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Antiretroviral treatment in low-resource settings: what has changed in the last 10 years and what needs to change in the coming years?
No full textDengue and health care access: the role of social determinants of health in dengue surveillance in Colombia
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Should I get screened for sleeping sickness? A qualitative study in Kasai Province, Democratic Republic of Congo
No full textAnalysis of blood-brain barrier permeability of monovalent nanobodies using microdialysis
No full textBACKGROUND AND PURPOSE: Nanobodies are promising antigen-binding moieties for molecular imaging and therapeutic purposes due to their favorable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the central nervous system (CNS) remains to be demonstrated. EXPERIMENTAL APROACH: We have assessed the blood-brain barrier permeability of Nb_An33, a nanobody against the Trypanosoma brucei brucei Variant-specific Surface Glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, Single Photon Emission Computed Tomography (SPECT), or a combination of both methodologies. This enabled the quantification of unlabeled and (99m) Tc-labeled nanobodies using respectively a sensitive VSG-based nanobody-detection ELISA, radioactivity measurement in collected microdialysates, and SPECT image analysis. KEY RESULTS: The combined read-out methodologies demonstrate that disposition of Nb_An33 can be detected in the brain of healthy rats following intravenous injection and that inflammation-induced damage to the blood-brain barrier significantly increases the nanobody perfusion efficiency. We also illustrate the advantage of complementing SPECT analyses with intracerebral microdialysis in brain disposition studies and suggest that it is of interest to evaluate the blood-brain barrier penetrating potential of monovalent nanobodies in models of CNS-inflammation. The presented data also suggest that fast blood clearance might hamper efficient targeting of specific nanobodies to the CNS. CONCLUSIONS AND IMPLICATIONS: Nanobodies can perfuse into the brain parenchyma, especially in pathological conditions where the blood-brain barrier integrity is compromised
Effects of decontamination, DNA extraction and amplification procedures on the molecular diagnosis of Mycobacterium ulcerans disease (Buruli ulcer)
No full textWe compared two DNA extraction methods (a semi-automated method using Maxwell(R) kit and a modified Boom method) and three amplification procedures (a single-step PCR, a nested PCR and a real-time quantitative PCR) on 74 surgical tissue specimens from clinically suspected Buruli ulcer patients. All these procedures were compared before and after decontamination.We observed that, among the procedures tested, real-time PCR after the modified Boom extraction method or a single-run PCR assay after the Maxwell(R) 16 extraction method, performed on non-decontaminated suspensions are the best for the molecular diagnosis of Mycobacterium ulcerans disease
Sulfadoxine-pyrimethamine resistance and intermittent preventive treatment during pregnancy: a retrospective analysis of birth weight data in the Democratic Republic of Congo (DRC)
No full textObjective: To assess the effect of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) on birth weight in sites with varying degrees of drug resistance. Methods Birth weight data from three regions in Democratic Republic of Congo with varying degrees of sulfadoxine-pyrimethamine (SP) resistance (1.6% in Mikalayi, 21.7% in Kisangani and 60.6% in Rutshuru) were analysed retrospectively by means of a logistic model that included the number of SP doses taken by the mother and other potentials confounding factors. Results The IPTp-SP reduced the risk of low birth weight (LBW) in Kisangani (adjusted OR, 0.15; IC95%, 0.05-0.46) and in Mikalayi (adjusted OR, 0.12; IC95%, 0.01-0.89). In both sites, the average birth weight was higher for mothers having received two rather than one or no SP doses (P < 0.001). In Rutshuru, IPTp-SP had an effect in primigravidae but not in multigravidae. However, after adjustment for other LBW risk factors, there was no difference in the proportion of LBW (adjusted OR 0.92; IC95%, 0.37-2.25) between women having taken at least 2 SP doses and those with only one dose or none. Conclusion IPT-SP remains an effective strategy in Kisangani and Mikalayi where the therapeutic failure to SP in children with clinical malaria was 21.7% and 1.6%, respectively, while IPTp-SP effect seems lower in Rutshuru where the therapeutic failure to SP was 60.6%. The threshold value of SP resistance at which IPTp-SP fails to have a significant impact on birth weight and LBW is unknown. Considering that no alternative is currently available, additional studies on the efficacy of IPTp-SP in the areas of high SP resistance such as Rutshuru are needed so that the threshold at which this intervention fails to provide any benefit is determined with some precision
The immune reconstitution inflammatory syndrome related to HIV co-infections: a review
No full textThe immune reconstitution inflammatory syndrome (IRIS) is a consequence of an excessive pathogen-specific immune recovery reaction and occurs in a subset of patients on antiretroviral therapy (ART). Infective forms of IRIS may present either as an 'unmasking' of a previously subclinical infection or the paradoxical clinical deterioration of an infection for which the patient received appropriate antimicrobial therapy. The most important risk factors for IRIS are a low CD4+ T-cell count and a short time between treatment of the infection and the commencement of ART. The general approach to the treatment of IRIS is to continue ART and provide antimicrobial therapy for the provoking infection. The majority of cases are self-limiting; however, mortality and hospitalisation rates are particularly high when tuberculosis- or cryptococcal-IRIS affects the central nervous system (CNS). Corticosteroid therapy should be considered in certain forms of IRIS after the exclusion of other conditions that could explain the inflammatory manifestations in the patients. Given that a low CD4+ T-cell count is a major risk factor for the development of IRIS, commencing ART at a CD4+ T-cell count of >350/muL will prevent most cases
