Renal function of MDR-TB patients treated with kanamycin regimens or concomitantly with antiretroviral agents

SETTING: To compare renal insufficiency among mul-tidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia. DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January–December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test. Renal insufficiency was defined as an eGFR of,60 ml/ min/1.73 m2. Use of KM or TDF and association with renal insufficiency was assessed using Kaplan-Meier plots and Cox proportional hazards analysis. RESULTS: The baseline mean eGFR for the three groups was similar (P ¼ 0.24): 139.3 6 25.6 ml/min for the KM group (n ¼ 68), 131.1 6 25.7 ml/min for the KMþTDF group (n ¼ 44) and 134.2634.4 ml/min for the KMþOther group (n ¼ 23). After 8 months, the values had declined significantly to respectively 104.8 6 37.5 ml/min (P, 0.001), 101.5 6 38.3 ml/min (P, 0.001) and 111.5 6 41.7 ml/min (P ¼ 0.01). Co-treatment with KMþART was associated with an increased risk of renal insufficiency (hazard ratio [HR] 1.8, 95%CI 0.7–4.1, P ¼ 0.20 for KMþTDF, and HR 3.5, 95%CI 1.4–8.2, P ¼ 0.005 for KMþOther ART). CONCLUSION: Renal function declined at a similar rate in MDR-TB patients treated with KM-based regimens compared with patients treated concomitantly with TDF-based or other ART. The risk of renal insufficiency was greater for patients on ART

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. Methods: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Findings: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. Interpretation: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. Funding: WHO, US National Institutes of Health

Evaluation of the involvement of HIV positive patients in the decision to commence antiretroviral therapy at Oshakati Hospital, Namibia

Thesis (MPhil (Industrial Psychology))--University of Stellenbosch, 2009.ENGLISH ABSTRACT: The increase in treatment options for HIV positive people has contributed to an increase in the number of people willing to be tested for HIV since there are now tangible benefits associated with a confirmed HIV positive diagnosis. In Southern Africa the trend towards increased numbers of people who know their HIV status has been more noticeable in women than in men (Muula, et al., 2007), possibly due to the greater health seeking behaviour of women compared to men as well as the access that women have to HIV testing during pregnancy as part of countries' efforts towards preventing mother-to-child transmission of HIV. In Namibia there has been a massive increase in the number of patients commenced on antiretroviral therapy (ART) (MOHSS, 2007). It is important to ensure that increases in the number of patients being started on treatment are accompanied by a proportional improvement in the quality of care being provided to the patients. One important concept that has been promoted in recent years is the Greater Involvement of People Living with HIV/AIDS (GIPA). This concept promotes the inclusion of HIV infected individuals in the decision making process when making decisions regarding the welfare of People Living With HIV (PLHIV). One important caveat specific to ART is the high levels of adherence required for sustained effectiveness of the medicines. Involvement of patients in the design of their treatment has been shown to be a facilitator of adherence to treatment. This study design was a cross-sectional survey whereby a sample of individuals who are registered at Oshakati Communicable Disease Clinic and were receiving ART were interviewed to determine who they perceived to have been the principal decision maker for them to be commenced on ART. The responses were categorized according to the responses from the patients and the frequencies calculated to find the percentage of the patients on ART who considered themselves to have been involved in the decision making process. Having the majority of the patients perceiving themselves as having not been involved in the decision making process was thought to have an important bearing on the counselling which was done prior to starting treatment. This can therefore inform initiatives to improve case management and the involvement of patients in designing their treatment regimens and in making important decisions about their treatment. This ultimately helps to improve the adherence of these patients to their treatment, thereby improving the treatment outcomes and reducing the rate of development of resistance to the antiretroviral medicines (ARVs).AFRIKAANSE OPSOMMING: Agtergrond: Die verhoging in die behandeling opsies vir MIV positiewe mense het bygedra tot verhoogde syfers van die mense gewillig om getoets te word vir MIV, omdat daar voordele is geassosieer met die bevestigde MIV positief diagonose. In Suider- Afrika word die patroon teen die verhoogde syfers of mense wat hulle MIV status ken meer gekenmerk in vroumense as mans; dit is moontlik weens die feit dat vroumense se gedrag teenoor gesondheidraadpleging goed is in vergelyking met die mans, en die vroumense het toegang tot MIV toetse gedurende die swangerskapperiode as deel van die land se poging vir die voorkoming van moeder tot kind transmissie of MIV. In Namibie is daar geweldige verhoogde syfers in pasiente wat met MIV behandeling/terapie begin (ART) het. Die verhoogde syfers of pasiente wat met behandeling begin het moet gesien word in verhouding tot die proporsie van verbetering in kwaliteitsorg voorsien aan pasiente. Een van die belangrikste konsepte wat gedurende afgelope jare bevorder is, is die Betrokkenheid van Mense Leef met MIV wat aanmoedig dat die individuele mense wat met MIV Leef ingesluit word in besluitnemings. Betrokkenheid van pasiente in die gebruik van hulle behandeling is 'n bewys van hulle toewyding tot hulle behandeling. Studiemetode: Die studie uitleg was n "cross-sectional" ondersoek waar geregistreerde individue by Oshakati Communicable Disease Clinic, wie MIV behandeling ontvang, ondervra is om vas te stel wie was hulle hoofbesluitnemer vir hulle om met hierdie MIV behandeling te begin. Die terugvoering is gekategoriseer volgens die bevindings van die pasiente oor hulle betrokkenheid en die besluitneming van hulle behandeling. Uitslae: Die meerderheid van die pasiente (83%) het terugvoering gegee dat hulle tot 'n sekere mate in die besluitneming omtrent hulle behandeling betrokke was. Dit geld vir mans en vroumense. Afsluiting: Die meederheid van die pasiente neem aan dat hulle betrokke is in die proses van die besluitneming, wat 'n positiewe invloed op die toewyding tot hulle medikasie het; en stel voor dat daar wel berading vir pasiente gegee word voor hulle met behandeling begin

Barriers to access to antiretroviral treatment for HIV-positive tuberculosis patients in Windhoek, Namibia

Setting: Namibia faces a high burden of tuberculosis (TB) and HIV-infection. In 2011, 50% of the TB patients were co-infected with HIV. While all patients co-infected with TB and HIV are eligible for antiretroviral treatment (ART), only 54% were reported to have received ART according to national data. Objective: To explore the perspective of healthcare professionals on barriers to access to ART for HIV-positive TB patients. Design: Nine semi-structured qualitative interviews were conducted with healthcare professionals from TB and HIV services in Windhoek in 2012 to investigate access barriers to ART for HIV-positive TB patients in Namibia. Results: Many barriers known from other African countries were also present in Namibia. The barriers rated as most important were: staff shortage (health system level); limited training (healthcare worker level); and fear of stigma and discrimination (patient/community level). Direct treatment costs and limited availability of antiretroviral medication were not observed as barriers. Interference with TB treatment and ART by some Pentecostal churches was revealed as an important barrier that has not yet received sufficient attention. Conclusion: The study identified access barriers to ART for HIV-positive TB patients and their relevance in Namibia. The findings provide evidence for tailored interventions to increase ART-uptake among HIV-positive TB patients

Adverse events and patients' perceived health-related quality of life at the end of multidrug-resistant tuberculosis treatment in Namibia

PURPOSE:The health-related quality of life (HRQoL) of patients completing multidrug-resistant tuberculosis (MDR-TB) treatment in Namibia and whether the occurrence of adverse events influenced patients' rating of their HRQoL was evaluated.PATIENTS AND METHODS:A cross-sectional analytic survey of patients completing or who recently completed MDR-TB treatment was conducted. The patients rated their HRQoL using the simplified Short Form-™ (SF-8) questionnaire consisting of eight Likert-type questions. Three supplemental questions on the adverse events that the patients may have experienced during their MDR-TB treatment were also included. Scoring of HRQoL ratings was norm-based (mean =50, standard deviation =10) ranging from 20 (worst health) to 80 (best health), rather than the conventional 0-100 scores. We evaluated the internal consistency of the scale items using the Cronbach's alpha, performed descriptive analyses, and analyzed the association between the patients' HRQoL scores and adverse events.RESULTS:Overall, 36 patients (20 males, 56%) aged 17-54 years (median =40 years) responded to the questionnaire. The median (range) HRQoL score for the physical component summary was 58.6 (35.3-60.5), while the median score for the mental component summary was 59.3 (26.6-61.9), indicating not-so-high self-rating of health. There was good internal consistency of the scale scores, with a Cronbach's alpha value of >0.80. In all, 32 (89%) of the 36 patients experienced at least one adverse drug event of any severity during their treatment (median events =3, range 1-6), of which none was life-threatening. The occurrence of adverse events was not related to HRQoL scores. For patients reporting zero to two events, the median (range) HRQoL score was 56.8 (44.4-56.8), while for those reporting three or more events, the median score was 55.2 (38.6-56.8); P=0.34 for difference between these scores.CONCLUSION:Patients completing treatment for MDR-TB in Namibia tended to score moderately low on their HRQoL, using the generic SF-8 questionnaire. The occurrence of adverse events did not lead to lower HRQoL scores upon treatment completion

Predictors of tuberculosis treatment success under the DOTS program in Namibia

Objectives: Optimal treatment success rates are critical to end tuberculosis in Namibia. Despite the scale-up of high quality DOTS in Namibia, treatment success falls short of the global target of 90%. Consequently, the objective of this study was to ascertain the predictors of treatment success rates under DOTS in Namibia to provide future direction. Methods: A nation-wide comparative analysis of predictors of treatment success was undertaken. Tuberculosis cases in the electronic tuberculosis register were retrospectively reviewed over a 10-year period, 2004-2016. The patient, programmatic, clinical and treatment predictors of treatment success were determined by multivariate logistic regression modeling using R software. Results: 104,603 TB cases were registered at 300 DOTS sites in 37 districts. The 10-year period treatment success rate was 80%, and varied by region (77.2%-89.2%). The patient’s sex and age were not significant predictors of treatment success. The independent predictors for treatment success as were: Region of DOTS implementation (p=0.001), type of DOT supporter (p<0.001), sputum conversion at 2 months (p=0.013), DOT regimen (p<0.001), cotrimoxazole prophylaxis (p=0.002) and HIV co-infection (p=0.001). Conclusion: Targeted programmatic, clinical and treatment interventions are required to enhance DOTS treatment success in Namibia. These are now ongoing

Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort

BACKGROUND: Amikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing aids, cochlear implants or rehabilitation. Therapeutic drug monitoring and regular audiological assessments may help to prevent or detect the onset of hearing loss, but these services are not always available or affordable in many developing countries. We aimed to compare the cumulative incidence of hearing loss among patients treated for MDR-TB with amikacin or kanamycin-based regimens, and to identify the most-at-risk patients, based on the real-life clinical practice experiences in Namibia. METHODS: We conducted a retrospective cohort study of patients treated with amikacin or kanamycin-based regimens in four public sector MDR-TB treatment sites in Namibia between June 2004 and March 2014. Patients were audiologically assessed as part of clinical care. The study outcome was the occurrence of any hearing loss. Data were manually extracted from patients' treatment records. We compared proportions using the Chi-square test; applied stratified analysis and logistic regression to study the risk of hearing loss and to identify the most-at-risk patients through effect-modification analysis. A P-value < 0.05 was statistically significant. RESULTS: All 353 patients had normal baseline hearing, 46 % were HIV co-infected. Cumulative incidence of any hearing loss was 58 %, which was mostly bilateral (83 %), and mild (32 %), moderate (23 %), moderate-severe (16 %), severe (10 %), or profound (15 %). Patients using amikacin had a greater risk of developing the more severe forms of hearing loss than those using kanamycin (adjusted odds ratio (OR) = 4.0, 95 % CI: 1.5-10.8). Patients co-infected with HIV (OR = 3.4, 95 % CI: 1.1-10.6), males (OR = 4.5, 95 %1.5-13.4) and those with lower baseline body weight (40-59 kg, OR = 2.8, 95 % CI: 1.1-6.8), were most-at-risk of developing hearing loss. CONCLUSION: Amikacin use in the long-term MDR-TB treatment led to a higher risk of occurrence of the more severe forms of hearing loss compared to kanamycin use. Males, patients with low baseline body weight and those co-infected with HIV were most-at-risk. MDR-TB treatment programmes should consider replacing amikacin with kanamycin and strengthen the routine renal, serum therapeutic drug levels and audiometric monitoring in the most-at-risk patients treated with aminoglycosides

Additional file 1: of Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort

Sample audiological assessment form used by the Namibian Ministry of Health and Social Services. (PDF 488 kb