Seasonality in pulmonary tuberculosis among migrant workers entering Kuwait

<p>Abstract</p> <p>Background</p> <p>There is paucity of data on seasonal variation in pulmonary tuberculosis (TB) in developing countries contrary to recognized seasonality in the TB notification in western societies. This study examined the seasonal pattern in TB diagnosis among migrant workers from developing countries entering Kuwait.</p> <p>Methods</p> <p>Monthly aggregates of TB diagnosis results for consecutive migrants tested between January I, 1997 and December 31, 2006 were analyzed. We assessed the amplitude (<it>α</it>) of the sinusoidal oscillation and the time at which maximum (<it>θ</it>°) TB cases were detected using Edwards' test. The adequacy of the hypothesized sinusoidal curve was assessed by <it>χ</it>²goodness-of-fit test.</p> <p>Results</p> <p>During the 10 year study period, the proportion (per 100,000) of pulmonary TB cases among the migrants was 198 (4608/2328582), (95% confidence interval: 192 – 204). The adjusted mean monthly number of pulmonary TB cases was 384. Based on the observed seasonal pattern in the data, the maximum number of TB cases was expected during the last week of April (<it>θ</it>° = 112°; <it>P </it>< 0.001). The amplitude (± se) (<it>α </it>= 0.204 ± 0.04) of simple harmonic curve showed 20.4% difference from the mean to maximum TB cases. The peak to low ratio of adjusted number of TB cases was 1.51 (95% CI: 1.39 – 1.65). The <it>χ</it>²goodness-of-test revealed that there was no significant (<it>P </it>> 0.1) departure of observed frequencies from the fitted simple harmonic curve. Seasonal component explained 55% of the total variation in the proportions of TB cases (100,000) among the migrants.</p> <p>Conclusion</p> <p>This regularity of peak seasonality in TB case detection may prove useful to institute measures that warrant a better attendance of migrants. Public health authorities may consider re-allocation of resources in the period of peak seasonality to minimize the risk of <it>Mycobacterium tuberculosis </it>infection to close contacts in this and comparable settings in the region having similar influx of immigrants from high TB burden countries. Epidemiological surveillance for the TB risk in the migrants in subsequent years and required chemotherapy of detected cases may contribute in global efforts to control this public health menace.</p

Impact of Treadmill Running and Sex on Hippocampal Neurogenesis in the Mouse Model of Amyotrophic Lateral Sclerosis

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a ‘ceiling effect’ of an already heightened basal levels of hippocampal neurogenesis and BDNF expression

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

‘Binge’ drinking in the UK: a social network phenomenon

Agent based model, Social network effect, Simulation methodology,

Elucidating emergence and transmission of multidrug-resistant tuberculosis in treatment experienced patients by whole genome sequencing.

BACKGROUND: Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. METHODS AND FINDINGS: We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort. CONCLUSIONS: Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the emergence of resistance and permit early intervention to avoid onward transmission