Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs

BACKGROUND: Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. METHODS: In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status--new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). RESULTS: Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. CONCLUSIONS: We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem

HFE C282Y and H63D in adults with malignancies in a community medical oncology practice

BACKGROUND: We sought to compare frequencies of HFE C282Y and H63D alleles and associated odds ratios (OR) in 100 consecutive unrelated white adults with malignancy to those in 318 controls. METHODS: Data from patients with more than one malignancy were analyzed according to each primary malignancy. For the present study, OR ≥2.0 or ≤0.5 was defined to be increased or decreased, respectively. RESULTS: There were 110 primary malignancies (52 hematologic neoplasms, 58 carcinomas) in the 100 adult patients. Allele frequencies were similar in patients and controls (C282Y: 0.0850 vs. 0.0896, respectively (OR = 0.9); H63D: 0.1400 vs. 0.1447, respectively (OR = 0.9)). Two patients had hemochromatosis and C282Y homozygosity. With C282Y, increased OR occurred in non-Hodgkin lymphoma, myeloproliferative disorders, and adenocarcinoma of prostate (2.0, 2.8, and 3.4, respectively); OR was decreased in myelodysplasia (0.4). With H63D, increased OR occurred in myeloproliferative disorders and adenocarcinomas of breast and prostate (2.4, 2.0, and 2.0, respectively); OR was decreased in non-Hodgkin lymphoma and B-chronic lymphocytic leukemia (0.5 and 0.4, respectively). CONCLUSIONS: In 100 consecutive adults with malignancy evaluated in a community medical oncology practice, frequencies of HFE C282Y or H63D were similar to those in the general population. This suggests that C282Y or H63D is not associated with an overall increase in cancer risk. However, odds ratios computed in the present study suggest that increased (or decreased) risk for developing specific types of malignancy may be associated with the inheritance of HFE C282Y or H63D. Study of more patients with these specific types of malignancies is needed to determine if trends described herein would remain and yield significant differences

SOD2 Deficient Erythroid Cells Up-Regulate Transferrin Receptor and Down-Regulate Mitochondrial Biogenesis and Metabolism

Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2) show a persistent hemolytic anemia similar to human sideroblastic anemia (SA), including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology., the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis.These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype

Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus

A major barrier to research on Parkinson's disease is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells from patients and differentiate them into neurons affected by disease. Triplication of SNCA, encoding α-synuclein, causes a fully penetrant, aggressive form of Parkinson's disease with dementia. α-Synuclein dysfunction is the critical pathogenic event in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. Here we produce multiple induced pluripotent stem cell lines from an SNCA triplication patient and an unaffected first-degree relative. When these cells are differentiated into midbrain dopaminergic neurons, those from the patient produce double the amount of α-synuclein protein as neurons from the unaffected relative, precisely recapitulating the cause of Parkinson's disease in these individuals. This model represents a new experimental system to identify compounds that reduce levels of α-synuclein, and to investigate the mechanistic basis of neurodegeneration caused by α-synuclein dysfunction

Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi:a modelling study

Background In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. Methods A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. Results Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.</p

Partner relationship satisfaction and maternal emotional distress in early pregnancy

<p>Abstract</p> <p>Background</p> <p>Recognition of maternal emotional distress during pregnancy and the identification of risk factors for this distress are of considerable clinical- and public health importance. The mental health of the mother is important both for herself, and for the physical and psychological health of her children and the welfare of the family. The first aim of the present study was to identify risk factors for maternal emotional distress during pregnancy with special focus on partner relationship satisfaction. The second aim was to assess interaction effects between relationship satisfaction and the main predictors.</p> <p>Methods</p> <p>Pregnant women enrolled in the Norwegian Mother and Child Cohort Study (n = 51,558) completed a questionnaire with questions about maternal emotional distress, relationship satisfaction, and other risk factors. Associations between 37 predictor variables and emotional distress were estimated by multiple linear regression analysis.</p> <p>Results</p> <p>Relationship dissatisfaction was the strongest predictor of maternal emotional distress (β = 0.25). Other predictors were dissatisfaction at work (β = 0.11), somatic disease (β = 0.11), work related stress (β = 0.10) and maternal alcohol problems in the preceding year (β = 0.09). Relationship satisfaction appeared to buffer the effects of frequent moving, somatic disease, maternal smoking, family income, irregular working hours, dissatisfaction at work, work stress, and mother's sick leave (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Dissatisfaction with the partner relationship is a significant predictor of maternal emotional distress in pregnancy. A good partner relationship can have a protective effect against some stressors.</p

Minimal important differences for interpreting health-related quality of life scores from the EORTC QLQ-C30 in lung cancer patients participating in randomized controlled trials

The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in a subset of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) scales, which could be considered as clinically meaningful in patients with non-small-cell lung cancer (NSCLC). WHO performance status (PS) and weight change were used as clinical anchors to determine minimal important differences (MIDs) in HRQOL change scores (range, 0-100) in the EORTC QLQ-C30 scales. Selected distribution-based methods were used for comparison. In a pooled dataset of 812 NSCLC patients undergoing treatment, the values determined to represent the MID depended on whether patients were improving or deteriorating. MID estimates for improvement (based on a one-category change in PS, 5 -aEuro parts per thousand < 20% weight gain) were physical functioning (9, 5); role functioning (14, 7); social functioning (5, 7); global health status (9, 4); fatigue (14, 5); and pain (16, 2). The respective MID estimates for deterioration (based on PS, weight loss) were physical (4, 6); role (5, 5); social (7, 9); global health status (4, 4); fatigue (6, 11); and pain (3, 7). Based on the selected QLQ-C30 scales, the MID may depend upon whether the patients' PS is improving or worsening, but our results are not definitive. The MID estimates for the specified scales can help clinicians and researchers evaluate the significance of changes in HRQOL and assess the value of a health care intervention or compare treatments. The estimates also can be useful in determining sample sizes in the design of future clinical trials