Health care seeking patterns of rifampicin-resistant tuberculosis patients in Harare, Zimbabwe: A prospective cohort study.
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ABSTRACT: Background
Delays in seeking and accessing treatment for rifampicin-resistant tuberculosis (RR-TB) and multi-drug resistant (MDR-TB) are major impediments to TB control in high-burden, resource-limited settings.Method
We prospectively determined health-seeking behavioural patterns and associations with treatment outcomes and costs among 68 RR-TB patients attending conveniently selected facilities in a decentralised system in Harare, Zimbabwe.Results
From initial symptoms to initiation of effective treatment, patients made a median number of three health care visits (IQR 2-4 visits) at a median cost of 13% (IQR 6-31%) of their total annual household income (mean cost, US$410). Cumulatively, RR-TB patients most frequently first visited private facilities, i.e., private pharmacies (30%) and other private health care providers (24%) combined. Median patient delay was 26 days (IQR 14-42 days); median health system delay was 97 days (IQR 30-215 days) and median total delay from symptom onset to initiation of effective treatment was 132 days (IQR 51-287 days). The majority of patients (88%) attributed initial delay in seeking care to "not feeling sick enough." Total delay, total cost and number of health care visits were not associated with treatment or clinical outcomes, though our study was not adequately powered for these determinations.Conclusions
Despite the public availability of rapid molecular TB tests, patients experienced significant delays and high costs in accessing RR-TB treatment. Active case finding, integration of private health care providers and enhanced service delivery may reduce treatment delay and TB associated costs.
SUBMITTER: Tadokera R
PROVIDER: S-EPMC8284678 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Zimbabwe is one of the thirty countries globally with a high burden of multidrug-resistant tuberculosis (TB) or rifampicin-resistant TB (MDR/RR-TB). Since 2010, patients diagnosed with MDR/RR-TB are being treated with 20-24 months of standardized second-line drugs (SLDs). The profile, management and factors associated with unfavourable treatment outcomes of MDR/RR TB have not been systematically evaluated in Zimbabwe. OBJECTIVE:To assess treatment outcomes and factors associated with unfavourable outcomes among MDR/RR-TB patients registered and treated under the National Tuberculosis Programme in all the district hospitals and urban healthcare facilities in Zimbabwe between January 2010 and December 2015. METHODS:A cohort study using routinely collected programme data. The 'death', 'loss to follow-up' (LTFU), 'failure' and 'not evaluated' were considered as "unfavourable outcome". A generalized linear model with a log-link and binomial distribution or a Poisson distribution with robust error variances were used to assess factors associated with "unfavourable outcome". The unadjusted and adjusted relative risks were calculated as a measure of association. A ?value< 0.05 was considered statistically significant. RESULTS:Of the 473 patients in the study, the median age was 34 years [interquartile range, 29-42] and 230 (49%) were males. There were 352 (74%) patients co-infected with HIV, of whom 321 (91%) were on antiretroviral therapy (ART). Severe adverse events (SAEs) were recorded in 118 (25%) patients; mostly hearing impairments (70%) and psychosis (11%). Overall, 184 (39%) patients had 'unfavourable' treatment outcomes [125 (26%) were deaths, 39 (8%) were lost to follow-up, 4 (<1%) were failures and 16 (3%) not evaluated]. Being co-infected with HIV but not on ART [adjusted relative risk (aRR) = 2.60; 95% CI: 1.33-5.09] was independently associated with unfavourable treatment outcomes. CONCLUSION:The high unfavourable treatment outcomes among MDR/RR-TB patients on standardized SLDs were coupled with a high occurrence of SAEs in this predominantly HIV co-infected cohort. Switching to individualized all oral shorter treatment regimens should be considered to limit SAEs and improve treatment outcomes. Improving the ART uptake and timeliness of ART initiation can reduce unfavourable outcomes.
| S-EPMC7192497 | biostudies-literature
Project description:BackgroundData on long-term outcomes of patients receiving antiretroviral therapy (ART) in sub-Saharan Africa are few. We describe outcomes of patients commenced on ART at Newlands Clinic between 2004 and 2006 after ?10 years of comprehensive care including, psychosocial, adherence and food support.MethodsIn this retrospective cohort study, patient data from an electronic medical record collected during routine care were analysed. We describe baseline characteristics, virological and clinical outcomes, attrition rates, and treatment adverse effects until November 2016. We defined virological suppression as viral load <50 copies/ml and virological failure as >1000 copies/ml after ?6 months of ART.ResultsWe analysed data for 605 patients (67% female) who commenced ART, and were followed-up for 5819 person-years (median: 10.7 years, IQR: 10.1-11.4). Median age at ART initiation was 34 years (IQR: 17-42). Pre-ART, 129 (21.3%) patients had history of pulmonary tuberculosis (PTB). In care, 66 (11%) developed PTB, and 24 (4%) developed extrapulmonary tuberculosis. 385 (63.6%) patients experienced ?1 adverse event, the most frequent being stavudine-induced peripheral neuropathy (n = 252, 41.7%). At database closure on 14 November 2016, 474 (78.3%) patients were still in care, 428 (90.3%) being virologically suppressed, and 21 (4.4%) failing. While 483 (79.8%) remained on first line, 122 (20.2%) were switched to second line ART. Fifty-nine patients (9.8%) were transferred to other ART facilities, 45 (7.4%) were lost to follow-up, 25 (4.1%) died, and two stopped ART.ConclusionComprehensive HIV care can result in low mortality, high retention in care and virologic suppression rates in resource limited settings.
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| S-EPMC8406724 | biostudies-literature
Project description:Country-specific interventions targeting high-risk groups are necessary for a global reduction in Tuberculosis (TB)/HIV burden. We analyzed the data of 13,802 TB cases diagnosed in Harare, Zimbabwe, during 2013-2017. Pearson's chi-square tests and multivariate logistic regression models were used to identify patient characteristics significantly associated with TB/HIV coinfection. Of the 13,802 TB cases analyzed, 9,725 (70.5%) were HIV positive. A significantly higher odds of having TB/HIV coinfection diagnosis was found among females, patients aged 25-64 years, previously treated cases, and acid-fast bacillus sputum smear-negative cases. Compared with nondisseminated pulmonary TB, miliary TB (adjusted odds ratio [aOR]: 1.469, 95% CI: 1.071, 2.015) and TB meningitis (aOR: 1.715, 95% CI: 1.074, 2.736) both had a significantly higher odds for TB/HIV coinfection, whereas pleural TB (aOR 0.420, 95% CI: 0.354, 0.497) and all other extrapulmonary TB (EPTB) (aOR: 0.606, 95% CI: 0.516 0.712) were significantly less likely to have TB/HIV coinfection. The risk for TB/HIV coinfection varied significantly by patients' sociodemographic and clinical characteristics in Harare. Our finding that different forms of EPTB have different relationships with HIV coinfection has extended the knowledge base about clinical markers for TB/HIV coinfection which can lead to a greater public health impact on eliminating TB/HIV infection.
| S-EPMC7356430 | biostudies-literature
Project description:RationaleCentral dogma suggests that rifampicin resistance in Mycobacterium tuberculosis develops solely through rpoB gene mutations.ObjectiveTo determine whether rifampicin induces efflux pumps activation in rifampicin resistant M. tuberculosis strains thereby defining rifampicin resistance levels and reducing ofloxacin susceptibility.MethodsRifampicin and/or ofloxacin minimum inhibitory concentrations (MICs) were determined in rifampicin resistant strains by culture in BACTEC 12B medium. Verapamil and reserpine were included to determine their effect on rifampicin and ofloxacin susceptibility. RT-qPCR was applied to assess expression of efflux pump/transporter genes after rifampicin exposure. To determine whether verapamil could restore susceptibility to first-line drugs, BALB/c mice were infected with a MDR-TB strain and treated with first-line drugs with/without verapamil.Measurements and main findingsRifampicin MICs varied independently of rpoB mutation and genetic background. Addition reserpine and verapamil significantly restored rifampicin susceptibility (p = 0.0000). RT-qPCR demonstrated that rifampicin induced differential expression of efflux/transporter genes in MDR-TB isolates. Incubation of rifampicin mono-resistant strains in rifampicin (2 μg/ml) for 7 days induced ofloxacin resistance (MIC > 2 μg/ml) in strains with an rpoB531 mutation. Ofloxacin susceptibility was restored by exposure to efflux pump inhibitors. Studies in BALB/c mice showed that verapamil in combination with first-line drugs significantly reduced pulmonary CFUs after 1 and 2 months treatment (p < 0.05).ConclusionExposure of rifampicin resistant M. tuberculosis strains to rifampicin can potentially compromise the efficacy of the second-line treatment regimens containing ofloxacin, thereby emphasising the need for rapid diagnostics to guide treatment. Efflux pump inhibitors have the potential to improve the efficacy of anti-tuberculosis drug treatment.
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Project description:BACKGROUND:Cervical cancer is a major cause of morbidity and mortality among women yet access to treatment and care remains a huge challenge in Zimbabwe. The objective of this study was to investigate health system constraints affecting engagement into treatment and care by women with cervical cancer in Harare, Zimbabwe. METHODS:A sequential explanatory mixed methods design was used for this study. Phase 1 comprised of two surveys namely: patient and health worker surveys with sample sizes of 134 and 78 participants respectively. Validated structured questionnaires programmed in Android tablet with SurveytoGo software were used for data collection during the surveys. Univariate analyses were conducted using STATA® version 14 to generate descriptive statistics. In phase 2, 16 in-depth interviews, 20 key informant interviews and 6 focus groups were conducted to explain survey results. Participants were purposively selected and sample sizes were informed by saturation principle. Participants in phase 1 and 2 were different. English transcripts were manually coded line by line in Dedoose software using the thematic codes that had been established from the survey data. The final codes were used to support and explain the survey data at the interpretation stages. RESULTS:Health system constraints identified in surveys were: limited or lack of training for health workers, weakness of surveillance system for cervical cancer, limited access to treatment and care, inadequate health workers, reliance of patients on out-of-pocket funding for treatment services, lack of back-up for major equipment. Qualitative inquiry revealed the following barriers to treatment and care: high costs of treatment and care, lack of knowledge about cervical cancer and bad attitudes of health workers, few screening and treating centres located mostly in urban areas, lack of clear referral system resulting in bureaucratic processes, and limited screening and treating capacities in health facilities due to lack of resources. CONCLUSION:The results of this study show that health system and its organization present barriers to access of cervical cancer treatment and care among women. Strong political will, mobilization of resources both domestically and from partners in addition to sound policies are imperative to address key health system challenges.
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Project description:IntroductionThe scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a range of morbidities due to chronic HIV infection and its treatment. Impaired linear growth (stunting) is a common manifestation, affecting up to 50% of children. However, the effect of HIV on bone and muscle development during adolescent growth is not well characterised. Given the close link between pubertal timing and musculoskeletal development, any impairments in adolescence are likely to impact on future adult musculoskeletal health. We hypothesise that bone and muscle mass accrual in CWH is reduced, putting them at risk of reduced bone mineral density (BMD) and muscle function and increasing fracture risk. This study aims to determine the impact of HIV on BMD and muscle function in peripubertal children on ART in Zimbabwe.Methods and analysisChildren with (n=300) and without HIV (n=300), aged 8-16 years, established on ART, will be recruited into a frequency-matched prospective cohort study and compared. Musculoskeletal assessments including dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, grip strength and standing long jump will be conducted at baseline and after 1?year. Linear regression will be used to estimate mean size-adjusted bone density and Z-scores by HIV status (ie, total-body less-head bone mineral content for lean mass adjusted for height and lumbar spine bone mineral apparent density. The prevalence of low size-adjusted BMD (ie, Z-scores <-2) will also be determined.Ethics and disseminationEthical approval for this study has been granted by the Medical Research Council of Zimbabwe and the London School of Hygiene and Tropical Medicine Ethics Committee. Baseline and longitudinal analyses will be published in peer-reviewed journals and disseminated to research communities.
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Project description:In communities with low rates of institutional delivery, little data exist on care-seeking behavior for potentially life-threatening obstetric complications. In this analysis, we sought to describe care-seeking patterns for self-reported complications and near misses in rural Bangladesh and to identify factors associated with care seeking for these conditions.Utilizing data from a community-randomized controlled trial enrolling 42,214 pregnant women between 2007 and 2011, we used multivariable multinomial logistic regression to explore the association of demographic and socioeconomic factors, perceived need, and service availability with care seeking for obstetric complications or near misses. We also used multivariable multinomial logistic regression to analyze the factors associated with care seeking by type of obstetric complication (eclampsia, sepsis, hemorrhage, and obstructed labor).Out of 9,576 women with data on care seeking for obstetric complications, 77% sought any care, with 29% (n = 2,150) visiting at least one formal provider and 70% (n = 5,149) visiting informal providers only. The proportion of women seeking at least one formal provider was highest among women reporting eclampsia (57%), followed by hemorrhage (28%), obstructed labor (22%), and sepsis (17%) (p < 0.001). In multivariable analyses, socioeconomic factors such as living in a household from the highest wealth quartile (Relative Risk Ratio of 1.49; 95% CI of [1.33-1.73]), women's literacy (RRR of 1.21; 95% CI of [1.05-1.42]), and women's employment (RRR of 1.10; 95% CI of [1.01-1.18]) were significantly associated with care seeking from formal providers. Service factors including living less than 10 kilometers from a health facility (RRR of 1.16; 95% CI of [1.05-1.28]) and facility availability of comprehensive obstetric services (RRR of 1.25; 95% CI of 1.04-1.36) were also significantly associated with seeking care from formal providers.While the majority of women reporting obstetric complications sought care, less than a third visited health facilities. Improvements in socioeconomic factors such as maternal literacy, coupled with improved geographic access and service availability, may increase care seeking from formal facilities. Enhancing community awareness on symptoms of hemorrhage, sepsis, and obstructed labor and their consequences may promote care seeking for obstetric complications in rural Bangladesh.NCT00860470 .
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Project description:INTRODUCTION:Key to pharmacovigilance is spontaneously reporting all Adverse Drug Reactions (ADR) during post-market surveillance. This facilitates the identification and evaluation of previously unreported ADR's, acknowledging the trade-off between benefits and potential harm of medications. Only 41% Antiretroviral (ARV) ADR's documented in Harare city clinical records for January to December 2016 were reported to Medicines Control Authority of Zimbabwe (MCAZ). We investigated reasons contributing to underreporting of ARV ADR's in Harare city. METHODS:A descriptive cross-sectional study and the Centers for Disease Control (CDC) guided surveillance evaluation was conducted. Two hospitals were purposively included. Seventeen health facilities and 52 health workers were randomly selected. Interviewer-administered questionnaires, key informant interviews and WHO pharmacovigilance checklists were used to collect data. Likert scales were applied to draw inferences and Epi info 7 used to generate frequencies and proportions. RESULTS:Of the 52 participants, 32 (61.5%) distinguished the ARV ADR defining criteria. Twenty-nine (55.8%) knew system's purpose whilst 28 (53.8%) knew the reporting process. Knowledge scored average on the 5-point-Likert scale. Thirty-eight (73.1%) participants identified ARV ADR's following client complaints and nine (1.3%) enquired clients' medication response. Forty-six (88.5%) cited non-feedback from MCAZ for underreporting. Inadequate ARV ADR identification skills were cited by 21 (40.4%) participants. Reporting forms were available in five (26.3%) facilities and reports were generated from hospitals only. Forty-two (90.6%) clinicians made therapeutic decisions from ARV ADR's. Averaged usefulness score was 4, on the 5-point-Likert scale. All 642 generated signals were committed to Vigiflow by MCAZ, reflecting a case detection rate of 4/ 100 000. Data quality was 0.75-1.0 (WHO) and all reports were causally assessed. CONCLUSION:The pharmacovigilance system was useful, simple, and acceptable despite being unstable, not representative and not sensitive. It was threatened by suboptimal health worker knowledge, weak detection strategies and referral policy preventing ARV ADR identification by person place and time. Revisiting local policy, advocacy, communication and health worker orientation might improve pharmacovigilance performance in Harare city.
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Project description:Tuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan.
| S-EPMC8270973 | biostudies-literature