A multi-step analysis and co-produced principles to support equitable partnership with Liverpool School of Tropical Medicine, 125 years on.

Transboundary health partnerships are shaped by global inequities. Perspectives from the "global South" are critical to understand and redress power asymmetries in research partnerships yet are not often included in current guidelines. We undertook research with partners working with the Liverpool School of Tropical Medicine (LSTM) to inform LSTM's equitable partnership strategy and co-develop principles for equitable partnerships as an entry point towards broader transformative action on research partnerships. We applied mixed-methods and participatory approaches. An online survey (n = 21) was conducted with LSTM's transboundary partners on fairness of opportunity, fair process, and fair sharing of benefits, triangulated with key informant interviews (n = 12). Qualitative narratives were analysed using the thematic framework approach. Findings were presented in a participatory workshop (n = 11) with partners to co-develop principles, which were refined and checked with stakeholders. Early inclusion emerged as fundamental to equitable partnerships, reflected in principle one: all partners to input into research design, agenda-setting and outputs to reflect priorities. Transparency is highlighted in principle two to guide all stages including agenda-setting, budgeting, data ownership and authorship. Principle three underscores the importance of contextually embedded knowledge for relevant and impactful research. Multi-directional capacity strengthening across all cadres is highlighted in principle four. Principle five includes LSTM leveraging their position for strategic and deliberate promotion of transboundary partners in international forums. A multi-centric model of partnership with no centralised power is promoted in principle six. Finally, principle seven emphasises commitment to the principles and Global Code of Conduct values: Fairness, Respect, Care, Honesty. The co-developed principles are part of ongoing reflections and dialogue to improve and undo harmful power structures that perpetuate coloniality within global health. While this process was conducted with LSTM-Liverpool's existing partners, the principles to strengthen equity are applicable to other institutions engaged in transboundary research partnerships and relevant for funders.

The development, implementation, and evaluation of an optimal model for the case detection, referral, and case management of Neglected Tropical Diseases.

BACKGROUND: People affected by Neglected Tropical Diseases (NTDs), specifically leprosy, Buruli ulcer (BU), yaws, and lymphatic filariasis, experience significant delays in accessing health services, often leading to catastrophic physical, psychosocial, and economic consequences. Global health actors have recognized that Sustainable Development Goal 3:3 is only achievable through an integrated inter and intra-sectoral response. This study evaluated existing case detection and referral approaches in Liberia, utilizing the findings to develop and test an Optimal Model for integrated community-based case detection, referral, and confirmation. We evaluate the efficacy of implementing the Optimal Model in improving the early diagnosis of NTDs, thus minimizing access delays and reducing disease burden. METHODS: We used a participatory action research approach to develop, implement, and evaluate an Optimal Model for the case detection, referral, and management of case management NTDs in Liberia. We utilized qualitative and quantitative methods throughout the cycle and implemented the model for 12 months. RESULTS: During the implementation of our optimal model, the annual number of cases detected increased compared to the previous year. Cases were detected at an earlier stage of disease progression, however; gendered dynamics in communities shape the case identification process for some individuals. Qualitative data showed increased knowledge of the transmission, signs, symptoms, and management options among community health workers (CHW). CONCLUSION: The results provide evidence of the benefits of an integrated approach and the programmatic challenges to improve access to health services for persons affected by NTDs. The effectiveness of an integrated approach depends on a high level of collaboration, joint planning, and implementation embedded within existing health systems infrastructure.

A holistic approach to well-being and neglected tropical diseases: evaluating the impact of community-led support groups in Nigeria using community-based participatory research.

BACKGROUND: Neglected tropical diseases (NTDs) affect around 1 billion people, many living in the poorest parts of the world. NTDs often lead to serious long-term physical impairments. Stigma, disability, poverty and social isolation interact, resulting in poor quality of life and significant psychosocial impacts. The holistic health and psychosocial needs of persons affected by NTDs are often overlooked in integrated NTD programme design and research. Furthermore, the viewpoints of persons affected are often absent and spaces for empowerment and advocacy are limited. METHODS: Using a community-based participatory research design, our study partnered with persons affected and caregivers as co-researchers to address this gap. Through the process, we co-designed and implemented community-based support groups in Kaduna and Kwara, Nigeria, where NTDs are endemic. This paper utilises photovoice with support group facilitators (persons affected); participant observation of group meetings; rapid micronarratives with support group members; and key informant interviews with programme implementers at the state and local government area levels to explore the impact of the support groups from the perspective of people affected by NTDs and other health system actors. RESULTS: Perceived impacts of the support groups included a sense of ownership and empowerment, stigma reduction, improved self-esteem, improved health knowledge and health outcomes and capacity strengthening through vocational training. CONCLUSIONS: Support groups, as community spaces of healing, offer a low-cost holistic intervention for chronic disease and disability.

A mixed methods evaluation of an integrated training package for skin neglected tropical diseases in Kaduna and Ogun, Nigeria.

BACKGROUND: The overall burden of neglected tropical diseases (NTDs) affecting the skin is undetermined. Skin conditions are among the top 10 causes of disability worldwide. Affected persons seek treatment at advanced stages of the disease, resulting in morbidity and disability. We developed and evaluated an integrated training intervention for early case detection, referral and management of skin NTDs in two states in Nigeria. METHODS: This was a mixed-methods study using participatory approaches to develop specific skin algorithms and training packages for community and primary level health workers. This supported the identification, referral and clinical diagnosis of suspected cases. We used Kirkpatrick's model to evaluate the training package. RESULTS: Participants' knowledge improved after the 2-months intervention. Across both states, knowledge retention appeared more robust for cadres at all levels: state, local government area and primary healthcare. All (100%) participants mentioned that the training assisted them in detecting, referring and managing skin NTDs. Training was understood by participants and training materials were easy to understand. Materials were also effective in educating community members about the symptoms of NTDs and supported referral to facilities for appropriate management. CONCLUSIONS: Community implementers can be trained and supervised to detect people affected by skin NTDs and support appropriate management within the existing patient care pathway.

Exploring the impact of COVID-19 on frontline health workers through a photovoice study in Kaduna, Kwara and Ogun States, Nigeria.

BACKGROUND: Described as the 'backbone of health systems', particularly in low- and middle-income countries, community health workers (CHWs) are a critical cadre on the frontline of any outbreak response. However, it is widely recognised that CHWs are frequently lacking in appropriate support from the health system due to inadequate physical, social and financial resources. Furthermore, despite their critical role in service delivery, the health and well-being of CHWs is seldom considered and the additional emotional and physical burdens that health systems shocks can present are frequently ignored. Thus a critical step in strengthening health systems to manage disease outbreaks or other system shocks is to ensure that CHWs are adequately supported. Within this study we document the experiences of CHWs within Nigeria during the coronavirus disease 2019 (COVID-19) outbreak to understand the impact of the pandemic on CHW well-being with a view to identifying strategies that could support CHWs during COVID-19 and subsequent health system shocks. METHODS: This study was based in Ogun, Kaduna and Kwara States, Nigeria. We used the creative participatory methodology of photovoice with 30 CHWs (10 in each state). Participants were asked to take photos documenting their experiences of working and living through the pandemic. Participants sent photos with captions to the research team via WhatsApp following one-on-one discussions. Photos were co-analysed among participants in focus group discussions using thematic analysis. RESULTS: Our findings reveal similar experiences of CHWs across Ogun, Kwara and Kaduna States in Nigeria, providing a unique insight into how the Nigerian health system was impacted and how this closely aligns to the performance and well-being of CHWs. CHW experiences related to three overarching themes: major stressors and challenges experienced due to COVID-19 (fear of contracting COVID-19, food insecurity, personal and gendered impacts), the impact of COVID-19 on providing routine care (stigma from community members, heavy workloads and inadequate equipment provision) and motivation and support from the community (pride in their roles and valued support from community leaders). The challenges highlighted through photovoice led to developing recommendations to address some of the challenges. This included training, adequate resource provision, routine supervision and peer support. CONCLUSIONS: COVID-19 highlighted the burden health workers often face. Photovoice allowed a space for frontline health workers to come together to share common experiences, particularly the psychosocial impact of working during health system shocks and its impact on performance. This underlines the need to acknowledge mental health and prioritise the well-being of healthcare staff. Sharing stories from the perspectives of health workers provides a platform to share learning and strategies on how to best support health workers holistically, particularly during health system shocks.

Exploring the well-being of people affected by skin NTDs in Kaduna and Kwara States, Nigeria: a photovoice and scoping review study.

People affected by skin neglected tropical diseases (NTDs) grapple with both physical and emotional reactions that compromise their health and well-being. Multiple studies with people affected by skin NTDs have shown high levels of poor mental well-being using self-report questionnaires or psychological measures. However, few have provided in-depth documentation of lived experiences from the perspective of affected persons and there is limited consideration of how their viewpoints can be used to shape intervention design. This article draws together findings from an international scoping review and a photovoice study conducted in Kaduna and Kwara States, Nigeria. Our combined analysis, which situates the lived realities of people affected by skin NTDs within the existing evidence base, was used to inform the design of a subsequent well-being intervention. Using Meyer's (2003) minority stress model, we have illustrated that there is a synergistic relationship between mental health, chronic morbidity and disability from skin NTDs. This relationship results from a complex interplay of factors including pain and discomfort and a reduced ability to function and participate in areas such as livelihoods, food provision and education. Stigma and discrimination act as a catalyst for these functional limitations and participation restrictions, resulting in feelings of being useless, broken, shame and sadness. The critical role of participatory methods in our study emphasises how people affected by skin NTDs have multiple coping mechanisms that can be galvanised in the provision of holistic NTD care. We recommend that NTD programmes should strengthen relationships with affected persons to identify pre-existing support platforms that can be used to support the emotional and physical health and well-being of affected persons. Working with affected persons and community actors to strengthen necessary intersectoral approaches is a first step in designing and delivering such holistic care.

Qualitative study exploring lessons from Liberia and the UK for building a people-centred resilient health systems response to COVID-19.

INTRODUCTION: COVID-19 has tested the resilience of health systems globally and exposed existing strengths and weaknesses. We sought to understand health systems COVID-19 adaptations and decision making in Liberia and Merseyside, UK. METHODS: We used a people-centred approach to carry out qualitative interviews with 24 health decision-makers at national and county level in Liberia and 42 actors at county and hospital level in the UK (Merseyside). We explored health systems' decision-making processes and capacity to adapt and continue essential service delivery in response to COVID-19 in both contexts. RESULTS: Study respondents in Liberia and Merseyside had similar experiences in responding to COVID-19, despite significant differences in health systems context, and there is an opportunity for multidirectional learning between the global south and north. The need for early preparedness; strong community engagement; clear communication within the health system and health service delivery adaptations for essential health services emerged strongly in both settings. We found the Foreign, Commonwealth and Development Office (FCDO) principles to have value as a framework for reviewing health systems changes, across settings, in response to a shock such as a pandemic. In addition to the eight original principles, we expanded to include two additional principles: (1) the need for functional structures and mechanisms for preparation and (2) adaptable governance and leadership structures to facilitate timely decision making and response coordination. We find the use of a people-centred approach also has value to prompt policy-makers to consider the acceptance of service adaptations by patients and health workers, and to continue the provision of 'routine services' for individuals during health systems shocks. CONCLUSION: Our study highlights the importance of a people-centred approach, placing the person at the centre of the health system, and value in applying and adapting the FCDO principles across diverse settings.

The majority of a collection of U.S. endocarditis Enterococcus faecalis isolates obtained from 1974 to 2004 lack capsular genes and belong to diverse, non-hospital-associated lineages.

Eighty-one endocarditis-derived Enterococcus faecalis isolates that were collected from individual patients in the United States between 1974 and 2004 were sequence typed and analyzed for the presence of various genes, including some previously associated with virulence. Overall, using our previously described trilocus sequence typing (TLST), 44 different sequence types (STs) were found within this collection; 26 isolates were singletons (a unique TLST sequence type [ST(T)]), some ST(T)s contained multiple isolates (up to 6 isolates), and 16% of the isolates (13 isolates) could be grouped by additional sequence typing into clonal cluster 21 (CC21). Of note, only four isolates (7%) of the 56 whose multilocus sequence types were determined were found to belong to one of the previously described hospital-associated clonal clusters CC2 and CC9, and only 15% and 37% of all isolates had high-level resistance to gentamicin and streptomycin, respectively, including 10% that were resistant to both. We also found that 64% of the isolates lacked the genes for production of capsule polysaccharide, which has been proposed to enhance the pathogenic potential of the hospital-associated clonal clusters. In summary, while our collection is not a random sample of cases of E. faecalis endocarditis, these results indicate that nonencapsulated strains belonging to non-hospital-associated lineages were predominant among endocarditis E. faecalis isolates recovered during this time period.

Complete genome sequence of Enterococcus faecium strain TX16 and comparative genomic analysis of Enterococcus faecium genomes.

BACKGROUND: Enterococci are among the leading causes of hospital-acquired infections in the United States and Europe, with Enterococcus faecalis and Enterococcus faecium being the two most common species isolated from enterococcal infections. In the last decade, the proportion of enterococcal infections caused by E. faecium has steadily increased compared to other Enterococcus species. Although the underlying mechanism for the gradual replacement of E. faecalis by E. faecium in the hospital environment is not yet understood, many studies using genotyping and phylogenetic analysis have shown the emergence of a globally dispersed polyclonal subcluster of E. faecium strains in clinical environments. Systematic study of the molecular epidemiology and pathogenesis of E. faecium has been hindered by the lack of closed, complete E. faecium genomes that can be used as references. RESULTS: In this study, we report the complete genome sequence of the E. faecium strain TX16, also known as DO, which belongs to multilocus sequence type (ST) 18, and was the first E. faecium strain ever sequenced. Whole genome comparison of the TX16 genome with 21 E. faecium draft genomes confirmed that most clinical, outbreak, and hospital-associated (HA) strains (including STs 16, 17, 18, and 78), in addition to strains of non-hospital origin, group in the same clade (referred to as the HA clade) and are evolutionally considerably more closely related to each other by phylogenetic and gene content similarity analyses than to isolates in the community-associated (CA) clade with approximately a 3-4% average nucleotide sequence difference between the two clades at the core genome level. Our study also revealed that many genomic loci in the TX16 genome are unique to the HA clade. 380 ORFs in TX16 are HA-clade specific and antibiotic resistance genes are enriched in HA-clade strains. Mobile elements such as IS16 and transposons were also found almost exclusively in HA strains, as previously reported. CONCLUSIONS: Our findings along with other studies show that HA clonal lineages harbor specific genetic elements as well as sequence differences in the core genome which may confer selection advantages over the more heterogeneous CA E. faecium isolates. Which of these differences are important for the success of specific E. faecium lineages in the hospital environment remain(s) to be determined.

Conservation of Ebp-type pilus genes among Enterococci and demonstration of their role in adherence of Enterococcus faecalis to human platelets.

Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species.

Dissemination of methicillin-resistant Staphylococcus aureus USA300 sequence type 8 lineage in Latin America.

BACKGROUND: Methicillin-resistant Staphylococus aureus (MRSA) is an important nosocomial and community-associated (CA) pathogen. Recently, a variant of the MRSA USA300 clone emerged and disseminated in South America, causing important clinical problems. METHODS: S. aureus isolates were prospectively collected (2006-2008) from 32 tertiary hospitals in Colombia, Ecuador, Peru, and Venezuela. MRSA isolates were subjected to antimicrobial susceptibility testing and pulsed-field gel electrophoresis and were categorized as health care-associated (HA)-like or CA-like clones on the basis of genotypic characteristics and detection of genes encoding Panton-Valentine leukocidin and staphylococcal cassette chromosome (SCC) mec IV. In addition, multilocus sequence typing of representative isolates of each major CA-MRSA pulsotype was performed, and the presence of USA300-associated toxins and the arcA gene was investigated for all isolates categorized as CA-MRSA. RESULTS: A total of 1570 S. aureus were included; 651 were MRSA (41%)--with the highest rate of MRSA isolation in Peru (62%) and the lowest in Venezuela (26%)--and 71%, 27%, and 2% were classified as HA-like, CA-like, and non-CA/HA-like clones, respectively. Only 9 MRSA isolates were confirmed to have reduced susceptibility to glycopeptides (glycopeptide-intermediate S. aureus phenotype). The most common pulsotype (designated ComA) among the CA-like MRSA strains was found in 96% of isolates, with the majority (81%) having a < or =6-band difference with the USA300-0114 strain. Representative isolates of this clone were sequence type 8; however, unlike the USA300-0114 strain, they harbored a different SCCmec IV subtype and lacked arcA (an indicator of the arginine catabolic mobile element). CONCLUSION: A variant CA-MRSA USA300 clone has become established in South America and, in some countries, is endemic in hospital settings.

A trilocus sequence typing scheme for hospital epidemiology and subspecies differentiation of an important nosocomial pathogen, Enterococcus faecalis.

In this study, we present a trilocus sequence typing (TLST) scheme based on intragenic regions of two antigenic genes, ace and salA (encoding a collagen/laminin adhesin and a cell wall-associated antigen, respectively), and a gene associated with antibiotic resistance, lsa (encoding a putative ABC transporter), for subspecies differentiation of Enterococcus faecalis. Each of the alleles was analyzed using 50 E. faecalis isolates representing 42 diverse multilocus sequence types (ST(M); based on seven housekeeping genes) and four groups of clonally linked (by pulsed-field gel electrophoresis [PFGE]) isolates. The allelic profiles and/or concatenated sequences of the three genes agreed with multilocus sequence typing (MLST) results for typing of 49 of the 50 isolates; in addition to the one exception, two isolates were found to have identical TLST types but were single-locus variants (differing by a single nucleotide) by MLST and were therefore also classified as clonally related by MLST. TLST was also comparable to PFGE for establishing short-term epidemiological relationships, typing all isolates classified as clonally related by PFGE with the same type. TLST was then applied to representative isolates (of each PFGE subtype and isolation year) of a collection of 48 hospital isolates and demonstrated the same relationships between isolates of an outbreak strain as those found by MLST and PFGE. In conclusion, the TLST scheme described here was shown to be successful for investigating short-term epidemiology in a hospital setting and may provide an alternative to MLST for discriminating isolates.

Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF.

BACKGROUND: Enterococcus faecalis has emerged as a major hospital pathogen. To explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly used for molecular manipulation and virulence studies. RESULTS: The 2,739,625 base pair chromosome of OG1RF was found to contain approximately 232 kilobases unique to this strain compared to V583, the only publicly available sequenced strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of divergence were classified into three categories. First, OG1RF carries 39 unique regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine replacements where a sequence specific to V583 was substituted by a sequence specific to OG1RF. For example, the iol operon of OG1RF replaces a possible prophage and the vanB transposon in V583. Finally, we found 16 regions that were present in V583 but missing from OG1RF, including the proposed pathogenicity island, several probable prophages, and the cpsCDEFGHIJK capsular polysaccharide operon. OG1RF was more rapidly but less frequently lethal than V583 in the mouse peritonitis model and considerably outcompeted V583 in a murine model of urinary tract infections. CONCLUSION: E. faecalis OG1RF carries a number of unique loci compared to V583, but the almost complete lack of mobile genetic elements demonstrates that this is not a defining feature of the species. Additionally, OG1RF's effects in experimental models suggest that mediators of virulence may be diverse between different E. faecalis strains and that virulence is not dependent on the presence of mobile genetic elements.