| 1. |
- Chala, A, et al.
(författare)
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Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study
- 2021
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Efavirenz plasma concentration displays wide between-patient variability partly due to pharmacogenetic variation and autoinduction. Pediatric data on efavirenz pharmacokinetics and the relevance of pharmacogenetic variation are scarce, particularly from sub-Saharan Africa, where >90% of HIV-infected children live and population genetic diversity is extensive. We prospectively investigated the short- and long-term effects of efavirenz auto-induction on plasma drug exposure and the influence of pharmacogenetics among HIV-infected Ethiopian children. (2) Method: Treatment-naïve HIV-infected children aged 3–16 years old (n = 111) were enrolled prospectively to initiate efavirenz-based combination antiretroviral therapy (cART). Plasma efavirenz concentrations were quantified at 4, 8, 12, 24, and 48 weeks of cART. Genotyping for CYP2B6, CYP3A5, UGT2B7, ABCB1, and SLCO1B1 common functional variant alleles was performed. (3) Results: The efavirenz plasma concentration reached a peak at two months, declined by the 3rd month, and stabilized thereafter, with no significant difference in geometric mean over time. On average, one-fourth of the children had plasma efavirenz concentrations ≥4 µg/mL. On multivariate analysis, CYP2B6*6 and ABCB1c.3435 C > T genotypes and low pre-treatment low-density lipoprotein (LDL) were significantly associated with higher plasma efavirenz concentration regardless of treatment duration. Duration of cART, sex, age, nutritional status, weight, and SLCO1B, CYP3A5, UGT2B7, and ABCB1 rs3842 genotypes were not significant predictors of efavirenz plasma exposure. (4) Conclusion: Pre-treatment LDL cholesterol and CYP2B6*6 and ABCB1c.3435 C > T genotypes predict efavirenz plasma exposure among HIV-infected children, but treatment-duration-dependent changes in plasma efavirenz exposure due to auto-induction are not statistically significant.
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| 2. |
- Frank, TD, et al.
(författare)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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Ingår i: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Tadesse, BT, et al.
(författare)
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HIV and cART-Associated Dyslipidemia Among HIV-Infected Children
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent dyslipidemia in children is associated with risks of cardiovascular accidents and poor combination antiretroviral therapy (cART) outcome. We report on the first evaluation of prevalence and associations with dyslipidemia due to HIV and cART among HIV-infected Ethiopian children. Methods: 105 cART naïve and 215 treatment experienced HIV-infected children were enrolled from nine HIV centers. Demographic and clinical data, lipid profile, cART type, adherence to and duration on cART were recorded. Total, low density (LDLc) and high density (HDLc) cholesterol values >200 mg/dL, >130 mg/dL, <40 mg/dL, respectively; and/or, triglyceride values >150 mg/dL defined cases of dyslipidemia. Prevalence and predictors of dyslipidemia were compared between the two groups. Results: prevalence of dyslipidemia was significantly higher among cART experienced (70.2%) than treatment naïve (58.1%) children (p = 0.03). Prevalence of low HDLc (40.2% versus 23.4%, p = 0.006) and hypertriglyceridemia (47.2% versus 35.8%, p = 0.02) was higher among cART experienced than naïve children. There was no difference in total hypercholesterolemia and high LDLc levels. Nutrition state was associated with dyslipidemia among cART naïve children (p = 0.01). Conclusion: high prevalence of cART-associated dyslipidemia, particularly low HDLc and hypertriglyceridemia was observed among treatment experienced HIV-infected children. The findings underscore the need for regular follow up of children on cART for lipid abnormalities.
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| 7. |
- Tadesse, BT, et al.
(författare)
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Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia
- 2019
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.
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| 8. |
- Tadesse, BT, et al.
(författare)
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Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study
- 2019
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- There is limited data on virologic outcome and its correlates among HIV-infected children in resource-limited settings. We investigated rate and correlates of virologic outcome among treatment naïve HIV-infected Ethiopian children initiating cART, and were followed prospectively at baseline, 8, 12, 24 and 48 weeks using plasma viral load, clinical examination, laboratory tests and pretreatment HIV drug resistance (PDR) screening. Virologic outcome was assessed using two endpoints–virological suppression defined as having “undetectable” plasma viral load < 150 RNA copies/mL, and rebound defined as viral load ≥150 copies/mL after achieving suppression. Cox Proportional Hazards Regression was employed to assess correlates of outcome. At the end of follow up, virologic outcome was measured for 110 participants. Overall, 94(85.5%) achieved virological suppression, of which 36(38.3%) experienced virologic rebound. At 48 weeks, 9(8.2%) children developed WHO-defined virological treatment failure. Taking tenofovir-containing regimen (Hazard Ratio (HR) 3.1-[95% confidence interval (95%CI) 1.0–9.6], p = 0.049) and absence of pretreatment HIV drug resistance (HR 11.7-[95%CI 1.3–104.2], p = 0.028) were independently associated with earlier virologic suppression. In conclusion, PDR and cART regimen type correlate with rate of virologic suppression which was prominent during the first year of cART initiation. However, the impact of viral rebound in 38.3% of the children needs evaluation.
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| 12. |
- Capeding, MR, et al.
(författare)
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Immune persistence and response to booster dose of Vi-DT vaccine at 27.5 months post-first dose
- 2022
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Ingår i: NPJ vaccines. - : Springer Science and Business Media LLC. - 2059-0105. ; 7:1, s. 12-
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination with typhoid conjugate vaccines (TCV) is a major part of typhoid prevention. However, little is known about long-term immune persistence following vaccination with TCVs. In this phase-2, randomized double-blind trial (NCT03527355), 285 children aged 6–23 months were randomized to one of three groups: (1) the group that received a first dose of Vi polysaccharide conjugated to diphtheria-toxoid (Vi-DT) vaccine followed by an “early booster” at 24 weeks, (2) the group that which received a first dose of Vi-DT followed by a “late booster” at 96 or 110 weeks, and (3) comparator group. Safety and immunogenicity of anti-Vi IgG GMTs were assessed at weeks 0, 4, 24, 28, 60, 96, 110, and 114 since the first dose. Here, we describe persistence of immune responses at weeks 60, 96, 110, and 114 post first dose. The anti-Vi IgG seroconversion rate after 27.5 months of follow-up was 88.16% (95% CI: 79.00, 93.64) in late-booster and 94.76% (95% CI: 86.91, 97.88) in early booster Vi-DT groups (p = 0.081). Whereas anti-Vi IgG GMTs were significantly higher in the early booster group (11.95 [95% CI: 9.65, 14.81]) than prebooster GMTs in the late booster group (5.50 [95% CI: 4.44, 6.80], p < 0.0001). GMT in the late booster group significantly increased to 351.76 (95% CI: 265.01, 466.93) (p < 0.0001) when measured 4 weeks after they received their “late-booster” shot. In conclusion, late booster dosing with Vi-DT at 27.5 months post first dose was safe and elicited robust anti-Vi IgG immune responses. Anti-Vi IgG seroconversion rates were persistently comparable in early and late-booster Vi-DT groups.
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| 18. |
- Escadafal, C, et al.
(författare)
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Bacterial versus non-bacterial infections: a methodology to support use-case-driven product development of diagnostics
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study’s demographics, the causes of fever identified and the performance of selected biomarkers.
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| 22. |
- Gebreyesus, TD, et al.
(författare)
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Prevalence, Intensity, and Correlates of Schistosomiasis and Soil-Transmitted Helminth Infections after Five Rounds of Preventive Chemotherapy among School Children in Southern Ethiopia
- 2020
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from four schools in Wondo Gennet and Hawella Tula districts were screened for Schistosoma mansoni and STHs infection. The overall prevalence of S. mansoni infection was 25.8% (range between schools 11.6% to 54.1%), with light (19.1%), moderate (5.3%), and heavy (1.4%) infection intensities. A total of 61.6% S. mansoni-infected children were STH co-infected. The overall prevalence of STHs infection was 54.7% (range between schools 30.6–71.0%), with moderate-to-heavy intensity infections being 16.3%. Ascaris lumbricoides was the most prevalent 45% (95% CI, 43.5–47) followed by Trichuris trichiura 25.3% (95% CI, 23.8–26.9) and hookworm 6.1% (95% CI, 5.3–7). A total of 33.7% of STHs-infected children had A. lumbricoides and T. trichiura co-infections. S. mansoni infection was significantly associated with school and STHs co-infection (p < 0.001). STH infection was correlated with school and younger age (p < 0.001). Despite repeated PC, S. mansoni and STH infection remain significant health problems, and the WHO target to control schistosomiasis and eliminate STH by 2020 may not be achieved. Intensified control and prevention measures, including drug efficacy surveillance, is recommended.
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| 24. |
- Gebreyesus, TD, et al.
(författare)
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Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:21
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Tidskriftsartikel (refereegranskat)abstract
- Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5–15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5–14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas.
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| 25. |
- Gedefaw, A, et al.
(författare)
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Magnitude of Neural Tube Defects and Associated Risk Factors at Three Teaching Hospitals in Addis Ababa, Ethiopia
- 2018
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2018, s. 4829023-
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Tidskriftsartikel (refereegranskat)abstract
- There is scarcity of data on prevalence of neural tube defects (NTDs) in lower-income countries. Local data are important to understand the real burden of the problem and explore risk factors to design and implement preventive approaches. This study aimed to determine prevalence and risk factors of NTDs. A hospital-based cross-sectional and unmatched case-control study was conducted at three teaching hospitals of Addis Ababa University. NTDs were defined as cases of anencephaly, spina bifida, and encephalocele based on ICD-10 criteria. The prevalence of NTDs was calculated per 10,000 births for both birth and total prevalence. During seven months, we observed 55 cases of NTDs out of 8677 births after 28 weeks of gestation—birth prevalence of 63.4 per 10,000 births (95% confidence interval (CI), 51–77). A total of 115 cases were medically terminated after 12 weeks of gestation. Fifty-six of these terminations (48.7%) were due to NTDs. Thus, total prevalence of NTDs after 12 weeks’ gestation is 126 per 10,000 births (95% CI, 100–150). Planned pregnancy (adjusted odds ratio (aOR), 0.47; 95% CI, 0.24–0.92), male sex (aOR, 0.56; 95% CI, 0.33–0.94), normal or underweight body mass index (aOR, 0.49; 95%, 0.29–0.95), and taking folic acid or multivitamins during first trimester (aOR, 0.47; 95%, 0.23–0.95) were protective of NTDs. However, annual cash family income less than $1,300 USD (aOR, 2.5; 95%, 1.2–5.5), $1,300–1,800 USD (aOR, 2.8; 95%, 1.3–5.8), and $1,801–2,700 USD (aOR, 2.6; 95%, 1.2–5.8) was found to be risk factors compared to income greater than $2,700 USD. The prevalence of NTDs was found to be high in this setting. Comprehensive preventive strategies focused on identified risk factors should be urgently established. More studies on prevention strategies, including folic acid supplementations, should be conducted in the setting.
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