated with an increased risk of treatment failure. At six months after treatment, neopterin discriminated between cured and relapsed S2 patients with 87% specificity and 92% sensitivity, showing a higher accuracy than white blood cell numbers. CONCLUSIONSSIGNIFICANCE: In the present study, neopterin was highlighted as a useful marker for the evaluation of the post-therapeutic outcome in patients suffering from sleeping sickness. Detectable levels of this marker in the CSF have the potential to shorten the follow-up for HAT patients to six months after the end of the treatment
M48U1 CD4 mimetic has a sustained inhibitory effect on cell-associated HIV-1 by attenuating virion infectivity through gp120 shedding
No full textBACKGROUND: HIV-1 infected cells can establish new infections by crossing the vaginal epithelia and subsequently producing virus in a milieu that avoids the high microbicide concentrations of the vaginal lumen. FINDINGS: To address this problem, here, we report that pretreatment of HIV-infected peripheral blood mononuclear cells (PBMCs) with a 27 amino acid CD4-mimetic, M48U1, causes dramatic and prolonged reduction of infectious virus output, due to its induction of gp120 shedding. CONCLUSIONS: M48U1 may, therefore, be valuable for prophylaxis of mucosal HIV-1 transmission
Strategies for optimizing clinic efficiency in a community-based antiretroviral treatment programme in Uganda
No full textWe address a critical aspect of antiretroviral therapy (ART) scale-up: poor clinic organization leading to long waiting times and reduced patient retention. Using a before and after study design, time and motion studies and qualitative methods we evaluated the impact of triage and longer clinic appointment intervals (triage) on clinic efficiency in a community-based program in Uganda. We compared time waiting to see and time spent with providers for various patient categories and examined patient and provider satisfaction with the triage. Overall, median time spent at the clinic reduced from 206 to 83 min. Total median time waiting to see providers for stable-ART patients reduced from 102 to 20 min while that for patients undergoing ART preparation reduced 88-37 min. Improved patient flow, patient and provider satisfaction and reduced waiting times allowed for service delivery to more patients using the same staff following the implementation of triage
Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence?
No full textBACKGROUND: The active metabolites of tenofovir (TFV) and emtricitabine (FTC) in peripheral blood mononuclear cells (PBMCs) have been used as markers of long-term antiretroviral (ARV) adherence. However, the process of isolating PBMCs is expensive, complex, and not feasible in many settings. We compared concentrations of TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in the upper layer packed cells (ULPC) obtained after whole blood centrifugation to isolated PBMCs as a possible alternative marker of adherence. METHODS:: Ten HIV+ adults with HIV RNA <50 copies/mL on a TDF/FTC-containing regimen provided five paired PBMC and ULPC samples over 6h. TFV-DP and FTC-TP concentrations were analyzed by liquid chromatography/mass spectrometry (LC-MS/MS). Partial areas under the curve (AUC) were calculated using noncompartmental methods and Spearman Rank Correlations (rho) between PBMC and ULPC were determined. RESULTS:: The median (25-75 percentile) concentration of TFV-DP in PBMCs was 143 (103-248) fmol/10 cells and in ULPC was 227 (160-394) fmol/10 cells (rho=0.65;p <0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650-10000) fmol/10 cells and in ULPC was 19.0 (12.0-27.8) fmol/10 cells (rho 0.55;p<0.0001). Compared to PBMCs, ULPC TFV-DP was 64% higher and FTC-TP was 99.7% lower. ULPC concentrations of TFV-DP and FTC-TP in 1 additional subject receiving a single dose of TDF/FTC were only 0.05% and 25%, of the other 10 subjects, respectively. CONCLUSIONS:: ULPC concentrations significantly correlated with PBMC concentrations. Preliminary single-dose data suggest some discrimination between intermittent vs. consistent dosing. ULPC concentrations of TFV-DP and FTC-TP should be further investigated as a simply-collected, surrogate measure of ARV adherence
Traditional nets interfere with the uptake of long-lasting insecticidal nets in the peruvian Amazon: the relevance of net preference for achieving high coverage and use
No full textBACKGROUND: While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset(R) LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru. METHODS: The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses). RESULTS: A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset(R) LLINs ultimately did not. The LLINs' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001). CONCLUSION: Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent, appropriate quantitative and qualitative methods for collecting information on net preference should be developed before any LLIN procurement decision is made