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Syphilis is an ancient condition which still is of global concern today. Despite better awareness amongst clinicians and improving diagnostics, it remains likely underdiagnosed in part because of its namesake the 'great imitator.' While many patients suffer primary or secondary disease, tertiary syphilis characterised by gumma is rare, especially in the context of neurosyphilis. Here, we report a rare case of a well-controlled human immunodeficiency virus- (HIV-) positive gentleman with a history of previous syphilis and epilepsy who presented with progressive left leg weakness leading to immobility and altered bowels and, on neurological examination, Brown-Sequard syndrome. Magnetic resonance imaging (MRI) of the spine revealed two peripherally enhancing cavitating lesions at T4-T5 with associated meningeal thickening and cord oedema. Cerebrospinal fluid (CSF) analysis revealed high protein (3.07 g/dL) and white cell count (7 × 109/L) with negative cryptococcal antigen, tuberculosis molecular testing (GeneXpert), microscopy and culture, and viral polymerase chain reaction (PCR). CSF serology was positive for Treponema pallidum particle agglutination (TPPA) 10240 and RPR 1 in 2 suggesting active disease. While TB treatment had been started prior to these investigations on day 11, 14-day high-dose benzylpenicillin therapy commenced. Repeat MRI of the spine at days 12 and 22 showed incremental improvements in all parameters which correlated with improving functionality and neurology. According to our literature search, this represents the 13th case recorded for spinal syphilitic gumma and the only case recorded in a HIV-positive individual and adds to the evidence that, in the absence of rapidly changing neurology, medical management can lead to good clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Blood-stream infection (BSI) is one of the principle determinants of the morbidity and mortality associated with advanced HIV infection, especially in sub-Saharan Africa. Over the last 10 years, there has been rapid roll-out of anti-retroviral therapy (ART) and cotrimoxazole prophylactic therapy (CPT) in many high HIV prevalence African countries. Methods: A prospective cohort of adults with suspected BSI presenting to Queen's Hospital, Malawi was recruited between 2009 and 2010 to describe causes of and outcomes from BSI. Comparison was made with a cohort pre-dating ART roll-out to investigate whether and how ART and CPT have affected BSI. Malawian census and Ministry of Health ART data were used to estimate minimum incidence of BSI in Blantyre district. Results: 2,007 patients were recruited, 90% were HIV infected. Since 1997/8, culture-confirmed BSI has fallen from 16% of suspected cases to 10% (p<0.001) and case fatality rate from confirmed BSI has fallen from 40% to 14% (p<0.001). Minimum incidence of BSI was estimated at 0.03/1000 years in HIV uninfected vs. 2.16/1000 years in HIV infected adults. Compared to HIV seronegative patients, the estimated incidence rate-ratio for BSI was 80 (95% CI:46–139) in HIV-infected/untreated adults, 568 (95% CI:302–1069) during the first 3 months of ART and 30 (95% CI:16–59) after 3 months of ART. Conclusions: Following ART roll-out, the incidence of BSI has fallen and clinical outcomes have improved markedly. Nonetheless, BSI incidence remains high in the first 3 months of ART despite CPT. Further interventions to reduce BSI-associated mortality in the first 3 months of ART require urgent evaluation. [ABSTRACT FROM AUTHOR]

A 45-year-old man from Pakistan presented with two raised and nodular plaques on his left arm that had been present since birth. He habitually scratched the lesions. The patient had no relevant medical history and denied contact with animals or recent travel. Biopsies revealed granulomatous inflammation, and further testing confirmed the presence of Mycobacterium tuberculosis (Mtb). The patient received antituberculosis therapy, leading to significant improvement in the skin lesions. This case highlights the importance of considering cutaneous Mtb in cases of chronic lesions with non-necrotizing granulomas and emphasizes the need for tissue culture to confirm the diagnosis and initiate prompt treatment. [Extracted from the article]

Background. Invasive nontyphoid Salmonella (iNTS) disease is common and severe in adults with human immunodeficiency virus (HIV) infection in Africa. We previously observed that ex vivo macrophages from HIV-infected subjects challenged with Salmonella Typhimurium exhibit dysregulated proinflammatory cytokine responses. Methods. We studied the transcriptional response in whole blood from HIV-positive patients during acute and convalescent iNTS disease compared to other invasive bacterial diseases, and to HIV-positive and -negative controls Results. During iNTS disease, there was a remarkable lack of a coordinated inflammatory or innate immune signaling response. Few interferon c (IFNc)-induced genes or Toll-like receptor/transcription factor nuclear factor jB (TLR/NFjB) gene pathways were upregulated in expression. Ex vivo lipopolysacharide (LPS) or flagellin stimulation of whole blood, however, showed that convalescent iNTS subjects and controls were competent to mount prominent TLR/NFjB-associated patterns of mRNA expression. In contrast, HIV-positive patients with other invasive bacterial infections (Escherichia coli and Streptococcus pneumoniae) displayed a pronounced proinflammatory innate immune transcriptional response. There was also upregulated mRNA expression in cell cycle, DNA replication, translation and repair, and viral replication pathways during iNTS. These patterns persisted for up to 2 months into convalescence Conclusions. Attenuation of NFjB-mediated inflammation and dysregulation of cell cycle and DNA-function gene pathway expression are key features of the interplay between iNTS and HIV. [ABSTRACT FROM AUTHOR]

Pregnant women undergoing long-term organ transplant treatment have an increased incidence of delivering infants with intrauterine growth restriction (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect evidence suggests that IUGR might result from an effect of cyclosporine A on amino acid transport by the placenta. In this study we tested the hypothesis that the transport of an essential amino acid, taurine, by fetal tissue other than the placenta is modulated by cyclosporine A.Cord blood cells (CBCs) were used to test this hypothesis as an easily obtainable fetal tissue. Transport of taurine into CBCs was measured using standard tracer flux assays.Uptake of [3H] taurine by CBCs was linear over 15 minutes (76.2 ± 16.6 fmol/106 cells/min, mean ± SEM, n = 6) and inhibitable by 10 mM β-alanine, a substrate of the system-β taurine transport protein (6.7 ± 1.0 fmol/106 cells/min, n = 6, P < .05, paired Student t test). Pre-incubation with cyclosporine A (5 μM) inhibited [3H] taurine uptake by 29.3%–5.3% (n = 8, P < .05, paired Student t test).These data show that amino acid transport via system-β can be measured in CBCs and may be a useful model for amino acid transport studies in fetal cells. We also show that system-β was inhibited by the immunosuppressant, cyclosporine A. This suggests that the increased incidence of IUGR reported in mothers treated with cyclosporine A may be due partially to effects on taurine uptake into fetal cells outside the placenta. [Copyright &y& Elsevier]

Background: The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes.Patients and methods: From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases.Results: A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention.Conclusions: Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure. [ABSTRACT FROM AUTHOR]

Background: Invasive nontyphoid Salmonella (iNTS) disease is common and severe in adults with human immunodeficiency virus (HIV) infection in Africa. We previously observed that ex vivo macrophages from HIV-infected subjects challenged with Salmonella Typhimurium exhibit dysregulated proinflammatory cytokine responses.Methods: We studied the transcriptional response in whole blood from HIV-positive patients during acute and convalescent iNTS disease compared to other invasive bacterial diseases, and to HIV-positive and -negative controls.Results: During iNTS disease, there was a remarkable lack of a coordinated inflammatory or innate immune signaling response. Few interferon γ (IFNγ)-induced genes or Toll-like receptor/transcription factor nuclear factor κB (TLR/NFκB) gene pathways were upregulated in expression. Ex vivo lipopolysacharide (LPS) or flagellin stimulation of whole blood, however, showed that convalescent iNTS subjects and controls were competent to mount prominent TLR/NFκB-associated patterns of mRNA expression. In contrast, HIV-positive patients with other invasive bacterial infections (Escherichia coli and Streptococcus pneumoniae) displayed a pronounced proinflammatory innate immune transcriptional response. There was also upregulated mRNA expression in cell cycle, DNA replication, translation and repair, and viral replication pathways during iNTS. These patterns persisted for up to 2 months into convalescence.Conclusions: Attenuation of NFκB-mediated inflammation and dysregulation of cell cycle and DNA-function gene pathway expression are key features of the interplay between iNTS and HIV. [ABSTRACT FROM AUTHOR]