Association between low 25(OH) vitamin D levels, antiretroviral therapy and metabolic profile in a cohort of treated ahd therapy naive HIV positive patients in Western Australia

See Attache

Failure of combined chloroquine and High-Dose primaquine therapy for plasmodium vivax malaria acquired in Guyana, South America

The presence of chloroquine-resistant Plasmodium vivax malaria in the New World has been suspected but not confirmed. We report the cases of three patients who acquired vivax malaria in Guyana, South America, and for whom standard chloroquine therapy (25 mg/kg) failed despite therapeutic blood levels. The optimal treatment of chloroquine-resistant P. vivax malaria is unknown, but recent studies suggest that a combination of chloroquine (25 mg/kg) and high-dose primaquine (2.5 mg/kg over 48 hours) is effective therapy. Two of our patients had recurrences of P. vivax malaria 6–8 weeks after receiving directly observed therapy with this combination. These cases confirm the presence of chloroquine-resistant P. vivax in Guyana and emphasize the need for better treatment regimens for chloroquine-resistant and primaquine-resistant P. vivax malaria

Antiviral Drug Allergy

Antiviral drugs used to treat HIV and hepatitis C are common causes of delayed drug hypersensitivities for which many of the more severe reactions have been recently shown to be immunogenetically mediated such as abacavir hypersensitivity where HLA-B*57:01 is now used routinely as a screening test to exclude patients carrying this allele from abacavir prescription. Most antiviral drug allergies consist of mild to moderate delayed rash without other serious features (e.g. fever, mucosal involvement, blistering rash, organ impairment. In these cases treatment can be continued with careful observation and symptomatic management and the discontinuation rate is low

Oral Challenge with Trimethoprim-Sulfamethoxazole in Patients with “Sulfa” Antibiotic Allergy

Letter to the Edito

HLAs: Key regulators of T-cell-mediated drug hypersensitivity

Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose-dependent. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast, off-target ADRs, including immune-mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response. IM-ADRs can be classified according to the primary immune cell involved and include B-cell-mediated (Gell-Coombs type I-III reactions) and T-cell-mediated (Gell-Coombs type IV or delayed hypersensitivity) reactions. IM-ADRs mediated by T cells are associated with phenotypically distinct clinical diagnoses and can vary from a mild delayed rash to a life-threatening cutaneous, systemic or organ disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and drug-induced liver disease. T-cell-mediated ADRs are strongly linked to the carriage of particular HLA risk alleles which are in the case of abacavir hypersensitivity and HLA-B*57:01 has led to translation into the clinic as a routine screening test. In this review, we will discuss the immunogenetics and pathogenesis of IM-ADRs and how HLA associations inform both pre-drug screening strategies and mechanistic understanding

Old dog begging for new tricks: current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity

Purpose of review: Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs. Recent findings: Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge. Although patch and intradermal testing are specific for the diagnosis of immune-mediated ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex-vivo diagnostics, especially enzyme-linked immunospot, has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous immune-mediated ADRs. Summary: In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct ‘allergy label’ is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction, is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T cell-mediated ADRs via personalized approaches, including human leukocyte antigen-typing, may pave future pathways to safer antimicrobial prescribing guidelines

Penicillin allergy labels drive perioperative prophylactic antibiotic selection in orthopedic procedures

'Clinical Communications' [No abstract

Readiness for PENicillin allergy testing: Perception of Allergy Label (PEN-PAL) Survey

Clinical Implications: Patients reporting penicillin allergy believe their allergy to be permanent, would take penicillins if tested negative, but are rarely referred for penicillin testing, leading to differential antibiotic utilization

Bounded and unitary elements in pro-C^*-algebras

A pro-C^*-algebra is a (projective) limit of C^*-algebras in the category of topological *-algebras. From the perspective of non-commutative geometry, pro-C^*-algebras can be seen as non-commutative k-spaces. An element of a pro-C^*-algebra is bounded if there is a uniform bound for the norm of its images under any continuous *-homomorphism into a C^*-algebra. The *-subalgebra consisting of the bounded elements turns out to be a C^*-algebra. In this paper, we investigate pro-C^*-algebras from a categorical point of view. We study the functor (-)_b that assigns to a pro-C^*-algebra the C^*-algebra of its bounded elements, which is the dual of the Stone-\v{C}ech-compactification. We show that (-)_b is a coreflector, and it preserves exact sequences. A generalization of the Gelfand-duality for commutative unital pro-C^*-algebras is also presented.Comment: v2 (accepted