Whole-Genome Sequencing as Tool for Investigating International Tuberculosis Outbreaks: A Systematic Review

Background: Whole-genome sequencing (WGS) can support the investigation of tuberculosis (TB) outbreaks. The technique has been applied to estimate the timing and directionality of transmission and to exclude cases from an investigation. This review assesses how WGS was applied in international outbreak investigations and discusses the advantages and challenges of the application of WGS.Methods: Databases were searched for reports on international TB outbreak investigations. Information was extracted on: Why was WGS applied?; How was WGS applied?; Organizational issues; WGS methodology; What was learned/what were the implications of the WGS investigation?; and challenges and lessons learned.Results: Three studies reporting on international outbreak investigations were identified. Retrospective WGS sequencing was performed in all studies and prospective typing in two to study TB transmission. In one study, WGS data were produced centrally (i.e., in one laboratory) and analysis was done centrally. In two studies, WGS data production was done in a decentralized manner, and analysis was centralized in one laboratory. Three groups of professionals were involved in the international outbreak investigation: public health authorities, laboratory experts, and clinicians. The reported WGS methodology applied differed between the studies in some aspects, e.g., sequencing platform; quality measures, percentage of the reference genome covered, and the mean genomic coverage; analysis, use of a reference genome or de novo assembly; and software used for alignment and analysis. In all three studies, in-house scripts were used for variance calling, and the single nucleotide polymorphism (SNP) approach was used for analysis. All outbreak investigation reports stated that WGS refuted suspected transmission events and provided supporting evidence for epidemiological data. Several challenges were reported of which most were not related to WGS. The only challenge related to WGS was the timeframe of getting WGS data if WGS is not routinely performed.Conclusions: WGS was considered a useful addition in international TB outbreak investigations. Further standardization of the WGS methodology and good structures for international collaboration and coordination are needed to take full advantage of this new technology. Whether the use of WGS results in earlier detection of cases and thus limits transmission still needs to be determined

Knowledge of tuberculosis-treatment prescription of health workers: a systematic review

Treating tuberculosis (TB) patients with inappropriate treatment regimens can lead to treatment failure and, thus, patients who have not been cured and/or to the development of (multi)-drug resistance. A systematic review was performed to assess the knowledge of appropriate TB drug regimens among all categories of healthcare workers (HCWs)

European Union standard for tuberculosis care on treatment of multidrug-resistant tuberculosis following new World Health Organization recommendations

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Extrapulmonary Tuberculosis by Nationality, the Netherlands, 1993–2001

The growth of the number of inhabitants with a non-Western ethnic background most likely explains the growth of extrapulmonary TB in the Netherlands

Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Methodology/Principal Findings: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. Conclusions/Significance: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship

Tuberculosis-HIV Co-infection in Kiev City, Ukraine

In 2004, we tested all patients with newly diagnosed tuberculosis (TB) for HIV in Kiev City. The results were compared to information from medical records of 2002, when co-infection prevalence was 6.3%. Of 968 TB patients, 98 (10.1%) were HIV infected. TB-HIV co-infection is increasing, especially in injecting drug users

Cognitive Functioning in Patients with Bipolar Disorder: Association with Depressive Symptoms and Alcohol Use

BACKGROUND: Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored. METHODOLOGY/PRINCIPAL FINDINGS: The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R(2) 7%), speed of information processing (adjusted beta 0.36; R(2) 20%), attentional switching (adjusted beta 0.24; R(2) 16%) and the mean score (adjusted beta 0.23; R(2) 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction. CONCLUSIONS/SIGNIFICANCE: Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder

Obstacles for optimal tuberculosis case detection in primary health centers (PHC) in Sidoarjo district, East Java, Indonesia

Pulmonary tuberculosis (TB) is a major health problem worldwide. Detection of the most infectious cases of tuberculosis - sputum smear-positive pulmonary cases - by passive case finding is an essential component of TB control. The district of Sidoarjo in East Java reported a low case detection rate (CDR) of 14% in 2003. We evaluated the diagnostic process for TB in primary health care centers (PHC) in Sidoarjo district to assess whether problems in identification of TB suspects or in diagnosing TB patients can explain the low CDR. We performed interviews with the staff (general nurse, TB worker, laboratory technician, and head of health center) of the 25 PHCs of Sidoarjo district to obtain information about the knowledge of TB, health education practices, and availability of support services for TB diagnosis. The quality of the laboratory diagnosis was examined by providing 10 slides with a known result to the laboratory technicians for re-examination. Eighty percent of the nurses and 84% of the TB workers knew that cough >3 weeks can be a symptom of TB. Only 40% of the nurses knew the cause of TB, few could mention complications of TB and none could mention the duration of infectiousness after start of treatment. Knowledge of TB workers was much better. Information about how to produce a good sputum sample was provided to TB suspects by 76% of the nurses and 84% of the TB workers. Only few provided all information. Fifty-five percent of the 11 laboratory technicians correctly identified all positive slides as positive and 45% correctly identified 100% of the negative slides as negative. All TB workers, one general nurses and 32% of the laboratory technicians had received specific training in TB control. There has been no shortage of TB forms and laboratory materials in 96% of the PHCs. The quality of the diagnostic process for TB at PHC in Sidoarjo district should be improved on all levels. Training in TB control of all general nurses and the laboratory technicians that have not received training would be a good first step to enhance diagnosis of TB and to improve the case detection rat