Species status of Neisseria gonorrhoeae: Evolutionary and epidemiological inferences from multilocus sequence typing

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2007 Bennett et al; licensee BioMed Central Ltd.Background: Various typing methods have been developed for Neisseria gonorrhoeae, but none provide the combination of discrimination, reproducibility, portability, and genetic inference that allows the analysis of all aspects of the epidemiology of this pathogen from a single data set. Multilocus sequence typing (MLST) has been used successfully to characterize the related organisms Neisseria meningitidis and Neisseria lactamica. Here, the same seven locus Neisseria scheme was used to characterize a diverse collection of N. gonorrhoeae isolates to investigate whether this method would allow differentiation among isolates, and to distinguish these three species. Results: A total of 149 gonococcal isolates were typed and submitted to the Neisseria MLST database. Although relatively few (27) polymorphisms were detected among the seven MLST loci, a total of 66 unique allele combinations (sequence types, STs), were observed, a number comparable to that seen among isolate collections of the more diverse meningococcus. Patterns of genetic variation were consistent with high levels of recombination generating this diversity. There was no evidence for geographical structuring among the isolates examined, with isolates collected in Liverpool, UK, showing levels of diversity similar to a global collection of isolates. There was, however, evidence that populations of N. meningitidis, N. gonorrhoeae and N. lactamica were distinct, with little support for frequent genetic recombination among these species, with the sequences from the gdh locus alone grouping the species into distinct clusters. Conclusion: The seven loci Neisseria MLST scheme was readily adapted to N. gonorrhoeae isolates, providing a highly discriminatory typing method. In addition, these data permitted phylogenetic and population genetic inferences to be made, including direct comparisons with N. meningitidis and N. lactamica. Examination of these data demonstrated that alleles were rarely shared among the three species. Analysis of variation at a single locus, gdh, provided a rapid means of identifying misclassified isolates and determining whether mixed cultures were present.This study is funded by the Wellcome Trust and European Unio

Improving tuberculosis diagnosis: Better tests or better healthcare?

In a Perspective accompanying Sylvia and colleagues, Carlton Evans and colleagues discuss the challenge of squaring policies around tuberculosis diagnosis with the realities of clinical practice in small villages and low-resource settings

COVID-19, tuberculosis and poverty: preventing a perfect storm

The global health community must learn from COVID-19 and take action now on tuberculosis and its social determinants, potentially saving millions from a preventable and curable disease https://bit.ly/2LLgLg

Why do patients with multimorbidity in England report worse experiences in primary care? Evidence from the General Practice Patient Survey.

OBJECTIVES: To describe and explain the primary care experiences of people with multiple long-term conditions in England. DESIGN AND METHODS: Using questionnaire data from 906,578 responders to the English 2012 General Practice Patient Survey, we describe the primary care experiences of patients with long-term conditions, including 583,143 patients who reported one or more long-term conditions. We employed mixed effect logistic regressions to analyse data on six items covering three care domains (access, continuity and communication) and a single item on overall primary care experience. We controlled for sociodemographic characteristics, and for general practice using a random effect, and further, controlled for, and explored the importance of, health-related quality of life measured using the EuroQoL (EQ-5D) scale. RESULTS: Most patients with long-term conditions report a positive experience of care at their general practice (after adjusting for sociodemographic characteristics and general practice, range 74.0-93.1% reporting positive experience of care across seven questions) with only modest variation by type of condition. For all three domains of patient experience, an increasing number of comorbid conditions is associated with a reducing percentage of patients reporting a positive experience of care. For example, compared with respondents with no long-term condition, the OR for reporting a positive experience is 0.83 (95% CI 0.80 to 0.87) for respondents with four or more long-term conditions. However, this relationship is no longer observed after adjusting for health-related quality of life (OR (95% CI) single condition=1.23 (1.21 to 1.26); four or more conditions=1.31 (1.25 to 1.37)), with pain making the greatest difference among five quality of life variables included in the analysis. CONCLUSIONS: Patients with multiple long-term conditions more frequently report worse experiences in primary care. However, patient-centred measures of health-related quality of life, especially pain, are more important than the number of conditions in explaining why patients with multiple long-term conditions report worse experiences of care

Quality of life, tuberculosis and treatment outcome; a case-control and nested cohort study

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities 13/7/2016-24/2/2018 and followed-up until 8/11/2019. Inclusion criteria were: age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly-selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with: QOL; health; energy; activities of daily living (ADL); self; relationships; money; and living place. FINDINGS: Newly-diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13-points had 4.2-times (95%CI=2.3,7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later and for patients with successful treatment, QOL became similar to participants who never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psycho-socio-economic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL 8-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care

Evaluation of magnetic resonance imaging abnormalities in juvenile onset neuropsychiatric systemic lupus erythematosus.

The aim of this study was to describe the abnormalities identified with conventional MRI in children with neuropsychiatric systemic lupus erythematosus (NPSLE). This was single-centre (Great Ormond Street Hospital, London) retrospective case series of patients with juvenile NPSLE seen in 2003-2013. Brain MR images of the first episode of active NPSLE were reviewed. All patients fulfilled the 1999 ACR case definitions for NPSLE syndromes. Presenting neuropsychiatric manifestations, immunological findings and treatment are reported. Results are expressed as median and ranges or percentages. Fisher's exact test was used to identify clinical predictors of abnormal MRI. A total of 27 patients (22 females), median age 11 years (4-15), were identified. Presenting clinical symptoms included the following: headaches (85.1 %), mood disorder/depression (62.9 %), seizures (22.2 %), acute psychosis (18.5 %), cognitive dysfunction (14.8 %), movement disorder (14.8 %), acute confusional state (14.8 %), aseptic meningitis (7.4 %), demyelinating syndrome (3.7 %), myelopathy (3.7 %), dysautonomia (3.7 %) and cranial neuropathy (3.7 %). The principal MR findings were as follows: (1) absence of MRI abnormalities despite signs and symptoms of active NPSLE (59 %); (2) basilar artery territory infarction (3 %); (3) focal white matter hyperintensities on T2-weighted imaging (33 %); (4) cortical grey matter lesions (3 %); and (5) brain atrophy (18.5 %). The presence of an anxiety disorder strongly associated with abnormal MRI findings (p = 0.008). In over half the children with NPSLE, no conventional MRI abnormalities were observed; white matter hyperintensities were the most commonly described abnormalities. Improved MR techniques coupled with other alternative diagnostic imaging modalities may improve the detection rate of brain involvement in juvenile NPSLE

Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA) was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies