The HIV care cascade: models,measures and moving forward

Introduction

This article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.

Discussion

Questions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm³; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.

Conclusions

There is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.     

Dorsal costo-vertebral joint as a rare localization of Staphylococcus aureus sepsis

Background

Septic arthritis of the costovertebral thoracic joint is a rare site infection. We report an isolated case of septic arthritis of the 10th costo-vertebral right joint with osteitis due to Staphylococcus aureus.

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a life-threatening encephalitis. In order to treat those infections properly, it is necessary to target the treatment not only to the trophozoite but also to the cyst. Furthermore, it may be advantageous to avoid parasite killing by necrosis, which may induce local inflammation. We must also avoid toxicity of host tissue. Many drugs which target eukaryotes are known to induce programmed cell death (PCD), but this process is poorly characterized in Acanthamoeba. Here, we study the processes of programmed cell death in Acanthamoeba, induced by several drugs, such as statins and voriconazole. We tested atorvastatin, fluvastatin, simvastatin, and voriconazole at the 50% inhibitory concentrations (IC₅₀s) and IC₉₀s that we have previously established. In order to evaluate this phenomenon, we investigated the DNA fragmentation, one of the main characteristics of PCD, with quantitative and qualitative techniques. Also, the changes related to phosphatidylserine exposure on the external cell membrane and cell permeability were studied. Finally, because caspases are key to PCD pathways, caspase activity was evaluated in Acanthamoeba. All the drugs assayed in this study induced PCD in Acanthamoeba. To the best of our knowledge, this is the first study where PCD induced by drugs is described quantitatively and qualitatively in Acanthamoeba.     

A 6q14.1‐q15 microdeletion in a male patient with severe autistic disorder,lack of oral language,and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1‐q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate.     

Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru

Pathogenic strains of Acanthamoeba genus are the causative agents of fatal granulomatous amoebic encephalitis and a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. In a previous study, Acanthamoeba strains were isolated from nasal swabs collected from healthy individuals in Peru. In the present study, the pathogenic potential of the isolated strains was established based on temperature and osmotolerance assays as well as the secretion rate of extracellular proteases. Based on these experiments, four strains that showed the highest pathogenic potential were selected for sensitivity assays against two molecules (voriconazole and chlorhexidine) which are currently used for the treatment of Acanthamoeba infections. After performing sensitivity and activity assays, it was found that both drugs were active against the tested strains. However, voriconazole showed higher activity against the studied strains compared to chlorhexidine. Therefore, voriconazole should be established as a first-line treatment against Acanthamoeba infections at least in the studied region of Peru.     

Frequency and clinicopathological features of fibroelastotic changes in the gastrointestinal tract

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention.