Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis– a systematic review of global literature with focus on South Africa

IntroductionTuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains. The inclusion of HRQOL PROs in trials and clinical practice can provide additional information beyondclinical and microbiological parameters. Furthermore, HRQOL may be associated with medication adherence. This review focuses on patient-reported HRQOL and its association with medication adherence in TB patients in South Africa.MethodsA comprehensive search strategy was developed focusing on the impact of TB on patient-reported HRQOL,the existence of a conceptual framework of TB-specific HRQOL, determinants of medication adherence and the association of HRQOL with medication adherence. Data were extracted from all identified articles and additionaldata extraction was performed by two independent reviewers with special focus on longitudinal studies in order to understand changes of HRQOL and adherence over time. Research gaps were identified with regard to patient-reported HRQOL and medication adherence.ResultsA total of 66 articles met the eligibility criteria. Ten HRQOL studies and one adherence study used a longitudinal design, none of these in South Africa. A variety of different generic and disease-specific HRQOL measures were identified in the articles. In South Africa four HRQOL and five adherence studies (non-longitudinal) were published. Similar factors (socio-demographic, socio-economic, disease-related, therapy-related and psycho-social aspects) affect HRQOL and adherence. Although standard TB treatment improved all health domains, psychological well-being and social functioning remained impaired in microbiologically cured patients after treatment.ConclusionWhile evidence of TB impact on HRQOL and medication adherence and their association exists, it is verylimited for the South African situation. No valid and reliable TB-specific HRQOL measures were identified in this systematicreview. An assessment of HRQOL in TB patients in South Africa is required as this may assist with improving current disease management programmes, medication adherence and national treatment guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0442-6) contains supplementary material, which is available to authorized users

Drug repurposing and optimisation to improve tuberculosis treatment

Thesis (PhD)--Stellenbosch University, 2021.ENGLISH ABSTRACT: Tuberculosis, a leading infectious cause of mortality, morbidity, and reduced quality of life with loss of income, remains a huge public health burden particularly in resource-limited settings. The golden thread throughout this dissertation, was improving tuberculosis treatment through repurposing and optimisation of existing medicines. For that purpose, we sought to improve our understanding of the pharmacokinetics and pharmacodynamics of selected anti-tuberculosis drugs.AFRIKAANSE OPSOMMING: Tuberkulose, ‘n hoofoorsaak van infeksiesiekte mortaliteit, morbiditeit en verlaagte lewenskwaliteit met verlies aan inkomste, bly ‘n enorme publieke gesondheidslas, veral in omgewings met beperkte hulpbronne. Ons het met hierdie tesis deurlopend beoog om tuberkulose behandeling deur die heroormerking en optimisering van bestaande medisynes te verbeter. Ten einde hierdie doel te bereik, het ons dit ten doel gestel om ons begrip van die farmakokinetika en farmakodinamika van gekose teen-tuberkulose middels te bevorder.Doctora

Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018

CITATION: Du Toit, T., 2019. Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018. BMC Infectious Diseases, 20:900, doi:10.1186/s12879-020-05624-0.The original publication is available at https://bmcinfectdis.biomedcentral.comBackground: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying antirheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province. Methods: A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018. Results: We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10). Conclusion: Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05624-0Publisher's versio

The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis

Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability. Methods: Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily. Meropenem was administered by intravenous infusion over 0.5-1 h. All patients also received oral amoxicillin/clavulanate together with each meropenem dose, and treatments continued daily for 14 days. Intensive plasma pharmacokinetics sampling over 8 h was conducted on the 14th day of the study. Nonlinear mixed-effects modeling was used for data analysis. The best model was chosen based on likelihood metrics, goodness-of-fit plots, and parsimony. Covariates were tested stepwise. Results: A total of 404 concentration measurements from 49 patients were included in the analysis. A two-compartment model parameterized with clearance (CL), inter-compartmental clearance (Q), and central (V1) and peripheral (V2) volumes of distribution fitted the data well. Typical values of CL, Q, V1, and V2 were 11.8 L/h, 3.26 L/h, 14.2 L, and 3.12 L, respectively. The relative standard errors of the parameter estimates ranged from 3.8 to 35.4%. The covariate relations included in the final model were creatinine clearance on CL and allometric scaling with body weight on all disposition parameters. An effect of age on CL as previously reported could not be identified. Conclusion: A two-compartment model described meropenem population pharmacokinetics in patients with pulmonary tuberculosis well. Covariates found to improve model fit were creatinine clearance and body weight but not rifampicin treatment. The final model will be used for an integrated pharmacokinetics/pharmacodynamics analysis linking meropenem exposure to early bactericidal activity

Additional file 1: of Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis– a systematic review of global literature with focus on South Africa

I. Search strategy for identification and selection of relevant studies. II. Quality of reporting check list for longitudinal studies. III. Studies on HRQOL and medication adherence performed in South Africa. (DOCX 682 kb

Determinants of Infant Feeding Practices among Working and Non-working Mothers in Kano, Nigeria

Background: Growth during the first year of life is greater than at any other time after birth. Good nutrition during this period of rapid growth is vital to ensure that infant develops both physically and mentally to the fullest potential.Objectives: This study assessed determinants of feeding practices among working class and non-working class mothers in Kano,  Nigeria.Methodology: Using a comparative cross-sectional study design, interviewer-administered questionnaire was used to collect information from 310 mothers (155 in each group) with their infants' aged 0 – 12 months.Results: Working mothers had a significantly higher level of knowledge of the recommended infant and young child feeding practices (t=4.69, p <0.001) and overall practice performance score was significantly higher among the working group (t= 3.44 p= 0.001). Up to 94.5% working mothers had good knowledge of recommended infant feeding practices compared to 74.0 % of non-working mothers(p=0.001). Haven lost a child, currently being married and vaginal delivery were determinants of appropriate feeding practices among working mothers, while formal education, having five or more children and receiving infant feeding advice were determinants among non-working women.Conclusion: The study found a good knowledge of infant feeding practices among working mothers as compared to the non-working mothers and it also revealed a gap between knowledge and practice of adequate breastfeeding. Context specific health education messages should target both working and non-working class mothers so as to promote, protect and support infant and young child feeding practices in Kano, Nigeria.Keywords: Infant, feeding practices, mothers, breast-feeding, Kan

New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians

Although tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development

Knowledge, risk perception and uptake of COVID-19 vaccination among internally displaced persons in complex humanitarian emergency setting, Northeast Nigeria

Abstract Background Owing to crowded and unsanitary conditions, internally displaced persons (IDPs) have an increased risk of COVID-19 infection. Adoption of COVID-19 preventive measures among this population is premised on accurate information, adequate knowledge, and risk perception. We assessed COVID-19 knowledge and risk perception and investigated the association between risk perception and COVID-19 preventive measures, including vaccination among IDPs in Northeast Nigeria. Methods We conducted a cross-sectional study during July–December 2022 and sampled 2,175 IDPs using stratified sampling. We utilized a 12-point assessment tool to evaluate COVID-19 knowledge. Participants who scored ≥ 6 points were considered to have adequate knowledge. We used a 30-item Risk Behavior Diagnosis Scale to assess COVID-19 risk perception and evaluated each item on a 5-point Likert scale. Participants were divided into risk perception categories by the median of Likert scale scores. We performed weighted logistic regression analysis to identify factors associated with risk perception. Pearson’s chi-squared with Rao-Scott adjustment was used to determine the relationship between risk perception and COVID-19 preventive measures. Results Of 2,175 participants, 55.7% were 18–39 years old, 70.9% were females, and 81.7% had no formal education. Among the IDPs, 32.0% (95% CI: 28.8 – 35.0) were considered to have adequate COVID-19 knowledge, and 51.3% (95% CI: 47.8 – 54.8) perceived COVID-19 risk as high. Moreover, 46.3% (95% CI: 42.8 – 50.0) had received one dose of COVID-19 vaccine, and 33.1% (95% CI: 29.8 – 36.0) received two doses. Adequate knowledge (Adjusted Odds Ratio (AOR) = 2.10, [95% CI: 1.46 – 3.03]) and post-primary education (AOR = 3.20, [95% CI: 1.59 – 6.46]) were associated with risk perception. Furthermore, high risk perception was significantly associated with wearing face masks (χ2 = 106.32, p-value < .001), practicing hand hygiene (χ2 = 162.24, p-value < .001), physical distancing (χ2 = 60.84, p-value < .001) and vaccination uptake (χ2 = 46.85, p-value < .001). Conclusions This study revealed gaps in COVID-19 knowledge, risk perception, and vaccination uptake but demonstrated a significant relationship between risk perception and COVID-19 preventive practices. Health education and risk communication should be intensified to improve knowledge, elicit stronger risk perception, and enhance COVID-19 preventive practices

Drug concentration at the site of disease in children with pulmonary tuberculosis.

BackgroundCurrent TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB.ObjectivesTo determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB.MethodsWe quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions.ResultsIsoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions.ConclusionsDespite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid