Patient- and delivery-level factors related to acceptance of HIV counseling and testing services among tuberculosis patients in South Africa: a qualitative study with community health workers and program managers

<p>Abstract</p> <p>Background</p> <p>South Africa has a high tuberculosis (TB)-human immunodeficiency virus (HIV) coinfection rate of 73%, yet only 46% of TB patients are tested for HIV. To date, relatively little work has focused on understanding why TB patients may not accept effective services or participate in programs that are readily available in healthcare delivery systems. The objective of the study was to explore barriers to and facilitators of participation in HIV counseling and testing (HCT) among TB patients in the Free State Province, from the perspective of community health workers and program managers who offer services to patients on a daily basis. These two provider groups are positioned to alter the delivery of HCT services in order to improve patient participation and, ultimately, health outcomes.</p> <p>Methods</p> <p>Group discussions and semistructured interviews were conducted with 40 lay counselors, 57 directly observed therapy (DOT) supporters, and 13 TB and HIV/acquired immune deficiency syndrome (AIDS) program managers in the Free State Province between September 2007 and March 2008. Sessions were audio-recorded, transcribed, and thematically analyzed.</p> <p>Results</p> <p>The themes emerging from the focus group discussions and interviews included four main suggested barrier factors: (1) fears of HIV/AIDS, TB-HIV coinfection, death, and stigma; (2) perceived lack of confidentiality of HIV test results; (3) staff shortages and high workload; and (4) poor infrastructure to encourage, monitor, and deliver HCT. The four main facilitating factors emerging from the group and individual interviews were (1) encouragement and motivation by health workers, (2) alleviation of health worker shortages, (3) improved HCT training of professional and lay health workers, and (4) community outreach activities.</p> <p>Conclusions</p> <p>Our findings provide insight into the relatively low acceptance rate of HCT services among TB patients from the perspective of two healthcare workforce groups that play an integral role in the delivery of effective health services and programs. Community health workers and program managers emphasized several patient- and delivery-level factors influencing acceptance of HCT services.</p

Identifying nucleic acid-associated proteins in Mycobacterium smegmatis by mass spectrometry-based proteomics

Abstract Background Transcriptional responses required to maintain cellular homeostasis or to adapt to environmental stress, is in part mediated by several nucleic-acid associated proteins. In this study, we sought to establish an affinity purification-mass spectrometry (AP-MS) approach that would enable the collective identification of nucleic acid-associated proteins in mycobacteria. We hypothesized that targeting the RNA polymerase complex through affinity purification would allow for the identification of RNA- and DNA-associated proteins that not only maintain the bacterial chromosome but also enable transcription and translation. Results AP-MS analysis of the RNA polymerase β-subunit cross-linked to nucleic acids identified 275 putative nucleic acid-associated proteins in the model organism Mycobacterium smegmatis under standard culturing conditions. The AP-MS approach successfully identified proteins that are known to make up the RNA polymerase complex, as well as several other known RNA polymerase complex-associated proteins such as a DNA polymerase, sigma factors, transcriptional regulators, and helicases. Gene ontology enrichment analysis of the identified proteins revealed that this approach selected for proteins with GO terms associated with nucleic acids and cellular metabolism. Importantly, we identified several proteins of unknown function not previously known to be associated with nucleic acids. Validation of several candidate nucleic acid-associated proteins demonstrated for the first time DNA association of ectopically expressed MSMEG_1060, MSMEG_2695 and MSMEG_4306 through affinity purification. Conclusions Effective identification of nucleic acid-associated proteins, which make up the RNA polymerase complex as well as other DNA- and RNA-associated proteins, was facilitated by affinity purification of the RNA polymerase β-subunit in M. smegmatis. The successful identification of several transcriptional regulators suggest that our approach could be sensitive enough to investigate the nucleic acid-associated proteins that maintain cellular functions and mediate transcriptional and translational change in response to environmental stress

Tuberculosis patients' reasons for, and suggestions to address non-uptake of HIV testing: a cross-sectional study in the Free State Province, South Africa

<p>Abstract</p> <p>Background</p> <p>South Africa endorses the global policy shift from primarily client-initiated voluntary counselling and testing (VCT) to routine/provider-initiated testing and counselling (PITC). The reason for this policy shift has been to facilitate uptake of HIV testing amongst at-risk populations in high-prevalence settings. Despite ostensible implementation of routine/PITC, uptake amongst tuberculosis (TB) patients in this country remains a challenge. This study presents the reasons that non-tested TB patients offered for their refusal of HIV testing and reflects on all TB patients' suggestions as to how this situation may be alleviated.</p> <p>Methods</p> <p>In February-March 2008, a cross-sectional survey was conducted amongst 600 TB patients across 61 primary health care facilities in four sub-districts in the Free State. Patient selection was done proportionally to the numbers registered at each facility in 2007. Data were subjected to bivariate tests and content analysis of open-ended questions.</p> <p>Results</p> <p>Almost one-third (32.5%) of the respondents reported that they had not undertaken HIV testing, with the most often offered explanation being that they were '<it>undecided</it>' (37.0%). Other self-reported reasons for non-uptake included: fear (e.g. of testing HIV-positive, 19.0%); perception of being at low risk of HIV infection (13.4%); desire first to deal with TB 'on its own' (12.5%); and because HIV testing had not been offered to them (12.0%). Many patients expressed the need for support and motivation not only from health care workers (33.3%), but also from their significant others (56.6%). Patients further expressed a need for (increased) dissemination of TB-HIV information by health care workers (46.1%).</p> <p>Conclusions</p> <p>Patients did not undergo HIV testing for various patient-/individual-related reasons. Non-uptake of HIV testing was also due to health system limitations such as the non-offer of HIV testing. Other measures may be necessary to supplement routine/provider-initiation of HIV testing. From the TB patient's perspective, there is a need for (improved) dissemination of information on the TB-HIV link. Patients also require (repeated) motivation and support to undergo HIV testing, the onus for which rests not only on the public health authority and health care workers, but also on other people in the patients' social support networks.</p

Identification of d -arabinan-degrading enzymes in mycobacteria

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan. Using one of these isolates with exo-D-galactofuranosidase activity, we generated enriched D-arabinan and used it to identify a strain of Dysgonomonas gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo-D-arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo-D-arabinanases with different preferences for the D-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall

Airway Management in the Paediatric Difficult Intubation Registry: A Propensity Score Matched Analysis of Outcomes Over Time

BACKGROUND: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications. METHODS: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 or 4 view on direct laryngoscopy, (2) limited mouth opening makes direct laryngoscopy impossible, (3) direct laryngoscopy failed in the preceding 6 months, and (4) direct laryngoscopy was deferred due to perceived risk of harm or poor chance of success. We used a 5:1 propensity score match to compare an early cohort from the initial Paediatric Difficult Intubation Registry analysis (August 6, 2012-January 31, 2015, 785 patients, 13 centres) and a current cohort from the Registry (March 4, 2017-March 31, 2023, 3925 patients, 43 centres). The primary outcome was first attempt success rate between cohorts. Success was defined as confirmed endotracheal intubation and assessed by the treating clinician. Secondary outcomes were eventual success rate, number of attempts at intubation, number of attempts with direct laryngoscopy, the incidence of persistence with direct laryngoscopy, use of supplemental oxygen, all complications, and severe complications. FINDINGS: First-attempt success rate was higher in the current cohort (42% vs 32%, OR 1.5 95% CI 1.3-1.8, p \u3c 0.001). In the current cohort, there were fewer attempts (2.2 current vs 2.7 early, regression coefficient -0.5 95% CI -0.6 to -0.4, p \u3c 0.001), fewer attempts with direct laryngoscopy (0.6 current vs 1.0 early, regression coefficient -0.4 95% CI -0.4 to 0.3, p \u3c 0.001), and reduced persistence with direct laryngoscopy beyond two attempts (7.3% current vs 14.1% early, OR 0.5 95% CI 0.4-0.6, p \u3c 0.001). Overall complication rates were similar between cohorts (19% current vs 20% early). Severe complications decreased to 1.8% in the current cohort from 3.2% in the early cohort (OR 0.55 95% CI 0.35-0.87, p = 0.011). Cardiac arrests decreased to 0.8% in the current cohort from 1.8% in the early cohort. We identified persistence with direct laryngoscopy as a potentially modifiable factor associated with severe complications. INTERPRETATION: In the current cohort, children with difficult tracheal intubations underwent fewer intubation attempts, fewer attempts with direct laryngoscopy, and had a nearly 50% reduction in severe complications. As persistence with direct laryngoscopy continues to be associated with severe complications, efforts to limit direct laryngoscopy and promote rapid transition to advanced techniques may enhance patient safety. FUNDING: None

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda's human African trypanosomiasis elimination programme

BACKGROUND: The recent development of rapid diagnostic tests (RDTs) for human African trypanosomiasis (HAT) enables elimination programmes to decentralise serological screening services to frontline health facilities. However, patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases. Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions. This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile, Uganda. METHODS: Between August 2013 and June 2015, 85% (295/346) people who screened RDT-positive were examined by microscopy at least once; 10 cases were detected. We interviewed 20 RDT-positive suspects who had not completed referral (16 who had not presented for their first microscopy examination, and 4 who had not returned for a second to dismiss them as cases after receiving discordant [RDT-positive, but microscopy-negative results]). Interviews were analysed thematically to examine experiences of each step of the referral process. RESULTS: Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample. Most patients were unaware they were tested for HAT until receiving results, and some did not know they had screened positive. While HAT testing and treatment is free, anticipated costs for transportation and ancillary health services fees deterred many. Most expected a positive RDT result would lead to HAT treatment. RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers. For the four individuals who missed their second examination, complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given. CONCLUSIONS: An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations. In Uganda, a key structural weakness was poor provider communication about the possibility of discordant HAT test results, which is the most common outcome for serological RDT suspects in a HAT elimination programme. Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes

The research landscape of tuberous sclerosis complex–associated neuropsychiatric disorders (TAND)—a comprehensive scoping review

Background Tuberous sclerosis complex (TSC)–associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. Methods The study was conducted in accordance with stages outlined within the Arksey and O’Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. Results Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low–middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder–like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). Conclusions Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified

Physical and emotional health outcomes after 12 months of public-sector antiretroviral treatment in the Free State Province of South Africa: a longitudinal study using structural equation modelling

<p>Abstract</p> <p>Background</p> <p>African and Asian cohort studies have demonstrated the clinical efficacy of antiretroviral treatment (ART) in resource-limited settings. However, reports of the long-term changes in the physical and emotional quality of life (QoL) of patients on ART in these settings are still scarce. In this study, we assessed the physical and emotional QoL after six and 12 months of ART of a sample of 268 patients enrolled in South Africa's public-sector ART programme. The study also tested the impact of the adverse effects of medication on patients' physical and emotional QoL.</p> <p>Methods</p> <p>A stratified random sample of 268 patients undergoing ART was interviewed at baseline (< 6 months ART) and follow-up (< 12 months ART). A model of the relationships between the duration of ART, the adverse effects of medication, and physical and emotional QoL (measured using EUROQOL-5D) was tested using structural equation modelling.</p> <p>Results</p> <p>The improved physical and emotional QoL shown at baseline was sustained over the 12-month study period, because treatment duration was not significantly associated with changes in the patients' QoL. Physical QoL significantly and positively influenced the patients' emotional QoL (subjective well-being [SWB]) (β = 0.33, <it>P </it>< 0.01). Longitudinal data showed that patients reported significantly fewer adverse effects at follow-up than at baseline (β = -0.38, <it>P </it>< 0.001) and that these adverse effects negatively influenced physical (β = -0.27, <it>P </it>< 0.01) and emotional QoL (β = -0.15, <it>P </it>< 0.05).</p> <p>Conclusion</p> <p>This study provides evidence that the South African public-sector ART programme is effective in delivering sustained improvement in patient well-being. However, the results should encourage clinicians and lay health workers to be vigilant regarding the adverse effects of treatment, because they can seriously affect physical and emotional QoL.</p

Patient satisfaction with antiretroviral services at primary health-care facilities in the Free State, South Africa – a two-year study using four waves of cross-sectional data

<p>Abstract</p> <p>Background</p> <p>The study's first objective was to determine the levels of patient satisfaction with services at antiretroviral treatment (ART) assessment sites. Differences in patient satisfaction with several aspects of service over time and among health districts were measured. The second objective was to examine the association between human resource shortages and levels of patient satisfaction with services.</p> <p>Methods</p> <p>Four cross-sectional waves of data were collected from a random sample of 975 patients enrolled in the Free State's public-sector ART programme. One-way analysis of variance (ANOVA) with the Bonferroni adjustment for multiple comparisons was used to assess the differences in patient satisfaction among the Province's five districts and among the four waves of data. Correlation coefficient analysis using Pearson's <it>r </it>was used to assess the association between ART nurse vacancy rates and patient satisfaction with the services provided by nurses over time.</p> <p>Results</p> <p>With respect to both general services and the services provided by nurses, our results indicate high overall satisfaction among Free State patients receiving public-sector ART. However, our data present a less positive picture of patient satisfaction with waiting times. Patients in Fezile Dabi District were generally slightly dissatisfied with the waiting times at their assessment sites. In fact, waiting times at assessment sites were the most important predictor of discontent among ART patients. Significant geographical (<it>P </it>< 0.001) and temporal differences (<it>P </it>< 0.005) were observed in these three aspects of patient satisfaction. Patients were most satisfied in Thabo Mofutsanyana District and least satisfied in Motheo District. Patients in Fezile Dabi District were generally slightly dissatisfied with the waiting times at their assessment sites. Finally, our analysis revealed a strong negative association (<it>r </it>= -0.438, <it>P </it>< 0.001) between nurse vacancy rates and mean satisfaction levels with services performed by nurses at baseline. Patients attending facilities with high professional nurse vacancy rates reported significantly less satisfaction with nurses' services than did those attending facilities with fewer vacant nursing posts.</p> <p>Conclusion</p> <p>Collectively, our findings show high levels of patient satisfaction with ART-related services, but also confirm claims by other studies, which have identified human resource shortages as the most important obstacle to a successful South African AIDS strategy.</p