Relationship between social adversity in two year olds and C-reactive protein in eighteen year olds in the birth-to twenty cohort

A research report Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Masters of Science in Epidemiology and Biostatistics 15 June 2017, Johannesburg, South AfricaIntroduction: Worldwide, cardiovascular diseases are the number one cause of death with a three-quarter of cardiovascular disease deaths occurring in low-middle income countries. Childhood social adversity as a proxy of psychosocial stress has been found to be associated with later adult risk of cardiovascular diseases, with studies investigating the mechanisms linking early exposure to social adversity and later risk of cardiovascular diseases. CRP has been a biomarker that is found to be associated with the risk of cardiovascular diseases in adults, however, the association between CRP levels in adolescence and social adversity in children (prenatal and postnatal periods) is not well documented. Assessing the association between childhood social adversity and CRP levels in late adolescent period will encourage further studies to explore whether high levels of CRP tracks from adolescence to adulthood and ultimately increase the risk of cardiovascular diseases in the South African context. Aim: This study aims to determine the association between social adversity from the prenatal period to two years of age and the level of CRP in the same cohort at the age of 18 (from 1990 to 2008) Methods: The study was a secondary data analysis of the Birth to Twenty longitudinal study which recruited 3273 singleton children. Four measures (prenatal and postnatal (0-2 years)) of social adversity in children (which are maternal prenatal stress, maternal prenatal general feeling, maternal postnatal depression and household socioeconomic status) were used. The high-sensitivity C-reactive protein was grouped into tertiles (1st tertile: hs-CRP1.16) and multinomial logistic regressions were therefore used to assess the association between childhood social adversities and tertiles of high sensitivity C-reactive protein. Results: The primary Birth to Twenty longitudinal study had more than 35% loss to follow-up at 18 years. No statistically significant difference (p>0.05) was found on demographic variables of those included in the analysis compared to those not included (due to current study criteria and loss to follow-up). A unit increase in maternal marital stress score during pregnancy was associated with an increase by 2.23 (p=0.03) in the relative risk of the youth being in the 2nd high sensitivity C-reactive protein tertile in comparison to being in the 1st high sensitivity C-reactive protein tertile. For a unit increase in maternal family stress score, the relative risk of the youth being in the 3rd high sensitivity C-reactive protein is 1.61 (p=0.04) times greater in comparison to being in the 1st high sensitivity C-reactive protein tertile. No statistically significant associations were observed among the other categories of social adversity (p>0.05) and high sensitivity C-reactive proteins. Low social support to mothers during pregnancy was associated with elevated high-sensitivity C-reactive protein in adolescents. Conclusion: A positive association was observed between a prenatal measure of social adversity and elevated high-sensitivity C-reactive protein; In particular, increased levels of family and relationship-related prenatal stress during pregnancy is a predictor of elevated high-sensitivity C-reactive protein in children. This study contributes to the empirical evidence from studies done in animals suggesting that early development of adult health complication starts during the intrauterine period. The findings of this study will further guide intervention research to target conditions during intrauterine period in preventing adult health complications.MT201

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa

BACKGROUND: Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. METHODS: We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. RESULTS: Among 619 women, 61% (n =380) were from Tshwane District and 39% (n =239) from Cape Town; 79% (n =486) were women living with HIV. The prevalence of any STI was 37% (n =228); C. trachomatis, 26% (n =158), T. vaginalis, 18% (n =120) and N. gonorrhoeae, 6% (n =40). There were 93% (n =574) singleton live births, 5% (n =29) miscarriages and 2% (n =16) stillbirths. Among the live births, there were 1% (n =3) neonatal deaths, 7% (n =35) low birthweight in full-term babies and 10% (n =62) preterm delivery. There were 24% (n =146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV. CONCLUSION: Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases & National Institutes of Health.http://www.biomedcentral.com/bmcpregnancychildbirthMedical Microbiolog

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa

Background Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. Methods We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. Results Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV. Conclusion Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation

Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized-controlled hybrid-effectiveness trial

Background Sexually transmitted infections (STIs) during pregnancy are associated with adverse birth outcomes, including preterm birth, low birth weight, perinatal death, and congenital infections such as increased mother-to-child HIV transmission. Prevalence of STIs among pregnant women in South Africa remains high, with most women being asymptomatic for their infection(s). Unfortunately, most STIs remain undetected and untreated due to standard practice syndromic management in accordance with World Health Organization (WHO) guidelines. Although lab-based and point-of-care molecular tests are available, optimal screening strategies during pregnancy, their health impact, and cost-effectiveness are unknown. Methods We will implement a 3-arm (1:1:1) type-1 hybrid effectiveness-implementation randomized-controlled trial (RCT). We will enroll 2500 pregnant women attending their first antenatal care (ANC) visit for their current pregnancy at participating health facilities in Buffalo City Metro District, Eastern Cape Province, South Africa. Participants allocated to arms 1 and 2 (intervention) will receive GeneXpert® point-of-care diagnostic testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, with same-day treatment for detected infection(s). Arm 1 will additionally receive a test-of-cure 3 weeks post-treatment, while Arm 2 will receive a repeat test at 30–34 weeks’ gestation. Those allocated to Arm 3 will receive syndromic management (standard-of-care). The RE-AIM framework will be used to guide collection of implementation indicators to inform potential future scale up. Primary outcome measures include (1) frequency of adverse birth outcomes among study arms, defined by a composite measure of low birth weight and pre-term delivery, and (2) change in STI prevalence between baseline and birth outcome among intervention arms and compared to standard-of-care. Estimates and comparative costs of the different screening strategies relative to standard-of-care and the costs of managing adverse birth outcomes will be calculated. Cost-effectiveness will be assessed per STI and disability-adjusted life year averted. Discussion This trial is the first RCT designed to identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes. Demonstrating the impact of diagnostic screening and treatment, compared to syndromic management, on birth outcomes will provide critical evidence to inform changes to WHO guidelines for syndromic management of STIs during pregnancy. Trial registration ClinicalTrials.gov NCT04446611 . Registered on 25 June 2020

The Community PrEP Study: a randomized control trial leveraging community-based platforms to improve access and adherence to pre-exposure prophylaxis to prevent HIV among adolescent girls and young women in South Africa—study protocol

Background HIV incidence among South African adolescent girls and young women (AGYW) remains high, but could be reduced by highly effective pre-exposure prophylaxis (PrEP). Unfortunately, AGYW report significant barriers to clinic-based sexual and reproductive health services. Even when AGYW access PrEP as an HIV prevention method, poor prevention-effective use was a serious barrier to achieving its optimal HIV prevention benefits. Determining the acceptability and feasibility of community-based platforms to increase AGYW’s access to PrEP, and evaluating behavioural interventions to improve prevention-effective use of PrEP are needed. Methods We propose a mixed-methods study among AGYW aged 16–25 years in Eastern Cape Province, South Africa. In the first component, a cross-sectional study will assess the acceptability and feasibility of leveraging community-based HIV counselling and testing (CBCT) platforms to refer HIV-negative, at-risk AGYW to non-clinic-based, same-day PrEP initiation services. In the second component, we will enrol 480 AGYW initiating PrEP via our CBCT platforms into a three-armed (1:1:1) randomized control trial (RCT) that will evaluate the effectiveness of adherence support interventions to improve the prevention-effective use of PrEP. Adherence will be measured over 24 months via tenofovir-diphosphate blood concentration levels. Qualitative investigations will explore participant, staff, and community experiences associated with community-based PrEP services, adherence support activities, study implementation, and community awareness. Costs and scalability of service platforms and interventions will be evaluated. Discussion This will be the first study to assess the acceptability and feasibility of leveraging CBCT platforms to identify and refer at-risk AGYW to community-based, same-day PrEP initiation services. It will also provide quantitative and qualitative results to inform adherence support activities and services that promote the prevention-effective use of PrEP among AGYW. By applying principles of implementation science, behavioural science, and health economics research, we aim to inform strategies to improve access to and prevention-effective use of PrEP by AGYW. Trial registration ClinicalTrials.gov NCT03977181 . Registered on 6 June 2019—retrospectively registered

Technology and implementation science to forge the future of evidence-based psychotherapies: the PRIDE scale-up study

Objective: To report the interim results from the training of providers in evidence-based psychotherapies (EBPs) and use of mobile applications. Design and setting: The Partnerships in Research to Implement and Disseminate Sustainable and Scalable Evidence (PRIDE) study is a cluster-randomised hybrid effectiveness-implementation trial comparing three delivery pathways for integrating comprehensive mental healthcare into primary care in Mozambique. Innovations include the use of EBPs and scaling-up of task-shifted mental health services using mobile applications. Main outcome measures: We examined EBP training attendance, certification, knowledge and intentions to deliver each component. We collected qualitative data through rapid ethnography and focus groups. We tracked the use of the mobile applications to investigate early reach of a valid screening tool (Electronic Mental Wellness Tool) and the roll out of the EBPs PARTICIPANTS: Psychiatric technicians and primary care providers trained in the EBPs. Results: PRIDE has trained 110 EBP providers, supervisors and trainers and will train 279 community health workers in upcoming months. The trainings improved knowledge about the EBPs and trainees indicated strong intentions to deliver the EBP core components. Trained providers began using the mobile applications and appear to identify cases and provide appropriate treatment. Conclusions: The future of EBPs requires implementation within existing systems of care with fidelity to their core evidence-based components. To sustainably address the vast mental health treatment gap globally, EBP implementation demands: expanding the mental health workforce by training existing human resources; sequential use of EBPs to comprehensively treat mental disorders and their comorbid presentations and leveraging digital screening and treatment applications. Keywords: adult psychiatry; anxiety disorders; depression & mood disorders; schizophrenia & psychotic disorders; substance misuse. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ

Acceptability and feasibility of leveraging community‐based HIV counselling and testing platforms for same‐day oral PrEP initiation among adolescent girls and young women in Eastern Cape, South Africa

IntroductionCommunity-based delivery of HIV pre-exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home-based services and pop-up tents into existing community-based HIV testing services (CB-HTS) in Eastern Cape Province, South Africa.MethodsAfter accessing CB-HTS via a "pop-up" tent or home-based services, HIV-negative AGYW aged 16-25 years were invited to complete a baseline questionnaire and referred for PrEP services at a community-based PrEP site co-located with pop-up HTS tents. A 30-day supply of PrEP was dispensed. PrEP uptake, time-to-initiation, cohort characteristics and first medication refill within 90 days were measured using descriptive statistics.ResultsOf the 1164 AGYW who tested for HIV, 825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community-based PrEP. Of those, 624 (77.4%) presented for PrEP (482/483 [99.8%] from pop-up HTS and 142/323 [44.0%] from home-based HTS), of which 603 (96.6%) initiated PrEP. Of those initiating PrEP following home-based HTS, 59.1% initiated within 0-3 days, 25.6% within 4-14 days and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop-up HTS initiated PrEP the same day. Among AGWY initiating PrEP, 37.5% had a detectable sexually transmitted infection (STI). Although AGYW reported a low self-perception of HIV risk, post-hoc application of HIV risk assessment measures to available data classified most study participants as high risk for HIV acquisition. Cumulatively, 329 (54.6%) AGYW presented for a first medication refill within 90 days of accepting their first bottle of PrEP.ConclusionsLeveraging CB-HTS platforms to provide same-day PrEP initiation and refill services was acceptable to AGYW. A higher proportion of AGYW initiated PrEP when co-located with CB-HTS sites compared to those referred following home-based HTS, suggesting that proximity of CB-HTS and PrEP services facilitates PrEP uptake among AGYW. The high prevalence of STIs among those initiating PrEP necessitates the integration of STI and HIV prevention programs for AGYW. Eligibility for PrEP initiation should not be required among AHYW in high HIV burden communities. Community-based service delivery will be crucial to maintaining access to PrEP services during the COVID-19 pandemic and future health and humanitarian emergencies

Prevalence, incidence and associated risk factors of STIs during pregnancy in South Africa

OBJECTIVE: STIs during pregnancy increase adverse pregnancy and birth outcomes and may increase HIV risk. STI syndromic management is standard of care in South Africa. Our study evaluated the prevalence and incidence of STIs in pregnant women and the associated risk factors. METHODS: We combined data from two prospective observational studies of pregnant women enrolled while attending their first antenatal clinic (ANC) visit in Tshwane District and Cape Town. Women ≥18 years were tested at first ANC visit and at their first postpartum visit for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis using Xpert assays (Cepheid, USA). We evaluated the prevalence and incidence of STI and the associated risk factors using multivariable regression models. RESULTS: We enrolled 669 pregnant women, 64% (n=427) from Tshwane District and 36% (n=242) from Cape Town; 80% (n=534) were women living with HIV (WLHIV) and 20% (n=135) without HIV. At enrolment, 37% (n=250) were diagnosed with at least one STI, of which 76% (n=190) were asymptomatic. STI prevalence was 40% (n=213) in WLHIV and 27% (n=37) in women without HIV (p=0.01). Baseline STI infection was associated with younger age (OR=0.95 per year, 95% CI 0.92 to 0.98), higher gestational age (adjusted OR (aOR)=1.03 per week, 95% CI 1.00 to 1.05), single relationship status (aOR=1.53, 95% CI 1.09 to 2.15) and HIV status (aOR=1.86, 95% CI 1.17 to 2.95). Of 419 participants with no STI at baseline, 21 had an incident STI during follow-up, with a mean follow-up time of 140 days. The incidence rate of STI during pregnancy and early post partum was 15 infections per 100 women-years (95% CI 9 to 23). Younger age was associated with STI incidence. CONCLUSION: Our study shows high prevalence and incidence of STIs in pregnancy, especially in WLHIV, demonstrating the need for STI screening in ANC to prevent adverse pregnancy and birth outcomes. Most STI cases were asymptomatic and would have gone untreated with syndromic management. Aetiological STI screening is urgently needed to reduce the burden of STIs in pregnancy

Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized‑controlled hybrid‑effectiveness trial

BACKGROUND : Sexually transmitted infections (STIs) during pregnancy are associated with adverse birth outcomes, including preterm birth, low birth weight, perinatal death, and congenital infections such as increased mother-tochild HIV transmission. Prevalence of STIs among pregnant women in South Africa remains high, with most women being asymptomatic for their infection(s). Unfortunately, most STIs remain undetected and untreated due to standard practice syndromic management in accordance with World Health Organization (WHO) guidelines. Although lab-based and point-of-care molecular tests are available, optimal screening strategies during pregnancy, their health impact, and cost-effectiveness are unknown. METHODS : We will implement a 3-arm (1:1:1) type-1 hybrid effectiveness-implementation randomized-controlled trial (RCT). We will enroll 2500 pregnant women attending their first antenatal care (ANC) visit for their current pregnancy at participating health facilities in Buffalo City Metro District, Eastern Cape Province, South Africa. Participants allocated to arms 1 and 2 (intervention) will receive GeneXpert® point-of-care diagnostic testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, with same-day treatment for detected infection(s). Arm 1 will additionally receive a test-of-cure 3 weeks post-treatment, while Arm 2 will receive a repeat test at 30–34 weeks’ gestation. Those allocated to Arm 3 will receive syndromic management (standard-of-care). The RE-AIM framework will be used to guide collection of implementation indicators to inform potential future scale up. Primary outcome measures include (1) frequency of adverse birth outcomes among study arms, defined by a composite measure of low birth weight and pre-term delivery, and (2) change in STI prevalence between baseline and birth outcome among intervention arms and compared to standard-of-care. Estimates and comparative costs of the different screening strategies relative to standard-of-care and the costs of managing adverse birth outcomes will be calculated. Costeffectiveness will be assessed per STI and disability-adjusted life year averted. DISCUSSION : This trial is the first RCT designed to identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes. Demonstrating the impact of diagnostic screening and treatment, compared to syndromic management, on birth outcomes will provide critical evidence to inform changes to WHO guidelines for syndromic management of STIs during pregnancy. TRIAL REGISTRATION : ClinicalTrials.gov NCT04 446611. Registered on 25 June 2020.The US National Institutes of Health.https://trialsjournal.biomedcentral.com/am2023Medical Microbiolog

Mixed-methods evaluation of mental healthcare integration into tuberculosis and maternal-child healthcare services of four South African districts

Abstract Background The South African National Mental Health Policy Framework and Strategic Plan 2013–2020 was adopted to address the country’s substantial burden and inadequate treatment of mental illness. It outlines measures toward the goal of full integration of mental health services into primary care by 2020. To evaluate progress and challenges in implementation, we conducted a mixed-methods assessment of mental health service provision in tuberculosis and maternal-child healthcare services of four districts in South Africa. Methods Forty clinics (ten per district) were purposively selected to represent both urban and rural locations. District-level program managers (DPMs) for mental health, tuberculosis, and maternal-child healthcare were qualitatively interviewed about district policy and procedures for management of mental illness and challenges in integrating mental health services into primary care. Clinic nurses and mental health practitioners (MHPs) completed a quantitative questionnaire to assess their engagement with stepped care for patients with mental illness. Qualitative and quantitative data were collected concurrently and compared to triangulate progress in implementation of integrated services. Results A total of 59 nurses and 17 MHPs completed questionnaires, and nine DPMs were interviewed (total n = 85). DPMs indicated that nurses should screen for mental illness at every patient visit, although only 43 (73%) nurses reported conducting universal screening and 26 (44%) reported using a specific screening tool. For patients who screen positive for mental illness, DPMs described a stepped-care approach in which MHPs diagnose patients and then treat or refer them to specialized care. However, only 7 (41%) MHPs indicated that they diagnose mental illness and 14 (82%) offer any treatment for mental illness. Addressing challenges to current integration efforts, DPMs highlighted 1) insufficient funding and material resources, 2) poor coordination at the district administrative level, and 3) low mental health awareness in district administration and the general population. Conclusions Though some progress has been made toward integration of mental health services into primary care settings, there is a substantial lack of training and clarity of roles for nurses and MHPs. To enhance implementation, increased efforts must be directed toward improving district-level administrative coordination, mental health awareness, and financial and material resources