Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa.

BACKGROUND: There is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide TB incidence and mortality. METHODS: We developed an individual-based model of Mtb transmission in households, primary healthcare (PHC) clinics, and all other congregate settings. The model was parameterised using data from a high HIV prevalence community in South Africa, including data on social contact by setting, by sex, age, and HIV/antiretroviral therapy status; and data on TB prevalence in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics, and the impact of a range of IPC interventions in clinics on community-wide TB. RESULTS: We estimate that 7.6% (plausible range 3.9%-13.9%) of non-multidrug resistant and multidrug resistant TB in adults resulted directly from transmission in PHC clinics in the community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%-16.8%), compared with 5.3% (2.7%-10.1%) in HIV-negative people. We estimate that IPC interventions could reduce incident TB cases in the community in 2021-2030 by 3.4%-8.0%, and deaths by 3.0%-7.2%. CONCLUSIONS: A non-trivial proportion of TB results from transmission in clinics in the study community, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We recommend that IPC measures in clinics should be implemented for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community

Prevalence of sexually transmitted infections among young people in South Africa: A nested survey in a health and demographic surveillance site.

BACKGROUND: Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15-24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa. METHODS AND FINDINGS: A total of 1,342 young people, stratified by age (15-19 and 20-24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home. CONCLUSIONS: A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes

Direct estimates of absolute ventilation and estimated Mycobacterium tuberculosis transmission risk in clinics in South Africa

From PLOS via Jisc Publications RouterHistory: collection 2022, received 2022-01-26, accepted 2022-10-03, epub 2022-11-02Acknowledgements: We are grateful to the clinical and management staff at 10 clinics where we obtained ventilation measurements. We thank Thomas Murray, Harriet Gliddon, and Sinethemba Mabuyakhulu who assisted us with ventilation measurements in KZN. We are grateful to Rod Escombe, Ed Nardell, Jon Taylor, Don Milton, and Toby van Reenen for useful discussions about various aspects of ventilation science–they take no responsibility for the content of this manuscript.Publication status: PublishedFunder: Economic and Social Research Council; funder-id: http://dx.doi.org/10.13039/501100000269; Grant(s): ES/P008011/1Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 218261/Z/19/ZFunder: National Institute for Health Research; funder-id: http://dx.doi.org/10.13039/501100000272Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis. Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk. We measured ventilation in clinic spaces using a tracer-gas release method. In spaces where this was not possible, we estimated ventilation using data on indoor and outdoor carbon dioxide levels. Ventilation was measured i) under usual conditions and ii) with all windows and doors fully open. Under various assumptions about infectiousness and duration of exposure, measured absolute ventilation rates were related to risk of Mycobacterium tuberculosis transmission using the Wells-Riley Equation. In 2019, we obtained ventilation measurements in 33 clinical spaces in 10 clinics: 13 consultation rooms, 16 waiting areas and 4 other clinical spaces. Under usual conditions, the absolute ventilation rate was much higher in waiting rooms (median 1769 m3/hr, range 338–4815 m3/hr) than in consultation rooms (median 197 m3/hr, range 0–1451 m3/hr). When compared with usual conditions, fully opening existing doors and windows resulted in a median two-fold increase in ventilation. Using standard assumptions about infectiousness, we estimated that a health worker would have a 24.8% annual risk of becoming infected with Mycobacterium tuberculosis, and that a patient would have an 0.1% risk of becoming infected per visit. Opening existing doors and windows and rearranging patient pathways to preferentially use better ventilated clinic spaces result in important reductions in Mycobacterium tuberculosis transmission risk. However, unless combined with other tuberculosis infection prevention and control interventions, these changes are insufficient to reduce risk to health workers, and other highly exposed individuals, to acceptable levels

Waiting times, patient flow, and occupancy density in South African primary health care clinics: implications for infection prevention and control

AbstractBackgroundTransmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. In clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa, we estimated clinic visit duration, time spent indoors and outdoors, and occupancy density of waiting rooms.MethodsWe used unique barcodes to track attendees’ movements in 11 clinics in two provinces, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration.Results2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p&lt;0.001) and attending with a baby (18.8 minutes longer than those without; p&lt;0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p&lt;0.001) and attendance for tuberculosis or ante/postnatal care (24.8 and 32.6 minutes shorter, respectively, than HIV/acute care; p&lt;0.01).Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1– 75]) of their time outdoors.In two clinics in KZN (no appointment system), occupancy densities of ∼2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance.ConclusionsLonger waiting times were associated with early arrival, being female, and attending with a young child. Attendees generally waited where they were asked to. Regular estimation of occupancy density (as patient flow proxy) may help staff assess for risk of infection transmission and guide intervention to reduce time spent in risky spaces.</jats:sec

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics

From PLOS via Jisc Publications RouterHistory: received 2021-09-01, collection 2022, accepted 2022-06-13, epub 2022-07-20Publication status: PublishedFunder: Economic and Social Research Council; funder-id: http://dx.doi.org/10.13039/501100000269; Grant(s): ES/P008011/1Funder: The Bloomsbury SET; Grant(s): CCF17-7779Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and ‘patient flow’ would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees’ movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1–75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow

Estimating ventilation rates in rooms with varying occupancy levels: Relevance for reducing transmission risk of airborne pathogens

From PLOS via Jisc Publications RouterBackground: In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed. Methods: The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model. Results: The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632–3181] and Q from approach 2 was 2743 l/s [95% CI: 2139–4429]. Conclusions: We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.Funding: The support of the Economic and Social Research Council (ESRC) is gratefully acknowledged. The project is partly funded by the Antimicrobial Resistance Cross Council Initiative supported by the seven research councils in partnership with other funders including support from the GCRF, Grant reference: ES/P008011/1. ASK is funded by The Bloomsbury SET (Research England), grant ref CCF17-7779, AWCY is funded by a Wellcome Trust Investigator Award to Becca Asquith (103865Z/14/Z), AD, NM and RGW are funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement that is also part of the EDCTP2 programme supported by the European Union MR/P002404/1. RGW is additionally supported by the Bill and Melinda Gates Foundation (TB Modelling and Analysis Consortium: OPP1084276/OPP1135288, CORTIS: OPP1137034/OPP1151915, Vaccines: OPP1160830), UNITAID (4214-LSHTM-Sept15; PO 8477-0-600), and ESRC (ES/P008011/1). TAY is funded by an NIHR Academic Clinical Fellowship (ACF-2018-21-007) and acknowledges support from the NIHR Imperial Biomedical Research Centre (BRC). ADG is supported by ESRC (ES/P008011/1), the Bill and Melinda Gates Foundation (OPP1212544_2019) and the US National Institutes of Allergy and Infectious Diseases (1R01A1147321-01). NM and DS are supported by the Wellcome Trust grant number 218261/Z/19/Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.16pubpub

Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa

From BMJ via Jisc Publications RouterHistory: received 2021-08-07, accepted 2022-03-20, ppub 2022-04, epub 2022-04-08Publication status: PublishedAaron S. Karat - ORCID: 0000-0001-9643-664X http://orcid.org/0000-0001-9643-664XKarin Diaconu - ORCID: 0000-0002-5810-9725 http://orcid.org/0000-0002-5810-9725Karina Kielmann - ORCID: 0000-0001-5519-1658 http://orcid.org/0000-0001-5519-1658Background: There is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide TB incidence and mortality. Methods: We developed an individual-based model of Mtb transmission in households, primary healthcare (PHC) clinics, and all other congregate settings. The model was parameterised using data from a high HIV prevalence community in South Africa, including data on social contact by setting, by sex, age, and HIV/antiretroviral therapy status; and data on TB prevalence in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics, and the impact of a range of IPC interventions in clinics on community-wide TB. Results: We estimate that 7.6% (plausible range 3.9%–13.9%) of non-multidrug resistant and multidrug resistant TB in adults resulted directly from transmission in PHC clinics in the community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%–16.8%), compared with 5.3% (2.7%–10.1%) in HIV-negative people. We estimate that IPC interventions could reduce incident TB cases in the community in 2021–2030 by 3.4%–8.0%, and deaths by 3.0%–7.2%. Conclusions: A non-trivial proportion of TB results from transmission in clinics in the study community, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We recommend that IPC measures in clinics should be implemented for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community.The support of the Economic and Social Research Council (UK) is gratefully acknowledged. The project is partly funded by the Antimicrobial Resistance Cross Council Initiative supported by the seven research councils in partnership with other funders including support from the GCRF. Grant reference: ES/P008011/1. NM is additionally funded the Wellcome Trust (218261/Z/19/Z). RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 & INV-001754), and the WHO (2020/985800-0). RMGJH is funded by ERC (action number 757699). TAY receives an NIHR Academic Clinical Fellowship.7pubpub

A dose-reduction HPV vaccine immunobridging trial of two HPV vaccines among adolescent girls in Tanzania (the DoRIS trial) - Study protocol for a randomised controlled trial.

BACKGROUND: Human papillomavirus (HPV) infection is the primary cause of cervical cancer. In 2018, the World Health Organization (WHO) Director General announced his commitment to eliminate cervical cancer, with HPV vaccination as a priority. However, the costs of setting up a multi-dose HPV vaccination programme remain a barrier to its introduction. METHODS/DESIGN: We are conducting a randomised-controlled trial of reduced dose schedules of HPV vaccine in Tanzania to establish whether a single dose produces immune responses that will be effective in preventing cervical cancer. 930 girls aged 9-14 years in Mwanza, Tanzania, were randomised to one of 6 arms, comprising 3 different dose schedules of the 2-valent (Cervarix) and 9-valent (Gardasil-9) HPV vaccines: 3 doses; 2 doses given 6 months apart; or a single dose. All participants will be followed for 36 months; those in the 1 and 2 dose arms will be followed for 60 months. Trial outcomes focus on vaccine immune responses including HPV 16/18-specific antibody levels, antibody avidity, and memory B cell responses. Results will be immunobridged to historical cohorts of girls and young women in whom efficacy has been demonstrated. DISCUSSION: This is the first randomised trial of the single dose HPV vaccine schedule in the target age group. The trial will allow us to examine the quality and durability of immune responses of reduced dose schedules in a population with high burden of malaria and other infections that may affect vaccine immune responses. Initial results (24 months) are expected to be published in early 2021

Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa

Aaron S Karat - ORCID: 0000-0001-9643-664X https://orcid.org/0000-0001-9643-664XKarin Diaconu - ORCID: 0000-0002-5810-9725 https://orcid.org/0000-0002-5810-9725Karina Kielmann - ORCID: 0000-0001-5519-1658 https://orcid.org/0000-0001-5519-1658Background Elevated rates of tuberculosis in health care workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.Methods An individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions – co-developed with health professionals and policymakers - were simulated: 1. queue management systems with outdoor waiting areas, 2. ultraviolet germicidal irradiation systems (UVGI), 3. appointment systems, 4. opening windows and doors, 5. surgical mask wearing by clinic attendees, 6. simple clinic retrofits, and 7. increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the CCMDD service.Results In the model, 1. outdoor waiting areas reduced the transmission to clinic attendees by 83% (interquartile range [IQR] 76-88%), 2. UVGI by 77% (IQR 64-85%), 3. appointment systems by 62% (IQR 45-75%), 4. opening windows and doors by 55% (IQR 25-72%), 5. masks by 47% (IQR 42-50%), 6. clinic retrofits by 45% (IQR 16-64%), and 7. increasing the coverage of CCMDD by 22% (IQR 12-32%).Conclusions The majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.The support of the Economic and Social Research Council (IK) is gratefully acknowledged. The project is partly funded by the Antimicrobial Resistance Cross Council Initiative supported by the seven research councils in partnership with other funders including support from the GCRF. Grant reference: ES/P008011/1. NM is additionally funded the Wellcome Trust (218261/Z/19/Z). RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 & INV-001754), and the WHO (2020/985800-0). TAY is funded via an NIHR Academic Clinical Fellowship. RMGHJ is funded by ERC (action number 757699)https://doi.org/10.1136/bmjgh-2021-0071246pubpub1

Correlates of HIV-1 Genital Shedding in Tanzanian Women

BACKGROUND: Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo) in Tanzania. METHODOLOGY: Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs) at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load. PRINCIPAL FINDINGS: Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load. CONCLUSIONS: RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services