Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.

An assessment of excess mortality during the COVID-19 pandemic, a retrospective post-mortem surveillance in 12 districts - Zambia, 2020-2022.

BACKGROUND: The number of COVID-19 deaths reported in Zambia (N = 4069) is most likely an underestimate due to limited testing, incomplete death registration and inability to account for indirect deaths due to socioeconomic disruption during the pandemic. We sought to assess excess mortality during the COVID-19 pandemic in Zambia. METHODS: We conducted a retrospective analysis of monthly-death-counts (2017-2022) and individual-daily-deaths (2020-2022) of all reported health facility and community deaths at district referral health facility mortuaries in 12 districts in Zambia. We defined COVID-19 wave periods based on a sustained nationally reported SARS-CoV-2 test positivity of greater than 5%. Excess mortality was calculated as the difference between observed monthly death counts during the pandemic (2020-2022) and the median monthly death counts from the pre-pandemic period (2017-2019), which served as the expected number of deaths. This calculation was conducted using a Microsoft Excel-based tool. We compared median daily death counts, median age at death, and the proportion of deaths by place of death (health facility vs. community) by wave period using the Mann-Whitney-U test and chi-square test respectively in R. RESULTS: A total of 112,768 deaths were reported in the 12 districts between 2020 and 2022, of which 17,111 (15.2%) were excess. Wave periods had higher median daily death counts than non-wave periods (median [IQR], 107 [95-126] versus 96 [85-107], p < 0.001). The median age at death during wave periods was older than non-wave periods (44.0 [25.0-67.0] versus 41.0 [22.0-63.0] years, p < 0.001). Approximately half of all reported deaths occurred in the community, with an even greater proportion during wave periods (50.6% versus 53.1%, p < 0.001), respectively. CONCLUSION: There was excess mortality during the COVID-19 pandemic in Zambia, with more deaths occurring within the community during wave periods. This analysis suggests more COVID-19 deaths likely occurred in Zambia than suggested by officially reported numbers. Mortality surveillance can provide important information to monitor population health and inform public health programming during pandemics.

Detection and Characterisation of SARS-CoV-2 in Eastern Province of Zambia: A Retrospective Genomic Surveillance Study.

Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity and vaccine escape among others. Genome sequencing is a technique that allows scientists to read the genetic code of an organism and has become a powerful tool for studying emerging infectious diseases. Here, we conducted a cross-sectional study in selected districts of the Eastern Province of Zambia, from November 2021 to February 2022. We analyzed SARS-CoV-2 samples (n = 76) using high-throughput sequencing. A total of 4097 mutations were identified in 69 SARS-CoV-2 genomes with 47% (1925/4097) of the mutations occurring in the spike protein. We identified 83 unique amino acid mutations in the spike protein of the seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 and XT). Of these, 43.4% (36/83) were present in the receptor binding domain, while 14.5% (12/83) were in the receptor binding motif. While we identified a potential recombinant XT strain, the highly transmissible BA.2 sublineage was more predominant (40.8%). We observed the substitution of other variants with the Omicron strain in the Eastern Province. This work shows the importance of pandemic preparedness and the need to monitor disease in the general population.

Wastewater Surveillance of SARS-CoV-2 in Zambia: An Early Warning Tool.

Wastewater-based surveillance has emerged as an important method for monitoring the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time Polymerase Chain Reaction (PCR). Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and 2 sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.

BACKGROUND: Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. METHODS AND FINDINGS: In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. CONCLUSION: In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.

Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.

The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.

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.

Persistent Immune Activation in Human Immunodeficiency Virus-Infected Pregnant Women Starting Combination Antiretroviral Therapy After Conception.

This study evaluated the impact of human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV-exposed but uninfected children followed up from birth. Activated CD8+ T cells (CD38+ and HLA-DR+) were compared among HIV-uninfected (n = 95), cART experienced HIV-infected (n = 111), and cART-naive HIV-infected (n = 21) pregnant women. Immune activation was highest among HIV-infected/cART-naive women but decreased during pregnancy. Immune activation HIV-infected women who started cART during pregnancy was reduced but not to levels similar to those in HIV-uninfected women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.

Leveraging HIV Program and Civil Society to Accelerate COVID-19 Vaccine Uptake, Zambia.

To accelerate COVID-19 vaccination delivery, Zambia integrated COVID-19 vaccination into HIV treatment centers and used World AIDS Day 2021 to launch a national vaccination campaign. This campaign was associated with significantly increased vaccinations, demonstrating that HIV programs can be leveraged to increase COVID-19 vaccine uptake.

Contrasting Epidemiology of Cholera in Bangladesh and Africa.

In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera's elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of cholera's epidemiology in African countries which appear different from the Ganges Delta.

Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.

BACKGROUND: Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. RESULTS: Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years. CONCLUSIONS: Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.

High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia.

Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.

"It depends how one understands it:" a qualitative study on differential uptake of oral cholera vaccine in three compounds in Lusaka, Zambia.

BACKGROUND: The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December. Understanding uptake of this first-ever two-dose OCV campaign is critical to design effective OCV campaigns and for delivery of oral vaccines in the country and the region. METHODS: We conducted 12 Focus Group Discussions (FGDs) with men and women who self-reported taking no OCV doses and six with those self-reporting taking both doses. Simple descriptive analysis was conducted on socio-demographic and cholera-related data collected using a short questionnaire. We analyzed transcribed FGDs using the framework of dose, gender and geographic location. RESULTS: No differences were found by gender and location. All participants thought cholera to be severe and the reactive OCV campaign as relevant if efficacious. Most reported not receiving information on OCV side-effects and duration of protection. Those who took both doses listed more risk factors (including 'wind') and felt personally susceptible to cholera and protected by OCV. Some described OCV side-effects, mostly diarrhoea, vomiting and dizziness, as the expulsion of causative agents. Those who did not take OCV felt protected by their good personal hygiene practices or, thought of themselves and OCV as powerless against the multiple causes of cholera including poor living conditions, water, wind, and curse. Most of those who did not take OCV feared side-effects reported by others. Some interpreted side-effects as 'western' malevolence. Though > 80% discussants reported not knowing duration of protection, some who did not vaccinate, suggested that rather than rely on OCV which could lose potency, collective action should be taken to change the physical and economic environment to prevent cholera. CONCLUSIONS: Due to incomplete information, individual decision-making was complex, rooted in theories of disease causation, perceived susceptibility, circulating narratives, colonial past, and observable outcomes of vaccination. To increase coverage, future OCV campaigns may benefit from better communication on eligibility and susceptibility, expected side effects, mechanism of action, and duration of protection. Governmental improvements in the physical and economic environment may increase confidence in OCV and other public health interventions among residents in Lusaka compounds.

Using a theory-driven creative process to design a peri-urban on-site sanitation quality improvement intervention.

BACKGROUND: Behavior change interventions have been developed by drawing from many different theories using design processes of varying specificity. We describe the development of a behavior change intervention to improve on-site peri-urban sanitation quality in Lusaka, Zambia using the Behavior Centered Design (BCD) framework to explain the results of the process applied to improving the quality of shared peri-urban sanitation and compare them to similar interventions. METHODS: We used the BCD behavioral determinants model to synthesize the data from our literature review and formative research. Then, we partnered with creative professionals using a design process to develop a theory-driven on-site peri-urban sanitation intervention. Particular attention was paid to the implications of using BCD for intervention development on improving its effectiveness, increasing the contributions to knowledge for other behaviors and settings, and advancing the discipline of applied behavioral science. RESULTS: Based on findings from a literature review and formative research, we designed an intervention to encourage landlords to improve their toilets by making them more accessible, desirable, hygienic, and sustainable. The intervention involved landlords meeting in facilitated groups every 2 weeks with individual follow-up after each meeting. The meetings presented surprising "hidden camera"-style videos to reveal tenants' perspectives, used participatory activities to help landlords reevaluate the benefits they would derive from improving sanitation on their plots, and provided practical guidance and mechanisms to facilitate the performance of construction and cleaning behaviors. CONCLUSIONS: Using the BCD framework provided an easy-to-follow intervention design process. The resulting intervention is highly creative and multi-faceted, with each element having a theoretical role in an explicit theory of change. The development of this theory-driven intervention advances applied behavioral science by facilitating evaluation of each of the behavior change techniques and the overall delivery mechanism hypothesized to change the target behaviors. This informs the adaptation of these findings to improving on-site sanitation in other settings and the iterative development of the BCD model, which can be used to more effectively change other behaviors.

Early linear growth retardation: results of a prospective study of Zambian infants.

BACKGROUND: Linear growth retardation is the most dominant nutritional problem globally. We aimed to describe linear growth trajectory among infants under 2 years of age using the WHO growth velocity standards. METHOD: This was a prospective cohort study of infants enrolled at 6 weeks of age and followed up for up to 24 months in Kamwala Urban Health Centre, Lusaka, Zambia. The study was conducted between April 2013 and March 2015. Infants were enrolled if they were 6-12 weeks of age and the mother was willing to participate voluntarily and provided informed consent. Anthropometric data were collected at scheduled clinic visits at 1 month, 2 months, 3 months, then quarterly until the infant was 24 months old. We defined linear growth velocity as the rate of change in height. We estimated linear growth velocity as the first derivative of the penalized cubic spline mixed effects model. RESULTS: A total of 338 children were included in the analysis. Of these, 185 (54.7%) were female, 115 (34.1%) were born to HIV positive mothers and thus classified as HIV Exposed (HE). The mean age of children at enrollment was 1.6 months (SD = 0.15). On average, the growth velocity for 3-month length increments conditional on age were 0-3 months = 2.97 cm/3mo (95%CI = 2.69, 3.25); 3-6 months = 2.62 cm/3mo (95%CI = 2.38, 2.87); 6-9 months = 1.57 cm/3mo (95%CI = 1.43, 1.71); 9-12 months = 1.18 cm/3mo (95%CI = 1.08, 1.28); 12-15 month = 1.14 cm/3mo (95%CI = 1.02, 1.27); 15-18 months = 0.87 cm/3mo (95%CI = 0.79, 0.96); 18-21 months = 0.80 cm/3mo (95%CI = 0.72, 0.89); and 21-24 months = 0.86 cm/3mo (95%CI = 0.77, 0.96). For both boys and girls, the growth velocity in our cohort were consistently below the 3rd percentile of the WHO linear growth velocity standard. The estimated mean height and the age at which growth begins to falter were 68.6 cm (95%CI = 68.0, 69.2) and 13.6 months (95%CI = 13.2, 14.1) respectively. CONCLUSION: We found slower rate of growth among otherwise healthy Zambian infants. The data suggests that growth retardation is universal and profound in this cohort and may have already been occurring in utero.

Menstrual hygiene management in rural schools of Zambia: a descriptive study of knowledge, experiences and challenges faced by schoolgirls.

INTRODUCTION: While in school, girls require an environment that is supportive of menstrual hygiene management (MHM) in order to ensure regular school attendance and participation. Little is known about schoolgirls access to and practice of MHM in rural Zambia. This study explores girls' experiences of MHM in rural schools of Zambia from the perspectives of schoolgirls, schoolboys and community and school-based adults key to MHM for schoolgirls. METHODS: In July and August 2015, we conducted this qualitative exploratory study in six rural schools of Mumbwa and Rufunsa districts of Zambia. Twelve in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among girls ages 14-18 who had begun menstruating. Two FGDs with boys ages 14-18 and 25 key informant interviews were also conducted with teachers, female guardians and traditional leaders to provide the context within which schoolgirls practice MHM. RESULTS: Most girls reported learning about menstruation only at menarche and did not know the physiological basis of menstruation. They reported MHM-related challenges, including: use of non-absorbent and uncomfortable menstrual cloth and inadequate provision of sanitary materials, water, hygiene and sanitation facilities (WASH) in schools. In particular, toilets did not have soap and water or doors and locks for privacy and had a bad odor. Girls' school attendance and participation in physical activities was compromised when menstruating due to fear of teasing (especially by boys) and embarrassment from menstrual leakage. Boys said they could tell when girls were menstruating by the smell and their behaviour, for instance, moving less and isolating themselves from their peers. Girls complained of friction burns on their inner thighs during their long journey to school due to chaffing of wet non-absorbent material used to make menstrual cloth. Girls preferred to dispose used menstrual materials in pit latrines and not waste bins for fear that they could be retrieved for witchcraft against them. Though traditional leaders and female guardians played a pivotal role in teaching girls MHM, they have not resolved challenges to MHM among schoolgirls. CONCLUSION: When menstruating, schoolgirls in rural Zambia would rather stay home than be uncomfortable, inactive and embarrassed due to inadequate MHM facilities at school. A friendly and supportive MHM environment that provides education, absorbent sanitary materials and adequate WASH facilities is essential to providing equal opportunity for all girls.

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.

Theory-driven formative research on on-site, shared sanitation quality improvement among landlords and tenants in peri-urban Lusaka, Zambia.

Rapid, unplanned urbanization in low-income countries is leading to increasing problems of dealing with human waste. On-site sanitation systems are often rudimentary, unhygienic, and poorly maintained. In-depth, on-site interactive interviews were conducted with 33 landlords and 33 tenants in a neighborhood in peri-urban Lusaka to understand on-site, shared sanitation quality improvement behaviors and preferences. Respondents were asked about housing characteristics, toilet histories, and financial decision-making. Improved, shared toilets were common (79%), but many were of low quality and poorly cleaned. Poor coordination among tenants, barriers to communication between landlords and tenants, and landlords viewing sanitation as a required basic service to provide instead of something for which tenants will pay more rent all limit the quality of sanitation in this setting. Landlord-directed interventions targeting non-health motivations for sanitation improvement and introducing effective cleaning systems may increase peri-urban sanitation quality.

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).

Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia.

BACKGROUND: We investigated changes in hepatic fibrosis, based on transient elastography (TE), among human immunodeficiency virus (HIV)-infected patients with and without hepatitis B virus (HBV) coinfection on antiretroviral therapy (ART) in Zambia. METHODS: Patients' liver stiffness measurements (LSM; kiloPascals [kPa]) at ART initiation were categorized as no or minimal fibrosis (equivalent to Metavir F0-F1), significant fibrosis (F2-F3), and cirrhosis (F4). TE was repeated following 1 year of ART. Stratified by HBV coinfection status (hepatitis B surface antigen positive at baseline), we described LSM change and the proportion with an increase/decrease in fibrosis category. Using multivariable logistic regression, we assessed correlates of significant fibrosis/cirrhosis at 1 year on ART. RESULTS: Among 463 patients analyzed (61 with HBV coinfection), median age was 35 years, 53.7% were women, and median baseline CD4+ count was 240 cells/mm3. Nearly all (97.6%) patients received tenofovir disoproxil fumarate-containing ART, in line with nationally recommended first-line treatment. The median LSM change was -0.70 kPa (95% confidence interval, -3.0 to +1.7) and was similar with and without HBV coinfection. Significant fibrosis/cirrhosis decreased in frequency from 14.0% to 6.7% (P < .001). Increased age, male sex, and HBV coinfection predicted significant fibrosis/cirrhosis at 1 year (all P < .05). CONCLUSION: The percentage of HIV-infected Zambian adults with elevated liver stiffness suggestive of significant fibrosis/cirrhosis decreased following ART initiation-regardless of HBV status. This suggests that HIV infection plays a role in liver inflammation. HBV-coinfected patients were more likely to have significant fibrosis/cirrhosis at 1 year on ART. CLINICAL TRIALS REGISTRATION: NCT02060162.