A trial of nurturing care among children who are HIV-exposed and uninfected in eSwatini.

INTRODUCTION: Children who are HIV-exposed and uninfected (CHEU) are a growing population at potential risk of poor neurocognitive development. We tested a nurturing care intervention on children's neurocognitive development and maternal depressive symptoms (primary) with mediation through caregiving activities (secondary). METHODS: This study was conducted among six intervention and nine comparison antenatal-care/prevention of vertical transmission (ANC/PVT) HIV clinics in eSwatini. We enrolled pregnant women and measured infant development at 9 and 18 months. mothers2mothers (m2m) designed and implemented the clinic-home-community-based intervention. We measured infants' neurodevelopment, maternal depressive symptoms and caregiving activities with the Mullen Scales of Early Learning (MSEL), Edinburgh Postnatal Depression Scale, HOME Inventory and Family Care Indicators. We fitted linear mixed effects regression models with clinic random effects to compare intervention versus comparison arms, and generalised structural equation models to evaluate mediation, adjusting for confounders. RESULTS: Mother-infant pairs (n = 429) participated between January 2016 through May 2018. Socio-demographic characteristics were balanced between arms except for higher rates of peri-urban versus rural residence and single versus married mothers in the comparison group. The 18 month retention was 82% (180/220) intervention, 79% (166/209) comparison arm, with 25 infant deaths. Intervention MSEL scores were significantly, and modestly, higher in receptive language (55.7 [95% CI 54.6, 56.9] vs. 53.7 [95% CI 52.6, 54.8]), expressive language (42.5 [95% CI 41.6, 39.8] vs. 40.8 [95% CI 39.8, 41.7]) and composite MSEL (85.4 [95% CI 83.7, 84.5] vs. 82.7 [95% CI 81.0, 84.5]), with no difference in maternal depressive symptoms or in observations of mother-child interactions. Intervention book-sharing scores were higher (0.63 vs. 0.41) and mediated the effect on MSEL scores (indirect effect, p-values ≤ 0.024). The direct effects on visual reception and expressive language scores were significantly higher in the intervention compared to the comparison arm (coefficients 1.93 [95% CI 0.26, 3.60] and 1.66 [95% CI 0.51, 2.79, respectively]). CONCLUSIONS: Nurturing care interventions can be integrated into ANC/PVT clinic-home-community programmes. The intervention, mediated through interactive caregiving activities, increased language development scores among CHEU. Partnering with a local team, m2m, to design and implement a culturally relevant intervention illustrates the ability to impact parent-child play and learning activities that are associated with children's neurodevelopment.

Postnatal clubs: Implementation of a differentiated and integrated model of care for mothers living with HIV and their HIV-exposed uninfected babies in Cape Town, South Africa.

BACKGROUND: Despite the overall reduction in the HIV mother-to-child transmission (MTCT) rate in South Africa, poor adherence and retention in care during breastfeeding contribute to this period being a major driver of MTCT in South Africa. To improve this retention, postnatal clubs were created as an integrated, differentiated model of care providing psychosocial support and comprehensive care for the mother-infant pairs (MIP), including HIV and under-5-child services. We describe the implementation of these facility-based clubs and examine its health outcomes in a peri-urban primary health care setting in Cape Town, South Africa. METHODS: In this prospective cohort study, conducted between June 2016 and December 2019, MIPs were recruited into postnatal clubs between 6 weeks and 6 months of age and followed-up until 18 months of age. Outcomes including maternal Viral Load (VL), and children's HIV testing were compared to a historical control group. Children's immunizations and maternal sexual and reproductive health outcomes are also described. RESULTS: During the implementation of the postnatal club study period, 484 MIP were recruited with 84% overall attendance, 95% overall viral load suppression, and 98% overall uptake of HIV infant testing. Compared to historical controls, the club infant rapid test uptake was 1.6 times higher (95% CI: 1.4-1.9) at 9 months and 2.0 times higher at 18 months (95% CI: 1.6-2.6). Through 12 months and between 12-18 months, maternal VL monitoring was higher in the club group compared to the historical control by 1.5 times (95% CI: 1.3-1.6) and 2.6 times (95% CI: 2.1-3.2), respectively, with similar maternal VL suppression. Of 105 infants attending the 12 months visit, 99% were fully vaccinated by one year. CONCLUSION: MIP in the postnatal clubs showed better PMTCT outcomes than historical controls with high levels of retention in care. Other outcomes such as immunisation results suggest that integration of services, such as in the postnatal club, is feasible and beneficial for MIPs.

High-throughput Screening for Defense Priming-inducing Compounds in Parsley Cell Cultures.

Defense priming describes the enhanced potency of cells to activate defense responses. Priming accompanies local and systemic immune responses and can be triggered by microbial infection or upon treatment with certain chemicals. Thus, chemically activating defense priming is promising for biomedicine and agriculture. However, test systems for spotting priming-inducing chemicals are rare. Here, we describe a high-throughput screen for compounds that prime microbial pattern-spurred secretion of antimicrobial furanocoumarins in parsley culture cells. For the best possible throughput, we perform the assay with 1-ml aliquots of cell culture in 24-well microtiter plates. The advantages of the non-invasive test over competitive assays are its simplicity, remarkable reliability, and high sensitivity, which is based on furanocoumarin fluorescence in UV light.

An illuminated respiratory activity monitoring system identifies priming-active compounds in plant seedlings.

BACKGROUND: Growing large crop monocultures and heavily using pesticides enhances the evolution of pesticide-insensitive pests and pathogens. To reduce pesticide use in crop cultivation, the application of priming-active compounds (PrimACs) is a welcome alternative. PrimACs strengthen the plant immune system and could thus help to protect plants with lower amounts of pesticides. PrimACs can be identified, for example, by their capacity to enhance the respiratory activity of parsley cells in culture as determined by the oxygen transfer rate (OTR) using the respiration activity monitoring system (RAMOS) or its miniaturized version, µRAMOS. The latter was designed for with suspensions of bacteria and yeast cells in microtiter plates (MTPs). So far, RAMOS or µRAMOS have not been applied to adult plants or seedlings, which would overcome the limitation of (µ)RAMOS to plant suspension cell cultures. RESULTS: In this work, we introduce a modified µRAMOS for analysis of plant seedlings. The novel device allows illuminating the seedlings and records the respiratory activity in each well of a 48-well MTP. To validate the suitability of the setup for identifying novel PrimAC in Arabidopsis thaliana, seedlings were grown in MTP for seven days and treated with the known PrimAC salicylic acid (SA; positive control) and the PrimAC candidate methyl 1-(3,4-dihydroxyphenyl)-2-oxocyclopentane-1-carboxylate (Tyr020). Twenty-eight h after treatment, the seedlings were elicited with flg22, a 22-amino acid peptide of bacterial flagellin. Upon elicitation, the respiratory activity was monitored. The evaluation of the OTR course reveals Tyr020 as a likely PrimAC. The priming-inducing activity of Tyr020 was confirmed using molecular biological analyses in A. thaliana seedlings. CONCLUSION: We disclose the suitability of µRAMOS for identifying PrimACs in plant seedlings. The difference in OTR during a night period between primed and unprimed plants was distinguishable after elicitation with flg22. Thus, it has been shown that the µRAMOS device can be used for a reliable screening for PrimACs in plant seedlings.

Community surveillance and response to maternal and child deaths in low- and middle-income countries: A scoping review.

BACKGROUND: Civil registration and vital statistics (CRVS) systems do not produce comprehensive data on maternal and child deaths in most low- and middle-income countries (LMICs), with most births and deaths which occur outside the formal health system going unreported. Community-based death reporting, investigation and review processes are being used in these settings to augment official registration of maternal and child deaths and to identify death-specific factors and associated barriers to maternal and childcare. This study aims to review how community-based maternal and child death reporting, investigation and review processes are carried out in LMICs. METHODS: We conducted a scoping review of the literature published in English from January 2013 to November 2020, searching PubMed, EMBASE, PsycINFO, Joanna Briggs, The Cochrane Library, EBM reviews, Scopus, and Web of Science databases. We used descriptive analysis to outline the scope, design, and distribution of literature included in the study and to present the content extracted from each article. The scoping review is reported following the PRISMA reporting guideline for systematic reviews. RESULTS: Of 3162 screened articles, 43 articles that described community-based maternal and child death review processes across ten countries in Africa and Asia were included. A variety of approaches were used to report and investigate deaths in the community, including identification of deaths by community health workers (CHWs) and other community informants, reproductive age mortality surveys, verbal autopsy, and social autopsy. Community notification of deaths by CHWs complements registration of maternal and child deaths missed by routinely collected sources of information, including the CRVS systems which mostly capture deaths occurring in health facilities. However, the accuracy and completeness of data reported by CHWs are sub-optimal. CONCLUSIONS: Community-based death reporting complements formal registration of maternal and child deaths in LMICs. While research shows that community-based maternal and child death reporting was feasible, the accuracy and completeness of data reported by CHWs are sub-optimal but amenable to targeted support and supervision. Studies to further improve the process of engaging communities in the review, as well as collection and investigation of deaths in LMICs, could empower communities to respond more effectively and have a greater impact on reducing maternal and child mortality.

Engaging community health workers in maternal and infant death identification in Khayelitsha, South Africa: a pilot study.

BACKGROUND: Engaging community health workers in a formalised death review process through verbal and social autopsy has been utilised in different settings to estimate the burden and causes of mortality, where civil registration and vital statistics systems are weak. This method has not been widely adopted. We piloted the use of trained community health workers (CHW) to investigate the extent of unreported maternal and infant deaths in Khayelitsha and explored requirements of such a programme and the role of CHWs in bridging gaps. METHODS: This was a mixed methods study, incorporating both qualitative and quantitative methods. Case identification and data collection were done by ten trained CHWs. Quantitative data were collected using a structured questionnaire. Qualitative data were collected using semi-structured interview guides for key informant interviews, focus group discussions and informal conversations. Qualitative data were analysed thematically using a content analysis approach. RESULTS: Although more than half of the infant deaths occurred in hospitals (n = 11/17), about a quarter that occurred at home (n = 4/17) were unreported. Main causes of deaths as perceived by family members of the deceased were related to uncertainty about the quality of care in the facilities, socio-cultural and economic contexts where people lived and individual factors. Most unreported deaths were further attributed to weak facility-community links and socio-cultural practices. Fragmented death reporting systems were perceived to influence the quality of the data and this impacted on the number of unreported deaths. Only two maternal deaths were identified in this pilot study. CONCLUSIONS: CHWs can conduct verbal and social autopsy for maternal and infant deaths to complement formal vital registration systems. Capacity development, stakeholder's engagement, supervision, and support are essential for a community-linked death review system. Policymakers and implementers should establish a functional relationship between community-linked reporting systems and the existing system as a starting point. There is a need for more studies to confirm or build on our pilot findings.

Peer Support for Adolescents and Young People Living with HIV in sub-Saharan Africa: Emerging Insights and a Methodological Agenda.

PURPOSE: Despite clear need and disproportionate risk, adolescents, and young people living with HIV (AYPLHIV) are underserved within the HIV response. "Peer support" increasingly forms part of adolescent and youth-responsive service packages as a class of implementation strategies that can support adolescents to access, engage, and sustain treatment. This paper examines examples of peer support for AYPLHIV within sub-saharan Africa to explore the determinants of successful implementation, outcomes and scale-up, as well as policy and programmatic implications. RECENT FINDINGS: Although adolescent peer support has been observed to be widely implemented, there are few examples of detailed program descriptions describing operational logistics or outcomes around peer support interventions. Nevertheless the few examples available provide preliminary support for the potential utility of peer support to improve AYPLHIV outcomes. Implementation science research is an urgent imperative to examine applicability of peer support for this priority population. In the meantime, programs should move forward with implementation based on promising outcomes, programmatic experience, contextual understanding of challenges and gaps, and best practice examples.

Effect of a Mentor Mother Programme on retention of mother-baby pairs in HIV care: A secondary analysis of programme data in Uganda.

BACKGROUND: Community healthcare workers (CHWs) play an important role in promoting HIV-care retention. Notwithstanding inconsistencies in the outcomes of CHW programmes, these programmes are known to have a positive effect on retention of mother-baby pairs in HIV-care in sub-Saharan Africa. AIM: The aim of this analysis was to assess the effect of mothers2mothers (m2m) Ugandan Mentor Mother (MM) programme on the retention of mother-baby pairs in HIV-care. METHODS: We conducted a secondary analysis of data obtained from the m2m Uganda MM programme in nine East Central districts. The primary data was generated through a quasi-experimental study of women attending prevention of mother to child transmission of HIV (PMTCT) clinics in Uganda between January 2011 and March 2014; where those who were enrolled at PMTCT sites with the MM intervention (n = 1161) were compared with those who received standard PMCTCT services without the MM intervention (n = 1143). Frequencies and descriptive statistics were calculated for categorical and continuous measures respectively. Risk factors for retention in care were determined by clustered generalised estimating equations and reported as adjusted odds ratios (AOR) with 95% confidence intervals (95% CI). RESULTS: Retention in the PMTCT cascade was significantly higher for mother-baby pairs in the intervention arm compared to those in the control arm across all measured time points (96.7% vs 65.8% at 6 weeks after birth, p<0.001; 81.5% vs 42% at 6 weeks after cessation of breastfeeding, p<0.001; and 71.2% vs 20.6% at 18 months after birth, p<0.001). Relative to the control group, women in the intervention group were less likely to be lost to follow up following treatment initiation (AOR 0.05, 95% CI: 0.02, 0.15). There was no difference in the proportion of the retained mother-baby pairs who received prescribed PMTCT interventions at different time points but a significantly higher number of mother-baby pairs in the intervention arm were retained at different time points. CONCLUSION: HIV positive mothers and their HIV exposed children in the mothers2mothers Ugandan Mentor Mother programme had higher retention in HIV care at every step along the PMTCT cascade. We therefore recommend adoption of this peer-to-peer model in sub-Saharan Africa to complement retention in care strategies and health system interventions especially among priority and key populations.

Impact of lay health worker programmes on the health outcomes of mother-child pairs of HIV exposed children in Africa: A scoping review.

BACKGROUND: Increased demand for healthcare services in countries experiencing high HIV disease burden and often coupled with a shortage of health workers, has necessitated task shifting from professional health workers to Lay Health Workers (LHWs) in order to improve healthcare delivery. Maternal and Child Health (MCH) services particularly benefit from task-shifting to LHWs or similar cadres. However, evidence on the roles and usefulness of LHWs in MCH service delivery in Sub-Saharan Africa (SSA) is not fully known. OBJECTIVES: To examine evidence of the roles and impact of lay health worker programmes focusing on Women Living with HIV (WLH) and their HIV-exposed infants (HEIs). METHODS: A scoping review approach based on Arksey and O'Malley's guiding principles was used to retrieve, review and analyse existing literature. We searched for articles published between January 2008 and July 2018 in seven (7) databases, including: MEDLINE, Embase, PsycINFO, Joanna Briggs, The Cochrane Library, EBM reviews and Web of Science. The critical constructs used for the literature search were "lay health worker", "community health worker", "peer mentor", "mentor mother," "Maternal and Child health worker", "HIV positive mothers", "HIV exposed infants" and PMTCT. RESULTS: Thirty-three (33) full-text articles meeting the eligibility criteria were identified and included in the final analysis. Most (n = 13, 39.4%) of the included studies were conducted in South Africa and used a cluster RCT design (n = 13, 39.4%). The most commonly performed roles of LHWs in HIV specific MCH programmes included: community engagement and sensitisation, psychosocial support, linkage to care, encouraging women to bring their infants back for HIV testing and supporting default tracing. Community awareness on Mother to Child Transmission of HIV (MTCT), proper and consistent use of condoms, clinic attendance and timely HIV testing of HEIs, as well as retention in care for infected persons, have all improved because of LHW programmes. CONCLUSION: LHWs play significant roles in the management of WLH and their HEIs, improving MCH outcomes in the process. LHW interventions are beneficial in increasing access to PMTCT services and reducing MTCT of HIV, though their impact on improving adherence to ART remains scanty. Further research is needed to evaluate ART adherence in LHW interventions targeted at WLH. LHW programmes can be enhanced by increasing supportive supervision and remuneration of LHWs.

Realizing the Promise of the Global Plan: Engaging Communities and Promoting the Health and Human Rights of Women Living With HIV.

The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive highlighted the need to put the health and well-being of women and mothers at the center of efforts to prevent vertical transmission. This article will examine a selection of community engagement practices in 3 key areas: (1) as an accountability tool, (2) in service delivery, and (3) as a facilitator of human rights. The lived experiences of women living with HIV as recipients of and participants in services for the prevention of vertical transmission provide both the framework for an exploration of best community engagement practices and suggestions for the way forward.

Late deterioration of left ventricular function after right ventricular pacemaker implantation.

OBJECTIVES: Right ventricular (RV) pacing induces a left bundle branch block pattern on ECG and may promote heart failure. Patients with dual chamber pacemakers (DCPs) who present with progressive reduction in left ventricular ejection fraction (LVEF) secondary to RV pacing are candidates for cardiac resynchronization therapy (CRT). This study analyzes whether upgrading DCP to CRT with the additional implantation of a left ventricular (LV) lead improves LV function in patients with reduced LVEF following DCP implantation. METHODS: Twenty-two patients (13 males) implanted with DCPs and a high RV pacing percentage (>90%) were evaluated in term of new-onset heart failure symptoms. The patients were enrolled in this retrospective single-center study after obvious causes for a reduced LVEF were excluded with echocardiography and coronary angiography. In all patients, DCPs were then upgraded to biventricular devices. LVEF was analyzed with a two-sided t-test. QRS duration and brain natriuretic peptide (BNP) levels were analyzed with the unpaired t-test. RESULTS: LVEF declined after DCP implantation from 54±10% to 31±7%, and the mean QRS duration was 161±20 ms during RV pacing. NT-pro BNP levels were elevated (3365±11436 pmol/L). After upgrading to a biventricular device, a biventricular pacing percentage of 98.1±2% was achieved. QRS duration decreased to 108±16 ms and 106±20 ms after 1 and 6 months, respectively. There was a significant increase in LVEF to 38±8% and 41±11% and a decrease in NT-pro BNP levels to 3088±2326 pmol/L and 1860±1838 pmol/L at 1 and 6 months, respectively. CONCLUSION: Upgrading to CRT may be beneficial in patients with DCPs and heart failure induced by a high RV pacing percentage.