Treatment initiation among tuberculosis patients: the role of short message service (SMS) technology and Ward-based outreach teams (WBOTs).

BACKGROUND: In South Africa, tuberculosis (TB) is a public health problem with treatment initiation failure rates varying between 14.9 and 25%. Lack of proper provider/patient communication on next steps after testing, not being aware that results are ready; and other competing priorities are some of the reasons for this failure. We aimed to assess the effectiveness of Short Message Service (SMS) technology and ward-based outreach teams (WBOTs) in improving TB treatment initiation. A 3-arm randomized controlled trial (Standard of care-SOC, SMS technology or WBOTs) was conducted between September 2018 and April 2020. Newly diagnosed TB patients randomly allocated to SMS and WBOTs groups were sent reminder messages (text message or paper slip respectively) that results were ready. Due to unforeseen challenges (financial and impact of the COVID 19 pandemic), implementation was only in two of the eight clinics planned. RESULTS: 314 TB patients were assigned to one of three groups (SOC = 104, WBOTs = 105, and SMS = 105). Chi-square tests were used to compare proportions starting treatment (primary outcome). More patients in the SMS group (92/105; 88%) initiated treatment than in the SOC group (81/104; 78%), although this difference did not reach statistical significance (P = 0.062). The time to treatment initiation was significantly shorter in the SMS group than in the SOC group (P < 0.001). The proportions of patients initiated on treatment in the WBOTs group (45/62; 73%) and in the SOC group (44/61; 72%) were similar (P = 0.956). The times to treatment initiation for these two groups were also similar. The 3 group analysis yielded similar proportions initiated on treatment (P = 0.048 for SMS/SOC comparison and P = 0.956 for WBOTs/SOC comparison) but analysis of times to treatment initiation yielded some variations. CONCLUSION: Reminder SMS messages sent to newly diagnosed TB patients improved the time to treatment initiation. Further research is required to show effect of the WBOTs intervention. TRIAL REGISTRATION: Retrospectively registered with the Pan African Clinical Trial Registry ( PACTR202101914895981 ). The trial was registered with the Pan African Clinical Trial Registry on 25 January, 2021 (ref: PACTR202101914895981 ; https://pactr.samrc.ac.za ). The registration was retrospective due to an oversight. Nevertheless, the protocol details outlined in our ethics application were strictly adhered to.

Initial loss to follow up of tuberculosis patients in South Africa: perspectives of program managers.

BACKGROUND: Tuberculosis (TB) remains a serious public health problem in South Africa. Initial loss to follow up (LTFU) rates among TB patients are high, varying between 14.9 and 22.5%. From the perspective of patients, documented reasons for this include poor communication between patient and staff after testing, not being aware that results are ready and other competing priorities such as preference to go to work as opposed to seeking healthcare. Ward-based Outreach Teams (WBOTs) routinely conduct home visits to ensure adherence to medication for various conditions including TB. We explored reasons for TB initial loss to follow up from the perspectives of TB program managers and WBOT program managers, with a focus on the WBOT's (potential) role in reducing initial LTFU, in particular. METHODS: Key informant interviews with five WBOT program managers and four TB program managers were conducted. The interviews were audio-recorded, then transcribed and exported to NVivo 11 software for coding. A hybrid analytic approach consisting of both inductive and deductive coding was used to identify themes. RESULTS: The age of the nine managers ranged between 28 and 52 years old, of which two were male. They had been in their current position for between 2 to 12 years. Prior to treatment initiation, WBOTs screen household members for TB and refer them for TB testing if need be, but integration of the two programs is emphasized only after TB treatment has been initiated. Counseling of patients testing for TB is not guaranteed due to frequent staff rotations and staff shortages. Participants reported that possible dissatisfaction with services as well as stigma associated with the TB diagnosis could explain loss to follow up prior to treatment initiation. CONCLUSION: Program managers view health system related factors such as staff rotations, poor communication with patients and lack of counseling as contributing to the problem of initial LTFU among TB patients. The integration of the WBOT and TB programs is limited to referring suspected cases for testing and patients already on treatment.

Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus-1.

BACKGROUND: The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1-infected individuals are likely to progress to active disease is unknown. METHODS: Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1-infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations. RESULTS: Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly. CONCLUSIONS: Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.

Initial loss to follow up among tuberculosis patients: the role of Ward-Based Outreach Teams and short message service (SMS) technology (research proposal).

INTRODUCTION: Tuberculosis (TB) is a problem in South Africa. Initial loss to follow up (LTFU) among TB patients is high varying between 14.9 and 18%. Some of the reasons for this are: lack of proper communication between patient and staff on next steps after testing, not aware that results are ready; and other competing priorities. Receiving reminder messages that result is ready is an intervention that can be explored to reduce initial LTFU. This can be through either receiving a note from the Ward-Based Outreach Teams (WBOTs) or via short message service (SMS) advising the patient to collect test result at the facility. This proposal aims to assess the effectiveness of WBOTs or SMS technology in reducing TB initial LTFU. METHODS: This will be a mixed methods approach. In depth interviews with WBOT Managers and TB Program Managers will be conducted. Focus group discussions with WBOT members will also be conducted. Two interventions (enhanced WBOTs/SMS technology) will be tested using a 3 arm randomized controlled trial (standard of care, SMS technology or enhanced WBOTs). The WBOTs will deliver paper note reminders while SMS intervention will entail sending reminder SMS messages to patients as soon as TB results are ready.

Microbiologically Confirmed Tuberculosis: Factors Associated with Pre-Treatment Loss to Follow-Up, and Time to Treatment Initiation.

BACKGROUND: The impact of new diagnostics on pre-treatment loss to follow up (Pre-treatment LTFU) has not been widely investigated. The reported rate of pre-treatment LTFU is however lower in studies where Xpert MTB/Rif (Xpert) has been used onsite as opposed to centrally. The use of the Xpert at point of care (POC) could have a role in reducing the pre-treatment LTFU rate among TB patients. We aimed to determine the pre-treatment LTFU rate and the time to treatment initiation as well as to describe associated factors in patients diagnosed with TB using POC Xpert or smear microscopy. METHOD: Xpert machines were installed at 7 primary healthcare facilities in inner-city Johannesburg. POC Xpert TB testing was the primary diagnostic method for all patients although there were some patients who were tested using only laboratory-based smear microscopy (during power outages or machine operator off-sick). Data on patients' demographics, TB diagnostic test (Xpert or smear microscopy), test result, and time to treatment initiation were collected. Associations and predictors of pre-treatment LTFU and time to treatment initiation were explored. FINDINGS: A total of 1981 people with presumptive TB were tested (1743 using Xpert and 238 using smear). A bacteriological diagnosis of TB was made in 271 patients (90% Xpert; 10% smear). The median time to treatment initiation in the smear group was 9 days (IQR: 4-20) while those tested using Xpert had a median time of 0 days (IQR: 0-0). Pre-treatment LTFU was 22.5% with no difference between diagnostic groups (p = 0.8). CONCLUSION: The Pre-treatment LTFU rate of 22.5% found in this study is much higher than the 5% target of the South African National TB Control Program. POC Xpert resulted in a significantly greater proportion of bacteriologically proven TB patients being started on treatment within 30 days of presentation. No risk factors associated with pre-treatment LTFU were identified.

Community health worker perspectives on a new primary health care initiative in the Eastern Cape of South Africa.

BACKGROUND: In 2010, South Africa's National Department of Health launched a national primary health care (PHC) initiative to strengthen health promotion, disease prevention, and early disease detection. The strategy, called Re-engineering Primary Health Care (rPHC), aims to provide a preventive and health-promoting community-based PHC model. A key component of rPHC is the use of community-based outreach teams staffed by generalist community health workers (CHWs). METHODS: We conducted focus group discussions and surveys on the knowledge and attitudes of 91 CHWs working on community-based rPHC teams in the King Sabata Dalindyebo (KSD) sub-district of Eastern Cape Province. RESULTS: The CHWs we studied enjoyed their work and found it meaningful, as they saw themselves as agents of change. They also perceived weaknesses in the implementation of outreach team oversight, and desired field-based training and more supervision in the community. CONCLUSIONS: There is a need to provide CHWs with basic resources like equipment, supplies and transport to improve their acceptability and credibility to the communities they serve.

Tuberculosis case finding: evaluation of a paper slip method to trace contacts.

SETTING: South Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB. OBJECTIVE: To evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing. METHOD: TB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability. RESULTS: From 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV. CONCLUSION: This simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.

Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis.

BACKGROUND: We aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than that of the tuberculin skin test (TST). METHODS: Longitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals. FINDINGS: 15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42-3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 [95% CI 1·29-3·46] for IGRA vs 1·60 [0·94-2·72] for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals. INTERPRETATION: Neither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone. FUNDING: Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.

Evaluation of a service provider short course for prevention of fetal alcohol syndrome.

OBJECTIVE: South Africa has among the highest reported rates of Fetal Alcohol Syndrome (FAS) globally. Primary prevention targeting women at risk for alcohol-exposed pregnancies could substantially reduce the incidence of FAS. We evaluated the effectiveness of a short training intervention to improve service providers' screening, identification, and management of women at risk for alcohol-exposed pregnancies. METHOD: Training to screen and counsel women at risk for alcohol-exposed pregnancies was offered to 86 service providers (95% of whom were female) in two municipalities in the Western Cape Province, South Africa. Effectiveness was evaluated through a before-after study of service providers' knowledge and confidence levels and a comparison of service providers' practices (assessed indirectly via service user exit interviews) at intervention and control clinics. RESULTS: The proportion of service providers indicating that alcohol use during pregnancy is harmful to the fetus increased after training (23% vs. 67%; p < .001). After training, providers expressed significantly more confidence for four skills indicators related to the identification and management of women at risk for an alcohol-exposed pregnancy. Female clients at intervention clinics were more likely than those at the control clinics to receive alcohol advice (odds ratio [OR] = 2.13, 95% CI [1.27, 3.53]), counseling (OR = 1.3, 95% CI [1.05, 1.56]), and an offer of family planning (OR = 1.1, 95% CI [1.06, 2.10]) after the training. Time × Group interaction variable analysis in multiple logistic regression modeling confirmed these effects as related to training. CONCLUSIONS: A short training course based on brief motivational interviewing principles appears to be effective in building service provider capacity to better prevent and manage women at risk for alcohol-exposed pregnancies.

Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth.

BACKGROUND: In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. However, although >1 million deaths due to preterm birth occur annually, antenatal steroids are not routine practice in low-income countries where most of these deaths occur. OBJECTIVES: To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries. METHODS: We conducted systematic reviews using standardized abstraction forms. Quality of evidence was assessed using an adapted GRADE approach. Existing meta-analyses were reviewed for relevance to low/middle-income countries, and new meta-analysis was performed. RESULTS: We identified 44 studies, including 18 randomised control trials (RCTs) (14 in high-income countries) in a Cochrane meta-analysis, which suggested that antenatal steroids decrease neonatal mortality among preterm infants (<36 weeks gestation) by 31% [relative risk (RR) = 0.69; 95% confidence interval (CI) 0.58-0.81]. Our new meta-analysis of four RCTs from middle-income countries suggests 53% mortality reduction (RR = 0.47; 95% CI 0.35-0.64) and 37% morbidity reduction (RR = 0.63; 95% CI 0.49-0.81). Observational study mortality data were consistent. The control group in these equivalent studies was routine care (ventilation and, in many cases, surfactant). In low-income countries, many preterm babies currently receive little or no medical care. It is plausible that antenatal steroids may be of even greater effect when tested in these settings. CONCLUSIONS: Based on high-grade evidence, antenatal steroid therapy is very effective in preventing neonatal mortality and morbidity, yet remains at low coverage in low/middle-income countries. If fully scaled up, this intervention could save up to 500 000 neonatal lives annually.

'Kangaroo mother care' to prevent neonatal deaths due to preterm birth complications.

BACKGROUND: 'Kangaroo mother care' (KMC) includes thermal care through continuous skin-to-skin contact, support for exclusive breastfeeding or other appropriate feeding, and early recognition/response to illness. Whilst increasingly accepted in both high- and low-income countries, a Cochrane review (2003) did not find evidence of KMC's mortality benefit, and did not report neonatal-specific data. OBJECTIVES: The objectives of this study were to review the evidence, and estimate the effect of KMC on neonatal mortality due to complications of preterm birth. METHODS: We conducted systematic reviews. Standardized abstraction tables were used and study quality assessed by adapted GRADE methodology. Meta-analyses were undertaken. RESULTS: We identified 15 studies reporting mortality and/or morbidity outcomes including nine randomized controlled trials (RCTs) and six observational studies all from low- or middle-income settings. Except one, all were hospital-based and included only babies of birth-weight <2000 g (assumed preterm). The one community-based trial had missing birthweight data, as well as other limitations and was excluded. Neonatal-specific data were supplied by two authors. Meta-analysis of three RCTs commencing KMC in the first week of life showed a significant reduction in neonatal mortality [relative risk (RR) 0.49, 95% confidence interval (CI) 0.29-0.82] compared with standard care. A meta-analysis of three observational studies also suggested significant mortality benefit (RR 0.68, 95% CI 0.58-0.79). Five RCTs suggested significant reductions in serious morbidity for babies <2000 g (RR 0.34, 95% CI 0.17-0.65). CONCLUSION: This is the first published meta-analysis showing that KMC substantially reduces neonatal mortality amongst preterm babies (birth weight <2000 g) in hospital, and is highly effective in reducing severe morbidity, particularly from infection. However, KMC remains unavailable at-scale in most low-income countries.