Perceived stigma among people with TB and household contacts.

BACKGROUND: TB-related stigma hampers access to diagnosis and treatment, making it important to understand the demographic and clinical characteristics associated with perceived TB stigma. TB stigma has not been studied in household contacts before, yet they comprise an important population for epidemic control, with high risk of infection.METHOD: A cross-sectional study was conducted among people with TB and household contacts in South Africa using a 12-item perceived TB stigma scale (score range: 0-36). Demographic and clinical characteristic data were collected using a close-ended questionnaire. A linear mixed-effects regression model was used to explore perceived TB stigma levels and its associated characteristics.RESULTS: The sample included 143 people with TB and 135 household contacts. The mean perceived TB stigma score among people with TB was 22.1 (95% CI 21.1-23.1) and 22.2 (95% CI 21.1-23.3) among household contacts. Being in the same household explained 24.3% variability in stigma perception. Residence in the urban study site (Soshanguve) and a positive HIV diagnosis were associated with higher perceived TB stigma score.CONCLUSIONS: People with TB and household contacts have similarly high prevalence of perceived TB stigma. Positive HIV status and urban location were associated with higher prevalence of perceived TB stigma.

Time to care-seeking for TB symptoms.

BACKGROUND: Early presentation to healthcare facilities is critical for early diagnosis and treatment of TB. We studied self-reported time to care-seeking from the onset of TB symptoms among primary healthcare clinic (PHC) attendees in Limpopo Province, South Africa.METHODS: We used data from participants enrolled in a cluster-randomized trial of TB case finding in 56 PHC clinics across two health districts. We fitted log-normal accelerated failure time regression models and we present time ratios (TRs) for potential risk factors.RESULTS: We included 2,160 participants. Among the 1,757 (81%) diagnosed with active TB, the median time to care-seeking was 30 days (IQR 14-60); adults sought care later than children/adolescents (adjusted TR aTR 1.47, 95% CI 1.10-1.96). Among those not diagnosed with TB, the median was 14 days (IQR 7-60); being HIV-positive (aTR 1.57, 95% CI 1.03-2.40); having less than grade 8 education and currently smoking were associated with longer time to care-seeking. In the combined analysis, living with HIV and having underlying active TB was associated with faster care-seeking (TB status x HIV interaction: TR 0.68, 95% CI 0.48-0.96).CONCLUSION: Delay in care-seeking was associated with age, lower education and being a current smoker. TB awareness campaigns targeting these population groups may improve care-seeking behavior and reduce community TB transmission.

The impact of a mobile COVID-19 polymerase chain reaction laboratory at a large tertiary hospital during the first wave of the pandemic: A retrospective analysis.

BACKGROUND: The onset of the COVID-19 pandemic in South Africa (SA) created numerous supply challenges. Demand for diagnostic testing overwhelmed the capacity to deliver. We describe the utility and outcomes of a mobile laboratory staffed by non-laboratory healthcare workers and established to perform polymerase chain reaction (PCR) testing for the rapid diagnosis of COVID-19 at a large hospital in SA. OBJECTIVES: To describe the performance of the mobile PCR COVID-19 laboratory. The secondary objective was to determine the prevalence of COVID-19 infections in the non-COVID intensive care unit (ICU). METHODS: This was a retrospective descriptive study of data from the newly established mobile COVID-19 PCR laboratory database and the non-COVID ICU database during the first peak of the COVID-19 pandemic (20 May - 8 August 2020) at a tertiary hospital in SA. RESULTS: The mobile laboratory received 1 113 emergency COVID-19 PCR test requests for patients with non-COVID clinical presentations. The median (interquartile range) turnaround time was 152 (123 - 184) minutes (n=36). Primary outcome (20 May - 19 June, n=315): The sensitivity and specificity were 95% and 97%, respectively, and the positive and negative predictive values 82.4% and 99.2%, respectively. Secondary outcomes (9 June - 8 August): The prevalence of COVID-19 infections among patients admitted to the multidisciplinary adult and paediatric non-COVID ICU was 2.4% (n=4/168). The mean (standard deviation) COVID-19 positive rate for the mobile laboratory during this period was 18.1% (6%). The prevalence of COVID-19 infections among medical staff in the non-COVID ICU was 3.1% (n=1/32). CONCLUSIONS: The establishment of a mobile PCR laboratory staffed by non-laboratory healthcare workers during the COVID-19 pandemic provided a rapid, accurate and clinically effective solution for emergency hospital admissions with non-COVID-19 presentations.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Geographic mobility and time to seeking care among people with TB in Limpopo, South Africa.

SETTING: Human mobility contributes to the spread of infectious diseases. South Africa has a long history of internal labor migration and a high burden of TB.METHODS: People newly diagnosed with TB in the Vhembe and Waterberg Districts of Limpopo answered a questionnaire regarding geographic movement over the past year. Participants were classified as 'highly mobile' (spending more than 30 nights at a residence other than their primary residence in the past year, or being ≥250 km from their primary residence at the time of the interview) or 'less mobile'. We explored associations between sociodemographic characteristics and high mobility, and between mobility and time to presentation at a clinic.RESULTS: Of the 717 participants included, 185 (25.7%) were classified as 'highly mobile'. Factors associated with high mobility included living with someone outside of Limpopo Province, HIV-positive status (men only), and current smoking (men only). Highly mobile individuals had similar care-seeking behavior as less mobile individuals (adjusted time ratio 0.9, 95% CI 0.6-1.2, P = 0.304)CONCLUSION: Highly mobile people with TB in Limpopo Province were more likely to live with people from outside the province, smoke, and have HIV. These patients had similar delays in seeking care as less mobile individuals.

Venous thromboembolic disease in adults admitted to hospital in a setting with a high burden of HIV and TB.

BACKGROUND: HIV and tuberculosis (TB) independently cause an increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE are scarce. The Wells' DVT and PE scores are widely used but their utility in these settings has not been reported on extensively. OBJECTIVES: To evaluate new onset VTE, compare clinical characteristics by HIV status, and the presence or absence of TB disease in our setting. We also calculate the Wells' score for all patients. METHODS: A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited into the study between September 2015 and May 2016. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells' score were collected. RESULTS: We recruited 100 patients. Most of the patients were HIV-infected (n=59), 39 had TB disease and 32 were HIV/TB co-infected. Most of the patients had DVT only (n=83); 11 had PE, and 6 had both DVT and PE. More than a third of patients on antiretroviral treatment (ART) (43%; n=18/42) were on treatment for <6 months. Half of the patients (51%; n=20/39) were on TB treatment for <1 month. The median (interquartile range (IQR)) DVT and PE Wells' score in all sub-groups was 3.0 (1.0 - 4.0) and 3.0 (2.5 - 4.5), respectively. CONCLUSION: HIV/TB co-infection appears to confer a risk for VTE, especially early after initiation of ART and/or TB treatment, and therefore requires careful monitoring for VTE and early initiation of thrombo-prophylaxis.

Challenges in recruiting children to a multidrug-resistant TB prevention trial.

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa.METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions.RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment.CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies.

Choice architecture-based prescribing tool for TB preventive therapy: a pilot study in South Africa.

BACKGROUND: All people with HIV who screen negative for active tuberculosis (TB) should receive isoniazid preventive therapy (IPT). IPT implementation remains substantially below the 90% WHO target. This study sought to further understanding of IPT prescription by piloting a simplified prescribing approach. SETTING: Primary care clinics in Matlosana, South Africa. DESIGN: This was a mixed-methods implementation study. METHODS: Nine providers were recruited and underwent training on 2018 WHO guidelines. A simplified prescribing tool containing antiretroviral therapy (ART) and IPT prescriptions was introduced into the workflow for 2 weeks. Prescription data were collected from file review. Interviews were conducted with prescribers. RESULTS: During the study period, 41 patients were evaluated for ART initiation; 34 (83%) files used the simplified prescribing tool. Thirty-seven (90%) patients were eligible for same-day ART and IPT initiation, of whom 36 (97%) received IPT prescription. Qualitative interviews identified the following barriers to IPT prescription: cognitive burden, extensive documentation, limited management support, paucity of training, stock-outs, and patient-related factors. Provider acceptability of the tool was favorable, with unanimous recommendation to colleagues on the basis of streamlining documentation and reminding to prescribe. CONCLUSIONS: This simplified prescribing device for IPT was feasible to implement. Streamlining documentation and reminding providers to prescribe can reduce work-flow barriers to IPT provision.

Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial.

BACKGROUND: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation. METHODS: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue. DISCUSSION: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Subclinical tuberculosis and adverse infant outcomes in pregnant women with HIV.

BACKGROUND: Tuberculosis (TB) in pregnant women with HIV is associated with adverse maternal and infant outcomes. Previous studies have described a substantial prevalence of subclinical TB in this group, but little is known about the impact of subclinical TB on maternal and pediatric outcomes.METHODS: The Tshepiso Study recruited 235 HIV-infected pregnant women with TB (and matched HIV-positive, TB-negative pregnant controls), in Soweto, South Africa, from 2011 to 2014. During enrolment screening, some women initially recruited as controls were subsequently diagnosed with prevalent TB. We therefore assessed the prevalence of subclinical TB, associated participant characteristics and outcomes.RESULTS: Of 162 women initially recruited as TB-negative controls, seven (4.3%) were found to have TB on sputum culture. All seven had negative WHO symptom screens, and six (86%) were smear-negative. Of their seven infants, one was diagnosed with TB, and three (43%) experienced complications compared to zero infants with TB and 11% experiencing complications in the control group of TB-negative mothers (P = 0.045).CONCLUSION: We discovered an appreciable prevalence of subclinical TB in HIV-infected pregnant women in Soweto, which had not been detected by screening algorithms based solely on symptoms. Infants of HIV-infected mothers with subclinical TB appear to have a higher risk of adverse outcomes than those of TB-negative mothers.

Priorities among HIV-positive individuals for tuberculosis preventive therapies.

BACKGROUND: There has been slow uptake of isoniazid preventive therapy (IPT) among people living with HIV (PLWH).METHODS: We surveyed adults recently diagnosed with HIV in 14 South African primary health clinics. Based on the literature and qualitative interviews, sixteen potential barriers and facilitators related to preventive therapy among PLWH were selected. Best-worst scaling (BWS) was used to quantify the relative importance of the attributes. BWS scores were calculated based on the frequency of participants' selecting each attribute as the best or worst among six options (across multiple choice sets) and rescaled from 0 (always selected as worst) to 100 (always selected as best) and compared by currently receiving IPT or not.RESULTS: Among 342 patients surveyed, 33% (n = 114) were currently taking IPT. Having the same standard of life as someone without HIV was most highly prioritized (BWS score = 67.3, SE = 0.6), followed by trust in healthcare providers (score, 66.3 ± 0.6). Poor standard of care in public clinics (score, 30.6 ± 0.6) and side effects of medications (score, 33.7 ± 0.6) were least prioritized. BWS scores differed by IPT status for few attributes, but overall ranking was similar (spearman's rho = 0.9).CONCLUSION: Perceived benefits of preventive therapy were high among PLWH. IPT prescription by healthcare providers should be encouraged to enhance IPT uptake among PLWH.

Tuberculosis patients with higher levels of poverty face equal or greater costs of illness.

SETTING: Fifty-six public clinics in Limpopo Province, South Africa.OBJECTIVE: To evaluate the association between tuberculosis (TB) patient costs and poverty as measured by a multidimensional poverty index.DESIGN: We performed cross-sectional interviews of consecutive patients with TB. TB episode costs were estimated from self-reported income, travel costs, and care-seeking time. Poverty was assessed using the South African Multidimensional Poverty Index (SAMPI) deprivation score (a 12-item household-level index), with higher scores indicating greater poverty. We used multivariable linear regression to adjust for age, sex, human immunodeficiency virus status and travel time.RESULTS: Among 323 participants, 108 (33%) were 'deprived' (deprivation score >0.33). For each 0.1-unit increase in deprivation score, absolute TB episode costs were 1.11 times greater (95%CI 0.97-1.26). TB episode costs were 1.19 times greater with each quintile of higher deprivation score (95%CI 1.00-1.40), but lower by a factor of 0.54 with each quintile of lower self-reported income (higher poverty, 95%CI 0.46-0.62).CONCLUSION: Individuals experiencing multidimensional poverty and the cost of tuberculosis illness in Limpopo, South Africa faced equal or higher costs of TB than non-impoverished patients. Individuals with lower self-reported income experienced higher costs as a proportion of household income but lower absolute costs. Targeted interventions are needed to reduce the economic burden of TB on patients with multidimensional poverty.

Detection and molecular characterization of urinary tract HIV-1 populations.

BACKGROUND: Identification of all possible HIV reservoirs is an important aspect in HIV eradication efforts. The urinary tract has however not been well studied as a potential HIV reservoir. In this pilot study we molecularly characterized HIV-1 viruses in urine and plasma samples to investigate HIV-1 replication, compartmentalization and persistence in the urinary tract. METHODS: Prospectively collected urine and blood samples collected over 12-36 months from 20 HIV-1 infected individuals were analysed including sampling points from prior to and after ART initiation. HIV-1 pol gene RNA and DNA from urine supernatant and urine pellets respectively were analysed and compared to plasma RNA viruses from the same individual. RESULTS: HIV-1 nucleic acid was detected in urine samples from at least one time point in 8/20 (40%) treatment-naïve subjects compared to 1/13 (7.7%) individuals on antiretroviral treatment (ART) during periods of plasma viral suppression and 1/7 (14.3%) individuals with virological failure. HIV-1 RNA was undetectable in urine samples after ART initiation but HIV-1 DNA was detectable in one patient more than 6 months after treatment initiation. There was co-clustering of urine-derived pol sequences but some urine-derived sequences were interspersed among the plasma-derived sequences. CONCLUSIONS: Suppressive ART reduces HIV-1 replication in the urinary tract but HIV-1 DNA may persist in these cells despite treatment. A larger number of sequences would be required to confirm HIV compartmentalization in the urinary tract.

An observational study of safe and risky practices in funeral homes in South Africa.

BACKGROUND: Funeral home personnel are at risk of exposure to infectious hazards. The high prevalence of infectious diseases in South Africa means that these workers and family members of deceased individuals are vulnerable to infection if proper safety measures and equipment are not used. OBJECTIVES:  To collect observational information on funeral industry practices in order to assess the safety of handling corpses and exposure to risk that could result in disease transmission. METHODS: A cross-sectional study was conducted across two locations from August to October 2015. Funeral homes in Klerksdorp and Soweto were approached. The study team did facility assessments and observed preparation practices, focusing on safety equipment, personal protective equipment (PPE) and contact with hazardous materials. Interviews with funeral home personnel and relatives of the deceased were also conducted. RESULTS: Of the funeral homes, 23.0% (20/87) agreed to participate. A median of 5 personnel (interquartile range 4 - 8) were employed per facility. It was observed that not all PPE was used despite availability. Gloves, aprons and face masks were most commonly worn, and no personnel were observed wearing boots, gowns or plastic sleeves. Funeral homes were located near food outlets, schools and open public spaces, and not all had access to proper biohazardous waste disposal services. Of 5 family members who were interviewed for the study, none reported being willing to partake in the funeral preparation procedure. CONCLUSIONS: There is a need to standardise the use of safety equipment, waste disposal methods and location designation in the funeral industry.

Mobile phone access and comfort: implications for HIV and tuberculosis care in India and South Africa.

SETTING: India and South Africa shoulder the greatest burden of tuberculosis (TB) and human immunodeficiency virus (HIV) infection respectively, but care retention is suboptimal.OBJECTIVE: We conducted a study in Pune, India, and Matlosana, South Africa, 1) to identify the factors associated with mobile phone access and comfort of use, 2) to assess access patterns.DESIGN: A cross-sectional study assessed mobile phone access, and comfort; a longitudinal study assessed access patterns.RESULTS: We enrolled 261 participants: 136 in India and 125 in South Africa. Between 1 week and 6 months, participant contact decreased from 90% (n = 122) to 57% (n = 75) in India and from 93% (n = 116) to 70% (n = 88) in South Africa. In the latter, a reason for a clinic visit for HIV management was associated with 63% lower odds of contact than other priorities (e.g., diabetes mellitus, maternal health, TB). In India, 57% (n = 78) reported discomfort with texting; discomfort was higher in the unemployed (adjusted OR [aOR] 4.97, 95%CI 1.12-22.09) and those aged ≥35 years (aOR 1.10, 95%CI 1.04-1.16) participants, but lower in those with higher education (aOR 0.04, 95% CI 0.01-1.14). In South Africa, 91% (n = 114) reported comfort with texting.CONCLUSION: Mobile phone contact was poor at 6 months. While mHealth could transform TB-HIV care, alternative approaches may be needed for certain subpopulations.

Risk factors for catastrophic costs associated with tuberculosis in rural South Africa.

Fifty-five public clinics in northern South Africa. To estimate patient costs and identify the factors associated with catastrophic costs among individuals treated for tuberculosis (TB). We performed cross-sectional interviews of consecutive patients at public clinics from October 2017 to January 2018. 'Catastrophic costs' were defined as costs totalling ≥20% of annual household income. For participants with no reported income, we considered scenarios where costs were considered non-catastrophic if 1) costs totalled Among 327 participants, the estimated mean TB episode costs were US$365 (95%CI 233-498): out-of-pocket costs comprised 58% of costs, wages lost due to health care-seeking represented 26%, and income reduction accounted for 16% of costs. Ninety (28%) participants experienced catastrophic costs, which were associated with clinic travel times of 60-90 min (adjusted prevalence ratio [aPR] 1.7, 95%CI 0.9-3.1), unemployment (aPR 2.0, 95%CI 1.0-4.0) and having fewer household members (aPR 0.6, 95%CI 0.3-1.0). In rural South Africa, catastrophic costs from TB are common and associated with distance to clinics, unemployment, and household size. These findings can help tailor social protection programs and enhance service delivery to patients at greatest risk of experiencing financial hardship. .