Pneumococcal conjugate vaccine induced IgG and nasopharyngeal carriage of pneumococci: Hyporesponsiveness and immune correlates of protection for carriage

BACKGROUND: Prior studies have demonstrated hyporesponsiveness to pneumococcal conjugate vaccines (PCVs) when administered in the presence of homologous carriage. This may be substantially more important in Africa where carriage prevalence is high. Deriving a correlate of protection (CoP) for carriage is important in guiding the future use of extended PCVs as population control of pneumococcal disease by vaccination is now focused principally on its indirect effect. We therefore explored the complex relationship between existing carriage and vaccine responsiveness, and between serum IgG levels and risk of acquisition. METHODS: We undertook secondary analyses of data from two previously published clinical trials of the safety and immunogenicity of PCV in Kenya. We compared responses to vaccination between serotype-specific carriers and non-carriers at vaccination. We assessed the risk of carriage acquisition in relation to PCV-induced serum IgG levels using either a step- or continuous-risk function. RESULTS: For newborns, the immune response among carriers was 51–82% lower than that among non-carriers, depending on serotype. Among toddlers, for serotypes 6B, 14 and 19F the post-vaccination response among carriers was lower by between 29 and 70%. The estimated CoP against acquisition ranged from 0.26 to 1.93 μg/mL across serotypes, however, these thresholds could not be distinguished statistically from a model with constant probability of carriage independent of assay value. CONCLUSION: We have confirmed hyporesponsiveness in an equatorial African setting in both infants and toddlers. Population responses to vaccination are likely to improve with time as carriage prevalence of vaccine serotypes is reduced. We have not found clear correlates of protection against carriage acquisition among toddlers in this population. Assessing the potential of new vaccines through the use of CoP against carriage is still difficult as there are no clear-cut serotype specific correlates

The Systems Analysis and Improvement Approach: specifying core components of an implementation strategy to optimize care cascades in public health.

This work was supported from grants from the National Institutes of Health, including R01MH113435 (SAIA-SCALE), F32HD088204 and R34AI129900 (SAIA-PEDS), R21AI124399 (mPCAT), K24HD088229 (SAIA-FP), R21MH113691 (SAIA-MH), P30AI027757 (CFAR), R21DA046703 (SAIA-Naloxone), R01HL142412 (SAIA-HTN), 1UG3HL156390-01 (SCALE SAIA-HTN) R01HD0757 and R01HD0757-02S1 (SAIA), K08CA228761 (CCS SAIA) and T32AI070114 (UNC TIDE), Support was provided by the Implementation Science Core of the University of Washington/Fred Hutch Center for AIDS Research, an NIH-funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK. This work was also supported by the Doris Duke Charitable Foundation and the Rita and Alex Hillman Foundation (SAIA-JUV), and the Thrasher Foundation (SAIA-MAL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Doris Duke Charitable Foundation, the Rita and Alex Hillman Foundation, or the Thrasher Foundation. © 2023. The Author(s). Publisher Copyright: © 2023, The Author(s). © 2023. The Author(s).BACKGROUND: Healthcare systems in low-resource settings need simple, low-cost interventions to improve services and address gaps in care. Though routine data provide opportunities to guide these efforts, frontline providers are rarely engaged in analyzing them for facility-level decision making. The Systems Analysis and Improvement Approach (SAIA) is an evidence-based, multi-component implementation strategy that engages providers in use of facility-level data to promote systems-level thinking and quality improvement (QI) efforts within multi-step care cascades. SAIA was originally developed to address HIV care in resource-limited settings but has since been adapted to a variety of clinical care systems including cervical cancer screening, mental health treatment, and hypertension management, among others; and across a variety of settings in sub-Saharan Africa and the USA. We aimed to extend the growing body of SAIA research by defining the core elements of SAIA using established specification approaches and thus improve reproducibility, guide future adaptations, and lay the groundwork to define its mechanisms of action. METHODS: Specification of the SAIA strategy was undertaken over 12 months by an expert panel of SAIA-researchers, implementing agents and stakeholders using a three-round, modified nominal group technique approach to match core SAIA components to the Expert Recommendations for Implementing Change (ERIC) list of distinct implementation strategies. Core implementation strategies were then specified according to Proctor's recommendations for specifying and reporting, followed by synthesis of data on related implementation outcomes linked to the SAIA strategy across projects. RESULTS: Based on this review and clarification of the operational definitions of the components of the SAIA, the four components of SAIA were mapped to 13 ERIC strategies. SAIA strategy meetings encompassed external facilitation, organization of provider implementation meetings, and provision of ongoing consultation. Cascade analysis mapped to three ERIC strategies: facilitating relay of clinical data to providers, use of audit and feedback of routine data with healthcare teams, and modeling and simulation of change. Process mapping matched to local needs assessment, local consensus discussions and assessment of readiness and identification of barriers and facilitators. Finally, continuous quality improvement encompassed tailoring strategies, developing a formal implementation blueprint, cyclical tests of change, and purposefully re-examining the implementation process. CONCLUSIONS: Specifying the components of SAIA provides improved conceptual clarity to enhance reproducibility for other researchers and practitioners interested in applying the SAIA across novel settings.Peer reviewe

Providing “a beam of light to see the gaps”: determinants of implementation of the Systems Analysis and Improvement Approach applied to the pediatric and adolescent HIV cascade in Kenya

Abstract Background Children and adolescents living with HIV have poorer rates of HIV testing, treatment, and virologic suppression than adults. Strategies that use a systems approach to optimize these multiple, linked steps simultaneously are critical to close these gaps. Methods The Systems Analysis and Improvement Approach (SAIA) was adapted and piloted for the pediatric and adolescent HIV care and treatment cascade (SAIA-PEDS) at 6 facilities in Kenya. SAIA-PEDS includes three tools: continuous quality improvement (CQI), flow mapping, and pediatric cascade analysis (PedCAT). A predominately qualitative evaluation utilizing focus group discussions (N = 6) and in-depth interviews (N = 19) was conducted with healthcare workers after implementation to identify determinants of implementation. Data collection and analysis were grounded in the Consolidated Framework for Implementation Research (CFIR). Results Overall, the adapted SAIA-PEDS strategy was acceptable, and the three tools complemented one another and provided a relative advantage over existing processes. The flow mapping and CQI tools were compatible with existing workflows and resonated with team priorities and goals while providing a structure for group problem solving that transcended a single department’s focus. The PedCAT was overly complex, making it difficult to use. Leadership and hierarchy were complex determinants. All teams reported supportive leadership, with some describing in detail how their leadership was engaged and enthusiastic about the SAIA-PEDS process, by providing recognition, time, and resources. Hierarchy was similarly complex: in some facilities, leadership stifled rapid innovation by insisting on approving each change, while at other facilities, leadership had strong and supportive oversight of processes, checking on the progress frequently and empowering teams to test innovative ideas. Conclusion CQI and flow mapping were core components of SAIA-PEDS, with high acceptability and consistent use, but the PedCAT was too complex. Leadership and hierarchy had a nuanced role in implementation. Future SAIA-PEDS testing should address PedCAT complexity and further explore the modifiability of leadership engagement to maximize implementation