Protection against malaria morbidity: Near-fixation of the α-thalassemia gene in a Nepalese population

We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.     

Population Status and Diurnal Behaviour of the Indian Flying Fox <Emphasis Type="Italic">Pteropus giganteus</Emphasis> (Brünnich, 1782) in Kathmandu Valley,Nepal

This study documents the population status and behaviour of the Indian Flying Fox (Pteropus giganteus) at two locations in the temperate environment of the Kathmandu Valley, Nepal. During the five-month study, from 14th July, 2014 to 2nd January, 2015, peak populations were observed in October, 2014 at Sallaghari (1550 individuals) and Keshar Mahal (949 individuals). The behavioural study resulted in 1130 observed events of 10 different behavioural activities at Sallaghari and 1158 events of the same activities at Keshar Mahal. Sleeping, grooming, wing spreading and wing flapping were frequently observed at both study sites. The behaviour of P. giganteus is influenced by the weather and air temperature irrespective of hours of the day and date of observation. Habitat destruction, lack of food, pollution and misconception were the major threats to P. giganteus perceived by local people in course of interviews. Knowledge regarding the population size and behaviours of wildlife species is essential to understand the conservation needs for the survival and management of wild animals and their habitat. This study provides baseline information for two populations of Indian flying fox (P. giganteus) in Kathmandu Valley Nepal.     

A School Health Project Can Uplift the Health Status of School Children in Nepal

BackgroundSchool health is effective in helping students achieve health literacy, enhance their health-related behaviors, and thereby improve their health status. However, in resource-limited countries, evidence is limited to show the impact of school health. We determined the association of the school health and nutrition (SHN) project activities on students’ a) health knowledge, b) hygiene practices, and c) health outcomes, one year after the project completion.MethodsThis is a cross-sectional study conducted among the schools with the SHN project and without the project in four districts of Nepal. We recruited 604 students from six schools in the project group and 648 students from other six schools in the comparison group. We used a self-administered questionnaire to collect the data, and analyzed them using regression models and a structural equation model (SEM).ResultsStudents from the SHN project group reported the decreased odds of worm infestation (AOR = 0.50, 95% CI: 0.34 to 0.75) and diarrhea/ dysentery infection (AOR = 0.67, 95% CI: 0.47 to 0.97) compared to those in the comparison group. Furthermore, the SEM analysis also showed that the students in the project group were more likely to have better health outcomes (β = 0.03, p< 0.05).ConclusionStudents in the SHN project group were more likely to have better health outcomes compared to those in the comparison group, even after one year of the project completion. As it can bring about sustainable changes for students, it should be scaled up in other parts of the country.     

Alcohol Consumption Practices among Married Women of Reproductive Age in Nepal: A Population Based Household Survey

BackgroundAlcohol chemically known as ethanol, causes several health, economic and social consequences across the world. Literatures suggest potential harm of alcohol drinking by pregnant women especially to the fetus and the mother. Despite anumber of significant public health problems related to alcohol consumption, this area has been ignored in Nepal and information at the national level is limited. Thus this study aimed at finding the prevalence of alcohol consumption among married women of reproductive age.MethodsA nationally representative household survey was carried out from April to August 2013 by taking 16 districts across all 15 eco administrative regions. From the selected districts, 86 village development committees and 14 municipalities were selected as primary sampling units using probability proportionate to size, followed by random selection of 3 wards from each primary sampling unit. Finally, 30 households within each ward were selected using systematic random sampling, and one married women of reproductive age from each household. A total of 9000 married women of reproductive age were interviewed using a semi-structured questionnaire, on alcohol consumption practices including environmental factors and socio demographic characteristics and were included in the analysis.ResultsNational prevalence of alcohol consumption ever among married women of reproductive age was 24.7% (95% CI:21.7–28.0), last 12 months 17.9% (95% CI:15.3–20.7) and last 30 days (current drinking) 11.8% (95% CI:9.8–14.1). There was substantial variation among the districts ranging from 2% to 60%. Multivariable analysis suggests women with no education or within formal education, dalit and janajatis ethnicity, whose husbands drink alcohol, who brew alcohol at home and women from mountains were significantly at higher risk of consuming alcohol. Among the women who drank alcohol in last 12 months, a substantial proportion of them drank home brewed alcoholic beverages (95.9%, 95% CI:94.3–97.4).ConclusionAlcohol consumption was common practice among married women of reproductive age in Nepal with variation among the subgroups of population. Thus, further investigation and behavior change communication interventions to reduce alcohol consumption especially among the women with higher risk of drinking is essential.     

Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility

The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway‐based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome‐sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high‐risk women was also identified by pathway‐based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high‐risk and control women, using cell‐based functional assays, drug‐response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell‐based experiments indicate that cell–cell and cell–extracellular matrix adhesion processes seem to be disrupted in non‐malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development.     

Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH)

While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.