Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.

BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.

Experiences of capacity strengthening in sanitation and hygiene research in Africa and Asia: the SHARE Research Consortium.

The Sanitation and Hygiene Applied Research for Equity (SHARE) Research Programme consortium is a programme funded by the United Kingdom Department for International Development (DFID) that aims to contribute to achieving universal access to effective, sustainable, and equitable sanitation and hygiene worldwide. The capacity development component is an important pillar for this programme and different strategies were designed and implemented during the various phases of SHARE. This paper describes and reflects on the capacity-building strategies of this large multi-country research consortium, identifying lessons learnt and proposing recommendations for future global health research programmes. In the first phase, the strategy focused on increasing the capacity of individuals and institutions from low- and middle-income countries in conducting their own research. SHARE supported six PhD students and 25 MSc students, and organised a wide range of training events for different stakeholders. SHARE peer-reviewed all proposals that researchers submitted through several rounds of funding and offered external peer-review for all the reports produced under the partner's research platforms. In the second phase, the aim was to support capacity development of a smaller number of African research institutions to move towards their independent sustainability, with a stronger focus on early and mid-career scientists within these institutions. In each institution, a Research Fellow was supported and a specific capacity development plan was jointly developed.Strategies that yielded success were learning by doing (supporting institutions and postgraduate students on sanitation and hygiene research), providing fellowships to appoint mid-career scientists to support personal and institutional development, and supporting tailored capacity-building plans. The key lessons learnt were that research capacity-building programmes need to be driven by local initiatives tailored with support from partners. We recommend that future programmes seeking to strengthen research capacity should consider targeted strategies for individuals at early, middle and later career stages and should be sensitive to other institutional operations to support both the research and management capacities.

Evaluating the costs of cholera illness and cost-effectiveness of a single dose oral vaccination campaign in Lusaka, Zambia.

INTRODUCTION: In 2016, for the very first time, the Ministry of Health in Zambia implemented a reactive outbreak response to control the spread of cholera and vaccinated at-risk populations with a single dose of Shancol-an oral cholera vaccine (OCV). This study aimed to assess the costs of cholera illness and determine the cost-effectiveness of the 2016 vaccination campaign. METHODOLOGY: From April to June 2017, we conducted a retrospective cost and cost-effectiveness analysis in three peri-urban areas of Lusaka. To estimate costs of illness from a household perspective, a systematic random sample of 189 in-patients confirmed with V. cholera were identified from Cholera Treatment Centre registers and interviewed for out-of-pocket costs. Vaccine delivery and health systems costs were extracted from financial records at the District Health Office and health facilities. The cost of cholera treatment was derived by multiplying the subsidized cost of drugs by the quantity administered to patients during hospitalisation. The cost-effectiveness analysis measured incremental cost-effectiveness ratio-cost per case averted, cost per life saved and cost per DALY averted-for a single dose OCV. RESULTS: The mean cost per administered vaccine was US$1.72. Treatment costs per hospitalized episode were US$14.49-US$18.03 for patients ≤15 years old and US$17.66-US$35.16 for older patients. Whereas households incurred costs on non-medical items such as communication, beverages, food and transport during illness, a large proportion of medical costs were borne by the health system. Assuming vaccine effectiveness of 88.9% and 63%, a life expectancy of 62 years and Gross Domestic Product (GDP) per capita of US$1,500, the costs per case averted were estimated US$369-US$532. Costs per life year saved ranged from US$18,515-US$27,976. The total cost per DALY averted was estimated between US$698-US$1,006 for patients ≤15 years old and US$666-US$1,000 for older patients. CONCLUSION: Our study determined that reactive vaccination campaign with a single dose of Shancol for cholera control in densely populated areas of Lusaka was cost-effective.

Implementing large-scale health system strengthening interventions: experience from the better health outcomes through mentoring and assessments (BHOMA) project in Zambia.

BACKGROUND: Under the Doris Duke Charitable Foundation's African Health Initiative, five Population Health Implementation and Training partnerships were established as long-term health system strengthening projects in five Sub-Saharan Countries. In Zambia, the Centre for Infectious Disease Research in Zambia began to implement the Better Health Outcomes through Mentorship and Assessments (BHOMA) in 2009. This was a combined community and health systems project involving 42 public facilities and their catchment populations. The impact of this intervention is reported elsewhere, but less attention has been paid to evaluation approaches that generate an understanding of the forces shaping the intervention. This paper is focused on understanding the implementation practices of the BHOMA intervention in Zambia. METHODS: Qualitative approaches were employed to understand and explain health systems intervention implementation practices between 2014 and 2016. We purposively sampled six clinics out of the 42 that participated in the BHOMA project within three districts of Lusaka province in Zambia. At the facility-level we targeted health centre in-charges, health workers, and community health workers. In-depth interviews (n = 22), focus group discussions (n = 3) and observations were also collected and synthesised. RESULTS: The major health system challenges addressed by the BHOMA project included poor infrastructure, lack of human resources, poor service delivery, long distances to health centres and inadequate health information systems. In order to implement this in the districts it was necessary to engage with the Ministry of Health and district managers, however, these partners were not actively engaged in intervention design There was great variation in perceptions about the BHOMA interventions. The implementation team considered BHOMA as a 'proof of concept pilot project', running parallel to the public health system, while district health officials from the Ministry of health understood it as a 'long term partner' and were therefore resistant to the short-term nature of the intervention. CONCLUSIONS: The Normalization Process Theory provided a useful framework to understand and explain implementation processes for the BHOMA intervention in Zambia. We clearly demonstrated the applicability of all the four main components of the NPT: coherence (or sense-making); cognitive participation (or engagement); collective action and reflexive monitoring. We demonstrated how complex and dynamic the intervention played out among different actors and how implementation was affected by difference in appreciation and interpretation of the goal of the intervention. Our findings support the growing demand for process evaluations to use theory based approaches to examine how context interact with local interventions to affect outcomes intended or not. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01942278 . Registered: September 13, 2013 (Retrospectively registered).

Exploring community participation in project design: application of the community conversation approach to improve maternal and newborn health in Zambia.

BACKGROUND: The United Nations Development Programme (UNDP) has adopted an approach entitled Community Conversation (CC) to improve community engagement in addressing health challenges. CCs are based on Paulo Freire's transformative communication approach, in which communities pose problems and critically examine their everyday life experiences through discussion. We adopted this approach to engage communities in maternal and newborn health discussions in three rural districts of Zambia, with the aim of developing community-generated interventions. METHODS: Sixty (60) CCs were held in three target districts, covering a total of 20 health facilities. Communities were purposively selected in each district to capture a range of rural and peri-urban areas at varying distances from health facilities. Conversations were held four times in each community between May and September 2014. All conversations were digitally recorded and later transcribed. NVivo version 10 was used for data analysis. RESULTS AND DISCUSSION: The major barriers to accessing maternal health services included geography, limited infrastructure, lack of knowledge, shortage of human resources and essential commodities, and insufficient involvement of male partners. From the demand side, a lack of information and misconceptions, and, from the supply side, inadequately trained health workers with poor attitudes, negatively affected access to maternal health services in target districts either directly or indirectly. At least 17 of 20 communities suggested solutions to these challenges, including targeted community sensitisation on the importance of safe motherhood, family planning and prevention of teenage pregnancy. Community members and key stakeholders committed time and resources to address these challenges with minimal external support. CONCLUSION: We successfully applied the CC approach to explore maternal health challenges in three rural districts of Zambia. CCs functioned as an advocacy platform to facilitate direct engagement with key decision makers within the community and to align priorities while incorporating community views. There was a general lack of knowledge about safe motherhood and family planning in all three districts. However, other problems were unique to health facilities, demonstrating the need for tailored interventions.

Application of systems thinking: 12-month postintervention evaluation of a complex health system intervention in Zambia: the case of the BHOMA.

RATIONALE, AIMS AND OBJECTIVES: Strong health systems are said to be paramount to achieving effective and equitable health care. The World Health Organization has been advocating for using system-wide approaches such as 'systems thinking' to guide intervention design and evaluation. In this paper we report the system-wide effects of a complex health system intervention in Zambia known as Better Health Outcome through Mentorship and Assessment (BHOMA) that aimed to improve service quality. METHODS: We conducted a qualitative study in three target districts. We used a systems thinking conceptual framework to guide the analysis focusing on intended and unintended consequences of the intervention. NVivo version 10 was used for data analysis. RESULTS: The addressed community responded positively to the BHOMA intervention. The indications were that in the short term there was increased demand for services but the health worker capacity was not severely affected. This means that the prediction that service demand would increase with implementation of BHOMA was correct and the workload also increased, but the help of clinic lay supporters meant that some of the work of clinicians was transferred to these lay workers. However, from a systems perspective, unintended consequences also occurred during the implementation of the BHOMA. CONCLUSIONS: We applied an innovative approach to evaluate a complex intervention in low-income settings, exploring empirically how systems thinking can be applied in the context of health system strengthening. Although the intervention had some positive outcomes by employing system-wide approaches, we also noted unintended consequences.

Research capacity building integrated into PHIT projects: leveraging research and research funding to build national capacity.

BACKGROUND: Inadequate research capacity impedes the development of evidence-based health programming in sub-Saharan Africa. However, funding for research capacity building (RCB) is often insufficient and restricted, limiting institutions' ability to address current RCB needs. The Doris Duke Charitable Foundation's African Health Initiative (AHI) funded Population Health Implementation and Training (PHIT) partnership projects in five African countries (Ghana, Mozambique, Rwanda, Tanzania and Zambia) to implement health systems strengthening initiatives inclusive of RCB. METHODS: Using Cooke's framework for RCB, RCB activity leaders from each country reported on RCB priorities, activities, program metrics, ongoing challenges and solutions. These were synthesized by the authorship team, identifying common challenges and lessons learned. RESULTS: For most countries, each of the RCB domains from Cooke's framework was a high priority. In about half of the countries, domain specific activities happened prior to PHIT. During PHIT, specific RCB activities varied across countries. However, all five countries used AHI funding to improve research administrative support and infrastructure, implement research trainings and support mentorship activities and research dissemination. While outcomes data were not systematically collected, countries reported holding 54 research trainings, forming 56 mentor-mentee relationships, training 201 individuals and awarding 22 PhD and Masters-level scholarships. Over the 5 years, 116 manuscripts were developed. Of the 59 manuscripts published in peer-reviewed journals, 29 had national first authors and 18 had national senior authors. Trainees participated in 99 conferences and projects held 37 forums with policy makers to facilitate research translation into policy. CONCLUSION: All five PHIT projects strongly reported an increase in RCB activities and commended the Doris Duke Charitable Foundation for prioritizing RCB, funding RCB at adequate levels and time frames and for allowing flexibility in funding so that each project could implement activities according to their trainees' needs. As a result, many common challenges for RCB, such as adequate resources and local and international institutional support, were not identified as major challenges for these projects. Overall recommendations are for funders to provide adequate and flexible funding for RCB activities and for institutions to offer a spectrum of RCB activities to enable continued growth, provide adequate mentorship for trainees and systematically monitor RCB activities.

Costs of introducing pneumococcal, rotavirus and a second dose of measles vaccine into the Zambian immunisation programme: Are expansions sustainable?

BACKGROUND: Introduction of new vaccines in low- and lower middle-income countries has accelerated since Gavi, the Vaccine Alliance was established in 2000. This study sought to (i) estimate the costs of introducing pneumococcal conjugate vaccine, rotavirus vaccine and a second dose of measles vaccine in Zambia; and (ii) assess affordability of the new vaccines in relation to Gavi's co-financing and eligibility policies. METHODS: Data on 'one-time' costs of cold storage expansions, training and social mobilisation were collected from the government and development partners. A detailed economic cost study of routine immunisation based on a representative sample of 51 health facilities provided information on labour and vaccine transport costs. Gavi co-financing payments and immunisation programme costs were projected until 2022 when Zambia is expected to transition from Gavi support. The ability of Zambia to self-finance both new and traditional vaccines was assessed by comparing these with projected government health expenditures. RESULTS: 'One-time' costs of introducing the three vaccines amounted to US$ 0.28 per capita. The new vaccines increased annual immunisation programme costs by 38%, resulting in economic cost per fully immunised child of US$ 102. Co-financing payments on average increased by 10% during 2008-2017, but must increase 49% annually between 2017 and 2022. In 2014, the government spent approximately 6% of its health expenditures on immunisation. Assuming no real budget increases, immunisation would account for around 10% in 2022. Vaccines represented 1% of government, non-personnel expenditures for health in 2014, and would be 6% in 2022, assuming no real budget increases. CONCLUSION: While the introduction of new vaccines is justified by expected positive health impacts, long-term affordability will be challenging in light of the current economic climate in Zambia. The government needs to both allocate more resources to the health sector and seek efficiency gains within service provision.

A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.

BACKGROUND: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease.

Premature adult mortality in urban Zambia: a repeated population-based cross-sectional study.

OBJECTIVES: To measure the sex-specific and community-specific mortality rates for adults in Lusaka, Zambia, and to identify potential individual-level, household-level and community-level correlates of premature mortality. We conducted 12 survey rounds of a population-based cross-sectional study between 2004 and 2011, and collected data via a structured interview with a household head. SETTING: Households in Lusaka District, Zambia, 2004-2011. PARTICIPANTS: 43,064 household heads (88% female) who enumerated 123,807 adult household members aged between 15 and 60 years. PRIMARY OUTCOME: Premature adult mortality. RESULTS: The overall mortality rate was 16.2/1000 person-years for men and 12.3/1000 person-years for women. The conditional probability of dying between age 15 and 60 (45q15) was 0.626 for men and 0.537 for women. The top three causes of death for men and women were infectious in origin (ie, tuberculosis, HIV and malaria). We observed an over twofold variation of mortality rates between communities. The mortality rate was 1.98 times higher (95% CI 1.57 to 2.51) in households where a family member required nursing care, 1.44 times higher (95% CI 1.22 to 1.71) during the cool dry season, and 1.28 times higher (95% CI 1.06 to 1.54) in communities with low-cost housing. CONCLUSIONS: To meet Zambia's development goals, further investigation is needed into the factors associated with adult mortality. Mortality can potentially be reduced through focus on high-need households and communities, and improved infectious disease prevention and treatment services.

Health Promotion Through Existing Community Structures: A Case of Churches' Roles in Promoting Rotavirus Vaccination in Rural Zambia.

INTRODUCTION: Rural populations, particularly in Africa, suffer worse health outcomes from poor health services access. Community health workers (CHWs) effectively improve health outcomes, but the best means for CHWs reaching rural populations is unknown. Since Zambia is predominantly Christian, this study explored the use of CHWs through churches as an existing community structure for promoting preventive health behaviors, specifically rotavirus vaccine uptake. METHODS: A noncontrolled cross-sectional study of 32 churches receiving a packaged intervention of diarrhea prevention and treatment messaging was conducted with repeated time points of data collection over 13 months (2013-2014) in the Kafue District of Zambia. Two churches were selected for each of the 17 catchment areas, and CHWs were identified and trained in the intervention of promoting 4 key messages related to diarrhea prevention and treatment: hand washing with soap, exclusive breast-feeding, rotavirus vaccination, and treating diarrhea with oral rehydration solution and zinc. The intervention was conducted within existing church's women's groups, and data was collected on attendance and the distribution of Rota Cards for tracking rotavirus immunizations. RESULTS: Nineteen (59%) churches completed the study, and CHWs delivered health messages at a total of 890 women's group meetings. The overall reach of the intervention was to 37.0% of church-attending women, and the efficacy was 67.7% (317 of 468 Rota Cards collected at health centers). DISCUSSION: Implementing community health programs is often expensive and unsustainable, but the reach and efficacy levels achieved through existing structures like churches are encouraging in resource-constrained countries. Churches can be effective channels for delivering health prevention strategies to often difficult-to-reach rural populations. Further research is needed to investigate the impact of the intervention on health outcomes.

Managing multiple funding streams and agendas to achieve local and global health and research objectives: lessons from the field.

Multiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia.

Protocol-driven primary care and community linkages to improve population health in rural Zambia: the Better Health Outcomes through Mentoring and Assessment (BHOMA) project.

INTRODUCTION: Zambia's under-resourced public health system will not be able to deliver on its health-related Millennium Development Goals without a substantial acceleration in mortality reduction. Reducing mortality will depend not only upon increasing access to health care but also upon improving the quality of care that is delivered. Our project proposes to improve the quality of clinical care and to improve utilization of that care, through a targeted quality improvement (QI) intervention delivered at the facility and community level. DESCRIPTION OF IMPLEMENTATION: The project is being carried out 42 primary health care facilities that serve a largely rural population of more than 450,000 in Zambia's Lusaka Province. We have deployed six QI teams to implement consensus clinical protocols, forms, and systems at each site. The QI teams define new clinical quality expectations and provide tools needed to deliver on those expectations. They also monitor the care that is provided and mentor facility staff to improve care quality. We also engage community health workers to actively refer and follow up patients. EVALUATION DESIGN: Project implementation occurs over a period of four years in a stepped expansion to six randomly selected new facilities every three months. Three annual household surveys will determine population estimates of age-standardized mortality and under-5 mortality in each community before, during, and after implementation. Surveys will also provide measures of childhood vaccine coverage, pregnancy care utilization, and general adult health. Health facility surveys will assess coverage of primary health interventions and measures of health system effectiveness. DISCUSSION: The patient-provider interaction is an important interface where the community and the health system meet. Our project aims to reduce population mortality by substantially improving this interaction. Our success will hinge upon the ability of mentoring and continuous QI to improve clinical service delivery. It will also be critical that once the quality of services improves, increasing proportions of the population will recognize their value and begin to utilize them.

Engaging diverse communities participating in clinical trials: case examples from across Africa.

BACKGROUND: In the advent of increasing international collaborative research involving participants drawn from populations with diverse cultural backgrounds, community engagement becomes very critical for the smooth conduction of the research. The African Malaria Network Trust (AMANET) is a pan-African non-governmental organization that sponsors and technically supports malaria vaccine trials in various African countries. CASE DESCRIPTION: AMANET sponsored phase Ib or IIb clinical trials of several malaria vaccine candidates in various Africa countries. In Burkina Faso, Mali and Tanzania trials of the merozoite surface protein 3 -- in its Long Synthetic Peptide configuration (MSP3 LSP) -- were conducted. In Mali, the apical membrane antigen 1 (AMA1) was tested, while a hybrid of glutamate rich protein (GLURP) and MSP3 (GMZ2) was tested in Gabon. AMANET recognizes the importance of engaging with the communities from which trial participants are drawn, hence community engagement was given priority in all project activities conducted in the various countries. DISCUSSION AND EVALUATION: Existing local social systems were used to engage the communities from which clinical trial participants were drawn. This article focuses on community engagement activities employed at various AMANET-supported clinical trial sites in different countries, highlighting subtle differences in the approaches used. The paper also gives some general pros and cons of community engagement. CONCLUSIONS: Community engagement enables two-way sharing of accurate information and ideas between researchers and researched communities, which helps to create an environment conducive to smooth research activities with enhanced sense of research ownership by the communities.

Capacity building of ethics review committees across Africa based on the results of a comprehensive needs assessment survey.

A needs assessment survey of ethics review committees (ERCs) across Africa was conducted in order to establish their major needs and areas of weaknesses in terms of ethical review capacity. The response rate was 84% (31 of 37 targeted committees), and committees surveyed were located in 18 African countries. The majority of the responding committees (61%) have been in existence between 5 and 10 years; approximately 74% of the respondents were institutional committees, with the remainder being either national (6/31) or regional (2/31). In terms of the ethical review process, nine of the 31 committees that responded did not have standard operating procedures (SOPs), and seven of the 22 that did have SOPs had never revised them after their initial development (an average period of three years). Of the 31 committees, 10 operated without any ethical guidelines. Many of the committees (13/30) met once per month, and the number of proposals reviewed annually varied, ranging from five to over 100. All respondents relied on paper-based data management and archiving systems. Overall, the survey identified the major constraints on ERCs as lack of office equipment, outdated or lack of SOPs, lack of electronic data management systems, inadequate resources, lack of or insufficient expertise on the committees, and poor recognition of the importance of the role of the committees. Consequently, the authors are addressing the identified needs and weaknesses through the Bill and Melinda Gates Foundation-funded capacity building project. The impact of the intervention project will be assessed during and at the end of the four-year longitudinal project.

An ethics perspective on responsibilities of investigators, sponsors and research participants.

The major international guidelines for health research have come a long way in setting standards and providing direction on acceptable practices for the conduct of research. However, the responsibilities of the key players have generally been addressed in a rather uncoordinated manner, and there still remain gaps in addressing the responsibilities of some of the key players in the research setting. This paper is a review of crosscutting guidelines and mix of the key responsibilities of investigators, sponsors, study participants together with their communities. Some new responsibilities for the participants and research institutions have be suggested based on understanding and practical experience as they are not described in any traditional literature.