Transferability of genome-wide associated loci for asthma in African Americans

Objective: Transferability of significantly associated loci or GWAS “hits” adds credibility to genotype-disease associations and provides evidence for generalizability across different ancestral populations. We sought evidence of association of known asthma-associated single nucleotide polymorphisms (SNPs) in an African American population. Methods: Subjects comprised 661 participants (261 asthma cases and 400 controls) from the Howard University Family Study. Forty-eight SNPs previously reported to be associated with asthma by GWAS were selected for testing. We adopted a combined strategy by first adopting an “exact” approach where we looked-up only the reported index SNP. For those index SNPs missing form our dataset, we used a “local” approach that examined all the regional SNPs in LD with the index SNP. Results: Out of the 48 SNPs, our cohort had genotype data available for 27, which were examined for exact replication. Of these, two SNPs were found positively associated with asthma. These included: rs10508372 (OR = 1.567 [95%CI, 1.133-2.167], P = 0.0066) and rs2378383 (OR = 2.147 [95%CI, 1.149–4.013], P = 0.0166), located on chromosomal bands 10p14 and 9q21.31, respectively. Local replication of the remaining 21 loci showed association at two chromosomal loci (9p24.1-rs2381413 and 6p21.32-rs3132947; Bonferroni-corrected P values: 0.0033 and 0.0197, respectively). Of note, multiple SNPs in LD with rs2381413 located upstream of IL33 were significantly associated with asthma. Conclusions: This study has successfully transferred four reported asthma-associated loci in an independent African American population. Identification of several asthma-associated SNPs in the upstream of the IL33, a gene previously implicated in allergic inflammation of asthmatic airway, supports the generalizability of this finding.     

Rotavirus infections and climate variability in Dhaka, Bangladesh: a time-series analysis

Attempts to explain the clear seasonality of rotavirus infections have been made by relating disease incidence to climate factors; however, few studies have disentangled the effects of weather from other factors that might cause seasonality. We investigated the relationships between hospital visits for rotavirus diarrhoea and temperature, humidity and river level, in Dhaka, Bangladesh, using time-series analysis adjusting for other confounding seasonal factors. There was strong evidence for an increase in rotavirus diarrhoea at high temperatures, by 40.2% for each 1 degrees C increase above a threshold (29 degrees C). Relative humidity had a linear inverse relationship with the number of cases of rotavirus diarrhoea. River level, above a threshold (4.8 m), was associated with an increase in cases of rotavirus diarrhoea, by 5.5% per 10-cm river-level rise. Our findings provide evidence that factors associated with high temperature, low humidity and high river-level increase the incidence of rotavirus diarrhoea in Dhaka.     

A comparison of clinical and immunologic features in children and older patients hospitalized with severe cholera in Bangladesh

BACKGROUND:: Infection with Vibrio cholerae induces protection from subsequent severe disease, suggesting that an effective vaccine could be an important preventive strategy. Available vaccines provide less protection against cholera than natural infection, particularly in children. METHODS:: We examined a cohort of 121 children (2 years-12 years of age) and 276 older patients (>12 years of age) hospitalized with cholera in Dhaka, Bangladesh over a 4-year period, to compare clinical features in older patients and children and immune responses to key antigens. RESULTS:: Older patients had more severe disease. Children with cholera were more commonly retinol deficient, while zinc deficiency was equally prevalent in both groups. Children developed higher vibriocidal and serum immune responses to the B subunit of cholera toxin (CTB). In contrast, older patients mounted higher immune responses to 2 other key V. cholerae antigens, the lipopolysaccharide (LPS) and toxin coregulated pilus antigens (TcpA). We compared immune responses following infection with those occurring after receipt of a live, oral vaccine in both children and older patients in Bangladesh, during a similar time period. The response rates for vibriocidal and LPS antibodies were higher after infection than after vaccination. Both vaccinated older patients and children responded poorly to CTB and TcpA. CONCLUSIONS:: Although children developed vigorous vibriocidal and CTB-specific responses following infection, they had lessened responses to LPS and TcpA compared with older patients, as well as lessened responses to vaccination. More studies need to be carried out to determine factors, including micronutrient interventions that can improve responses in children to both natural infection and vaccination.     

Dietary B vitamin intakes and urinary total arsenic concentration in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh

Purpose  

The objective of this analysis was to evaluate the effects of dietary B vitamin intakes on creatinine-adjusted urinary total arsenic concentration among individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar, Bangladesh. Arsenic exposure is a major public health problem in Bangladesh, where nearly 77 million people have been chronically exposed to arsenic through the consumption of naturally contaminated groundwater. Dietary factors influencing the metabolism of ingested arsenic may potentially be important modifiers of the health effects of arsenic in this population.     

Prevalence of tonsillar Actinomyces in children undergoing tonsillectomy for sleep disordered breathing compared with recurrent tonsillitis

Objective

To determine the prevalence of tonsillar actinomycosis in pediatric tonsillectomies performed for sleep disordered breathing (SDB) compared with recurrent infective tonsillitis.

Methods

All tonsillectomy specimens performed in a pediatric otolaryngology practice over a 10-year period were sent to the same pathology laboratory for histological analysis for the prevalence of Actinomyces. A database of 1213 children was generated and analyzed to determine any significant differences in Actinomyces carriage between children with a primary diagnosis of sleep disordered breathing, compared with recurrent tonsillitis. Statistical analysis was performed using a 2 way contingency table, and significance analyzed via chi-squared and Fisher's exact test.

Results

Four hundred and sixty five children aged less than 16 underwent tonsillectomy for recurrent tonsillitis and 748 for SDB. Actinomyces were identified in 68 of the group with recurrent tonsillitis (14.6%) and in 153 of the group with SDB (20.5%). This difference was statistically significant with p = 0.009 on two-tail Fisher's exact test.

Conclusion

There was a statistically significant higher rate of Actinomyces colonization in children undergoing tonsillectomies for SDB compared to recurrent tonsillitis.     

Young children non-immunized against measles: characteristics and programmatic implications

AIM: To examine the presenting characteristics, including nutritional status, of young children without measles immunization and to suggest appropriate public health measures to improve immunization status. METHODS: In this retrospective case-control analysis, we studied 4075 children aged 12-23 mo of either sex, who attended ICDDR,B's Dhaka hospital during 1994-2003. Cases included children who reported to this facility without receiving measles vaccine, and the control children were those who received the vaccine. RESULTS: 3181 of 4075 (78%) children, including 1227 (39%) girls and 1954 (61%) boys, received measles immunization. The proportion of vaccinated children increased from 74% in 1997 to 82% in 2001. Some non-specific effects of measles immunization were observed. Fifty-one per cent of the children without measles immunization were stunted, 76% were underweight, and 48% were wasted. The non-immunized children were twice as likely to be stunted, underweight, and wasted than the immunized children; they were more often dehydrated (some or severe dehydration) (28% vs 22%, p<0.001), required longer duration (>72 h) of hospitalization (15% vs 10%, p<0.001), did not receive vitamin A capsule in the previous 6 mo (56% vs 36%, p<0.001), and had more frequent abnormal lung auscultation indicative of acute lower respiratory tract infections (8% vs 5%, p<0.001). Female children, illiterate mother, lack of vitamin A supplementation, and history of measles were significantly associated with non-immunization against measles after controlling for co-variables. Results were similar when different nutritional indicators (underweight, stunting, or wasting) were added separately to logistic regression models. CONCLUSION: Intervention strategies to enhance immunization coverage in infants should target illiterate mothers and their children, particularly the females and malnourished ones, provide them with measles immunization and vitamin A capsule, and encourage their periodic follow-up visits as part of a preventive nutritional programme.     

Nutritional influence on risk of high blood pressure in Bangladesh: a population-based cross-sectional study

BACKGROUND: The nutritional determinants of hypertension in Bangladesh and other low-income countries are largely unknown. OBJECTIVE: We assessed the associations of general hypertension with nutrient intakes and diet patterns in Bangladesh. DESIGN: This was a cross-sectional analysis of 11 116 participants enrolled in the Health Effects of Arsenic Longitudinal Study in Bangladesh. Dietary intakes were measured by use of a validated food-frequency questionnaire. RESULTS: Three major dietary patterns were identified by using principal component analysis: 1) the "balanced" pattern, which was characterized by rice, some meat, small fish, fruit, and vegetables; 2) the "animal protein" pattern, which was more heavily weighted on meat, milk, poultry, eggs, bread, large fish, and fruit; and 3) the "gourd and root vegetable" pattern, which consisted largely of squashes and root and leafy vegetables. Adjusted prevalence odds ratios for general hypertension in increasing quintiles of balanced pattern scores were 1.00 (reference), 0.81 (95% CI: 0.79, 0.97), 0.82 (0.68, 0.97), 0.79 (0.66, 0.94), and 0.71 (0.59, 0.85) (P for trend < 0.01). Prevalence odds ratios for general hypertension in increasing quintiles of animal protein pattern scores were 1.00 (reference), 1.30 (1.01, 1.52), 1.20 (1.01, 1.47), 1.22 (1.00, 1.44), and 1.21 (1.03, 1.49) (P for trend = 0.23). Markers of high socioeconomic status were positively associated with the animal protein pattern. CONCLUSION: Our findings suggest the importance of dietary patterns in general hypertension in a low-income population undergoing the early stage of the epidemiologic transition.     

ENSO and cholera: a nonstationary link related to climate change?

We present here quantitative evidence for an increased role of interannual climate variability on the temporal dynamics of an infectious disease. The evidence is based on time-series analyses of the relationship between El Ni?o/Southern Oscillation (ENSO) and cholera prevalence in Bangladesh (formerly Bengal) during two different time periods. A strong and consistent signature of ENSO is apparent in the last two decades (1980-2001), while it is weaker and eventually uncorrelated during the first parts of the last century (1893-1920 and 1920-1940, respectively). Concomitant with these changes, the Southern Oscillation Index (SOI) undergoes shifts in its frequency spectrum. These changes include an intensification of the approximately 4-yr cycle during the recent interval as a response to the well documented Pacific basin regime shift of 1976. This change in remote ENSO modulation alone can only partially serve to substantiate the differences observed in cholera. Regional or basin-wide changes possibly linked to global warming must be invoked that seem to facilitate ENSO transmission. For the recent cholera series and during specific time intervals corresponding to local maxima in ENSO, this climate phenomenon accounts for over 70% of disease variance. This strong association is discontinuous in time and can only be captured with a technique designed to isolate transient couplings.     

Progressive multifocal leukoencephalopathy in patients with AIDS: appearance on MR images

Progressive multifocal leukoencephalopathy (PML) is an uncommon demyelinating disease that occurs in immunocompromised patients. The authors evaluated magnetic resonance (MR) images of 10 patients with pathologically proved PML and clinically diagnosed acquired immunodeficiency syndrome (AIDS) to determine the MR characteristics of this disorder. All patients had asymmetric cerebral involvement. Lesions were distributed throughout the brain, including the brain stem and basal ganglia. White matter was affected in all 10 patients; gray matter was also involved in five. In one patient the lesion enlarged and crossed the corpus callosum and contained focal hemorrhage. The authors conclude that, contrary to reported findings on computed tomographic scans, PML in patients with AIDS has a variable appearance on MR images and has many characteristics that differ from those previously thought to be typical on imaging studies.