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Association of Stress, Glucocorticoid Receptor, and FK506 Binding Protein Gene Polymorphisms With Internalizing Disorders Among HIV-Infected Children and Adolescents From Kampala and Masaka Districts—Uganda

ABSTRACT: Children and adolescents living with human immunodeficiency virus (CA-HIV) suffer a considerable burden of internalizing disorders (IDs; depressive and anxiety disorders). Environmental and genetic factors have been reported to influence the vulnerability to IDs in western settings; however, their role among African populations remains inadequately explored. We investigated the individual and interactive effects of stress and single-nucleotide polymorphisms within the FK506 binding protein 5 (rs1360780) and glucocorticoid receptor (rs10482605) genes on ID status in a cohort of CA-HIV in Uganda. We genotyped rs10482605 (309 cases and 315 controls) and rs1360780 (350 cases and 335 controls) among CA-HIV with and without IDs using Kompetitive Allele-Specific PCR. Socio-demographic variables, as well as allele and genotype distributions, were compared between cases and controls using chi-square tests. Genotypes were assessed for Hardy–Weinberg equilibrium. Composite indices of recent and chronic stress classes were also generated. A hierarchical cluster analysis was used to generate cutoff points within each of the indices of recent and chronic stress. Logistic regression was used to assess the association between IDs and each of recent stress, chronic stress, and the investigated genotypes. The interaction effect of chronic/recent stress on the association between each of the polymorphisms and IDs was determined using a likelihood ratio test. We observed no significant association between IDs and rs1360780 and rs10482605 polymorphisms within the FKBP5 and glucocorticoid receptor genes, respectively (P > 0.050). Severe recent stress increased the vulnerability to IDs among CA-HIV (P = 0.001). We did not observe any gene–environment effect on vulnerability to IDs in this population. These findings support the currently held opinion that polymorphisms at single genetic loci only contribute a very small effect to the genetic vulnerability to IDs.

SUBMITTER: Owalla T

PROVIDER: S-EPMC8576357 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. Objective: We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). Methods: IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). t-tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. Results: We observed longer rTL among cases of IMDs compared with controls (p < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls (p < 0.001). The same statistical difference was observed when cases and controls were individually analyzed (p < 0.001). We found no significant difference in rTL between cases and controls at 12 months (p = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. Conclusion: rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings.

Project description:BackgroundA high prevalence of suboptimal serum vitamin D has been reported among HIV infected children even in countries with high sunshine abundance throughout the year. Vitamin D is a potent immune modulator of innate and adaptive immune responses. Vitamin D regulates immune responses through the vitamin D receptor on CD4 cells. We aimed to determine the vitamin D status of HIV infected children and factors associated with suboptimal vitamin D.MethodsThis was a cross sectional study. We enrolled children aged between 6 months and 12 years attending an outpatient paediatric HIV clinic. Serum 25-hydroxyvitamin D (25(OH)D) was measured using the electrochemoluminisence method. Suboptimal vitamin D was defined as 25(OH)D <30 ng/ml, vitamin D insufficiency and deficiency were 21-29 ng/ml and <20 ng/ml respectively. Anthropometry, physical exam and medical history were documented. Logistic regression was performed.ResultsWe enrolled 376 children with mean age (sd) 8.05 years (3.03), a median (IQR) duration of ART of 5.9 years (3.2-8.4). Majority of the children (64%) had been exposed to non nucleoside reverse transcriptase inhibitors (NNRTIs). A third were severely immunosuppressed (CD4% ≤15%) at ART initiation. At the time of the study, the majority (89%) were virologically suppressed (VL <1000 copies/ml). Prevalence of 25(OH)D <30 ng/ml was 49 (13%) of 375 participants and 11 (3%) had 25(OH)D <20 ng/ml. Lopinavir/ritonavir regimen was independently associated with 25(OH)D <30 ng/ml; OR 0.27 CI (0.13-0.57), p value-0.002. Serum 25(OH)D <20 ng/ml was associated with CD4 count ≤15% at ART initiation OR 6.55(1.30-32.9), p value-0.023 and use of NNRTIs; OR 10.9(1.22-96.2), p value-0.03.ConclusionWe found a low prevalence of suboptimal vitamin D compared to earlier reports. Severe immunosuppression at ART initiation and use of NNRTIs increases odds of deficiency. Vitamin D supplementation should be considered in severely immunosuppressed children initiating ART.

Project description:BackgroundSyphilis screening can be successfully integrated into antenatal clinics, and potentially avert significant morbidity and mortality to unborn infants. A minority of male partners report for testing and treatment, increasing the likelihood of reinfection. We conducted a qualitative study to understand factors influencing male partners to seek treatment after syphilis notification by their pregnant partners.MethodsA purposeful sample of 54 adults who participated in the STOP (Syphilis Treatment of Partners) study was stratified by gender (24 women, 30 male partners) and enrolled for in-depth interviews which were audio recorded, transcribed, and analyzed using the thematic approach.ResultsThe participants' median age (IQR) was 32 years (25-44), 87% were married, and 57.4% (31/74) had attained secondary education. Fourteen of 22 (63%) female participants reported that they sometimes experienced domestic violence. Male participant's knowledge of syphilis and their perception of their valued role as responsible fathers of an unborn baby facilitated return. Female's fear of partner's violence and poor communication between partners, were barriers against delivery of the notification forms to partners and subsequent treatment of partners. For men, fear of injection pain, perceptions of syphilis as a genetic disease and as a woman's problem, busy work schedules, poor access to good STD services, shared facilities with women in clinics, as well as HIV-related stigma were important barrier factors.ConclusionsThe return to the clinic for treatment of male partners after partner notification by infected pregnant women, was low due to limited knowledge about syphilis, fear of painful injection, fears of domestic violence, lack of communication skills (individual characteristics) and syphilis disease characteristics such as signs and symptoms. This, combined with health services characteristics such as structural barriers that hinder male partner treatment, low access, low capacity, work/time challenges, inadequate laboratory services and low clinic personnel capacity; threatens efforts to eliminate mother-to-child infection of syphilis. Improved public messaging about syphilis, better services, legal and policy frameworks supporting STD notification and treatment in resource-constrained settings are needed for effective STD control.Trial registrationClinicaltrials.gov NCT02262390 ., Date Registered October 8 2014.

Project description:BackgroundHIV/AIDS is a hallmark of immune suppression. Micronutrient deficiencies in diet and recurrent opportunistic infections play major roles in the lives of people living with HIV. Although benefits of providing adequate diet to HIV positive persons are well documented, the demand for key elements still remain unclear in particular settings, especially in low and middle-income countries.MethodsThis was a cross sectional analysis of baseline data collected from HIV-infected adults initiating antiretroviral therapy, and who were enrolled in a multivitamin supplementation trial. A food frequency questionnaire was used and intake were obtained as a product of quantities consumed. Adequacy was calculated as the proportion of Recommended Dietary Allowances (RDA). A chi square test and logistic regression analysis were used at p-value 0.05 to show significant associations.ResultsMean intakes were above minimum requirements for analyzed micronutrients with the exception of Calcium and Iron. Participants who met RDA intakes were as follows: highest (≥ 80%) for Magnesium, Selenium, Zinc and Vitamins B2, B6, B9, C and E; moderate (50% to <80%) for Vitamins B3, and A; and lowest (≤50%) for Iron (30%), Calcium (14.9%), Vitamins B12 and B1. Gender differences in met RDA were observed for Iron, Selenium, Zinc, Vitamins A, B1, B3 and E. In multivariable analyses, nutritional status and CD4 count had no influence on meeting RDA for majority of micronutrients such as magnesium, Selenium, B class vitamins (B1, B2, B3, B6, B9, B12), vitamin (A, C, and E), Zinc and Calcium, but not including iron.Conclusion and global health implicationsDiets consumed by the study participants were low in most protective nutrients (Iron, Calcium, Zinc, Vitamin A, B1, B3, and B12). This deficiency was more common among females than males, and irrespective of BMI or CD 4 count. Findings warrant further investigation on the impact and cost implications for suplementation interventions that target the elements lacking in the diets of people living with HIV in similar low-resourced settings.

Project description:In rabies endemic areas, appropriate management of dog bites is critical in human rabies prevention. Victims must immediately wash bite wound for 15 minutes with water, soap, and a disinfectant before seeking medical care. This study investigated the epidemiology of dog bites and the determinants of compliance to these pre-clinical guidelines requirements among dog bite victims from high rabies-burden areas of Wakiso and Kampala, Uganda. An explanatory sequential mixed-methods study design was used. Quantitative data were collected from 376 dog-bite patients at two healthcare facilities. Qualitative data were also collected through 13 in-depth interviews with patients, healthcare workers, herbalists, and veterinarians. Qualitative data were analyzed using a deductive thematic approach. Generalized linear models were used to determine factors associated with compliance. Nearly half (190, 51%) of the patients were from Wakiso District and 293 (77.9%) had grade II wounds. Most of the wounds (171, 45.5%) were on the legs. Two-thirds of the bites occurred in public places. Only 70 (19%) of the bite patients had complied with pre-clinical guidelines. Nearly half of the patients had applied substances that were not recommended e.g. herbs (47/193), antiseptics (46/193), "black stone" (25/193), and unknown creams (10/193). Factors negatively associated with compliance included: being aged 15 years or older, adjPR = 0.70 (0.47-0.92) and knowing the dog owner, adjPR = 0.65 (0.36-0.93). However, attainment of secondary or higher education, adjPR = 1.76 (1.24-3.79), being in employment, adjPR = 1.48 (1.09-2.31), perception that the dog was sick, adjPR = 1.47 (1.02-2.72) and knowledge about the dog's subsequent victim(s) adjPR = 0.35 (0.17-0.70) were positively associated with compliance. High occurrence of dog bites in public places by free-roaming dogs suggests the need for deliberate promotion of responsible dog ownership. Additionally, targeted health education may be required to improve the low compliance to pre-clinical guidelines.

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Association of Stress, Glucocorticoid Receptor, and FK506 Binding Protein Gene Polymorphisms With Internalizing Disorders Among HIV-Infected Children and Adolescents From Kampala and Masaka Districts—Uganda

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