Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data
AuthorsRoberts, Stephen A.; orcid: 0000-0002-7477-7731
Brabin, Loretta; orcid: 0000-0003-4478-6503; email: email@example.com
Tinto, Halidou; orcid: 0000-0002-0472-3586
Diallo, Salou; orcid: 0000-0002-1253-4726
Brabin, Bernard; orcid: 0000-0001-6860-2508
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AbstractAbstract: Background: Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. Methods: Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models. Results: Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7–1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15–68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg2, range 4.1–6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001). Conclusions: Our analysis supports preventive treatment of malaria among adolescents 15–19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated.
CitationBMC Public Health, volume 21, issue 1, page 1764
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2021-02-20, accepted 2021-09-16, registration 2021-09-21, pub-electronic 2021-09-27, online 2021-09-27, collection 2021-12
Publication status: Published
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No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database StudyDominguez-Valentin, Mev; orcid: 0000-0001-7856-0057; email: Mev.Dominguez.Valentin@rr-research.no; Plazzer, John-Paul; orcid: 0000-0001-5114-4301; email: firstname.lastname@example.org; Sampson, Julian R.; email: Sampson@cardiff.ac.uk; Engel, Christoph; orcid: 0000-0002-7247-282X; email: email@example.com; Aretz, Stefan; orcid: 0000-0002-5228-1890; email: firstname.lastname@example.org; Jenkins, Mark A.; email: email@example.com; Sunde, Lone; email: firstname.lastname@example.org; Bernstein, Inge; email: email@example.com; Capella, Gabriel; orcid: 0000-0002-4669-7320; email: firstname.lastname@example.org; Balaguer, Francesc; orcid: 0000-0002-0206-0539; email: email@example.com; et al. (MDPI, 2021-06-28)Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.Eales, James M; orcid: 0000-0001-6238-5952; Jiang, Xiao; orcid: 0000-0002-1442-8927; Xu, Xiaoguang; orcid: 0000-0003-4568-1623; Saluja, Sushant; Akbarov, Artur; Cano-Gamez, Eddie; McNulty, Michelle T; Finan, Christopher; orcid: 0000-0002-3319-1937; Guo, Hui; orcid: 0000-0003-0282-6933; Wystrychowski, Wojciech; et al. (2021-05-06)The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?Park, JooYong; email: firstname.lastname@example.org; Choi, Ji-Yeob; email: email@example.com; Choi, Jaesung; email: firstname.lastname@example.org; Chung, Seokang; email: email@example.com; Song, Nan; orcid: 0000-0002-9182-1060; email: firstname.lastname@example.org; Park, Sue K.; orcid: 0000-0001-5002-9707; email: email@example.com; Han, Wonshik; email: firstname.lastname@example.org; Noh, Dong-Young; email: email@example.com; Ahn, Sei-Hyun; email: firstname.lastname@example.org; Lee, Jong Won; email: email@example.com; et al. (MDPI, 2021-05-14)In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.