Differentiating central nervous system infection from disease infiltration in hematological malignancy.

Hematological malignancies place individuals at risk of CNS involvement from their hematological disease and opportunistic intracranial infection secondary to disease-/treatment-associated immunosuppression. Differentiating CNS infection from hematological disease infiltration in these patients is valuable but often challenging. We sought to determine if statistical models might aid discrimination between these processes. Neuroradiology, clinical and laboratory data for patients with hematological malignancy at our institution between 2007 and 2017 were retrieved. MRI were deep-phenotyped across anatomical distribution, presence of pathological enhancement, diffusion restriction and hemorrhage and statistically modelled with Bayesian-directed probability networks and multivariate logistic regression. 109 patients were studied. Irrespective of a diagnosis of CNS infection or hematological disease, the commonest anatomical distributions of abnormality were multifocal-parenchymal (34.9%), focal-parenchymal (29.4%) and leptomeningeal (11.9%). Pathological enhancement was the most frequently observed abnormality (46.8%), followed by hemorrhage (22.9%) and restricted diffusion (19.3%). Logistic regression could differentiate CNS infection from hematological disease infiltration with an AUC of 0.85 where, with OR > 1 favoring CNS infection and < 1 favoring CNS hematological disease, significantly predictive imaging features were hemorrhage (OR 24.61, p = 0.02), pathological enhancement (OR 0.17, p = 0.04) and an extra-axial location (OR 0.06, p = 0.05). In conclusion, CNS infection and hematological disease are heterogeneous entities with overlapping radiological appearances but a multivariate interaction of MR imaging features may assist in distinguishing them.

National review of reported Yellow fever vaccine incidents in the UK.

BACKGROUND: Yellow fever (YF) vaccination is the single most important preventative measure against YF infection, however the live attenuated vaccine has associated serious adverse events. All YF vaccinations in England, Wales and Northern Ireland (EWNI) are administered in YF Vaccination Centres and comply with National Travel Health Network and Centre (NaTHNaC) Conditions of Designation and Code of Practice, including reporting of vaccine incidents to NaTHNaC. In this study we evaluated the number and type of YF vaccine incidents in EWNI to identify areas for improvement. METHODS: NaTHNaC's telephone advice line database was retrospectively searched from 1st January 2016 to 31st December 2018 for YF vaccine incidents. Calls were categorised and analysed according to incident type. RESULTS: Seventy-eight YF vaccine incidents were reported from a total of 17250 calls. The commonest incident was incorrect timing of measles, mumps and rubella vaccine in relation to YF vaccine, where the recommended 28-day interval was not observed (n = 21). Other incidents included accidental partial vaccination (n = 11), inappropriate vaccination (n = 5) and invalid vaccination due to expiry or cold chain breach (n = 4). Inadvertent vaccination in contraindicated individuals occurred in two travellers with thymectomies (resulting in one death), and five immunocompromised travellers. CONCLUSIONS: YF vaccine incidents represent a small proportion of total calls. Similar incidents likely occur with other vaccines, but YF vaccine incidents are of particular concern; whilst most incidents were not harmful, vaccination in contraindicated individuals resulted in one death. These findings helped to inform new guidance and update training for staff in YF vaccination centres.

Challenges in the management of slowly growing non-tuberculous mycobacteria causing pulmonary disease: Perspectives from a high burden country.

PURPOSE: There is a dearth of data on epidemiology, diagnosis and management of slow growing non tuberculous mycobacteria(NTM) in India, despite being a TB endemic country. This study aims to describe the geographic distribution, risk factors, and the challenges in management of slow growing NTM causing pulmonary infections. METHODS: Over a period of 3 years, all slow growing NTM received from pulmonary specimens at a tertiary care centre were further studied from electronic hospital records to correlate non tuberculous mycobacteria species with demographics, geographic location, describe comorbidities including immunosuppression, radiologic findings and treatment regimes. RESULTS: M.intracellullare was found in the majority of isolates with significant geographic variation and M.simiae the second commonest found exclusively in southern states. Common comorbidities included a previous history of treatment for tuberculosis, structural lung disease as well as systemic risk factors. Disseminated disease only occurred in immunocompromised hosts as was expected, but at a high rate of 44%. Treatment completion and outcomes were difficult to attain in our population. CONCLUSION: The burden of NTM infection and its management in India remain a challenge. Ensuring it is made a notifiable disease may improve the current situation.

Mycoplasma genitalium: A Review.

Mycoplasma genitalium is a fastidious organism of the class Mollicutes, the smallest prokaryote capable of independent replication. First isolated in 1981, much is still unknown regarding its natural history in untreated infection. It is recognized as a sexually transmitted pathogen causing acute and chronic non-gonococcal urethritis (NGU) in men, with a growing body of evidence to suggest it also causes cervicitis and pelvic inflammatory disease in women. Its role in several other clinical syndromes is uncertain. The majority of people infected remain asymptomatic and clear infection without developing disease; asymptomatic screening is therefore not recommended. Prevalence rates are higher in patients attending sexual health clinics and in men with NGU. Limited availability of diagnostics has encouraged syndromic management, resulting in widespread antimicrobial resistance and given that few antimicrobial classes have activity against M. genitalium, there is significant concern regarding the emergence of untreatable strains. There is a need for wider availability of testing, which should include detection of macrolide resistance mediating mutations. Expertise in interpretation of microbiological results with clinical correlation ensures targeted treatment avoiding unnecessary antibiotic exposure. Public health surveillance nationally and internationally is vital in monitoring and responding to changing epidemiology trends. In this review, we summarize current knowledge of M. genitalium, including epidemiology, clinical and microbiological data, and discuss treatment challenges in the era of rising multidrug resistance.

A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.