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Background: Vaccination is an important public health intervention, but not everyone benefits equally. Biological, social and structural factors render some communities vulnerable and unable to secure optimal health benefits from vaccination programmes. This drives health inequity and undermines wider vaccine impact by allowing the persistence of non-immune communities as foci for recurrent disease outbreaks. The NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard) aims to understand how biological, social, and structural factors interact to impair vaccine impact in vulnerable African communities. Methods: The VAnguard project will be implemented through three thematic work packages (1-3) and four cross-cutting work packages (4-7). Work package 1 will investigate the biological drivers and mechanisms of population differences in vaccine responses. Work package 2 will support the understanding of how structural, social and biological determinants of vaccine response interrelate to determine vaccine impact. Work package 3 will synthesise data and lead analyses to develop, model and test community-based integrated strategies to optimise vaccine access, uptake and effectiveness. Work package 4 will plan and implement field investigations (community survey and qualitative studies (with support of work package 2) to explore structural, social & biological determinants impairing vaccine impact. Work package 5 will collaborate with work packages 1-4, to engage communities in designing interventions that aim to directly optimise vaccine impact through a process of co-learning and co-creation between them and the researchers. Work package 6 will build capacity for, and a culture of, consultative, collaborative multidisciplinary vaccine research in East Africa. Work package 7 will support the overall project management and governance. Following the project inception on the 1 st of September 2022, project launch was held in November 2022. Conclusion: Results from this project will contribute to the development of integrated strategies that will optimise vaccine benefits and drive health equity.
Vaccination is an important public health intervention but not everyone benefits equally. Some vaccines give weaker protection in people from rural, tropical settings than in those from high income settings. Some new vaccines, under development, also elicit weaker responses in people living in low-income, rural settings. The biological reasons for this are not fully understood. Also, some people benefit less from vaccines for socioeconomic reasons, such as the social context of the communities they live in, including limited access to accurate information to aid vaccine choices. Social and biological factors can interact to make communities "vulnerable" in terms of vaccine impact. This needs to be addressed to promote health equity, but also to secure maximum global benefit from vaccines. VAnguard's goal is to understand how biological, social, and structural factors interact to impair vaccine impact in vulnerable African communities, and to develop integrated strategies to optimise vaccine benefits and drive health equity. First, we shall work with national stakeholders (such as Ministries of Health, and vaccine-related non-governmental organisations), review literature, and work on samples from previous studies, to identify Ugandan and Kenyan communities likely to have the most difficulty in getting the best out of vaccination programmes ("vulnerable communities"). Then, with stakeholders and communities, we shall co-design the VAnguard Community Study, and implement it to investigate in detail which biological and social factors most influence vaccine impact in vulnerable communities. Data and economic modellers will study the results to identify which factors could usefully be modified, and we shall work with the communities to explore ways in which this could be done. Hence, we shall co-develop strategies which national stakeholders may be able to implement straight away, or which can be tested in future studies.
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Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta-analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04-1.07 and I2 = 93.5%) for direct helminth exposure and 0.01 (95% CI -0.04 to 0.07 and I2 = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth-associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.
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Anti-Helmínticos , Helmintíase , Helmintos , Vacinas , Animais , Anti-Helmínticos/uso terapêutico , Feminino , Humanos , Gravidez , VacinaçãoRESUMO
INTRODUCTION: Drivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on Plasmodium falciparum malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses. METHODS AND ANALYSIS: We have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day 'zero'; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: Current Controlled Trials identifier: ISRCTN62041885.
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Antimaláricos , Malária , Adolescente , Antimaláricos/uso terapêutico , Artemisininas , Combinação de Medicamentos , Humanos , Imunidade , Malária/tratamento farmacológico , Malária/prevenção & controle , Quinolinas , Ensaios Clínicos Controlados Aleatórios como Assunto , UgandaRESUMO
INTRODUCTION: There is evidence that BCG immunisation may protect against unrelated infectious illnesses. This has led to the postulation that administering BCG before unrelated vaccines may enhance responses to these vaccines. This might also model effects of BCG on unrelated infections. METHODS AND ANALYSIS: To test this hypothesis, we have designed a randomised controlled trial of BCG versus no BCG immunisation to determine the effect of BCG on subsequent unrelated vaccines, among 300 adolescents (aged 13-17 years) from a Ugandan birth cohort. Our schedule will comprise three main immunisation days (week 0, week 4 and week 28): BCG (or no BCG) revaccination at week 0; yellow fever (YF-17D), oral typhoid (Ty21a) and human papillomavirus (HPV) prime at week 4; and HPV boost and tetanus/diphtheria (Td) boost at week 28. Primary outcomes are anti-YF-17D neutralising antibody titres, Salmonella typhi lipopolysaccharide-specific IgG concentration, IgG specific for L1-proteins of HPV-16/HPV-18 and tetanus and diphtheria toxoid-specific IgG concentration, all assessed at 4 weeks after immunisation with YF, Ty21a, HPV and Td, respectively. Secondary analyses will determine effects on correlates of protective immunity (where recognised correlates exist), on vaccine response waning and on whether there are differential effects on priming versus boosting immunisations. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of BCG revaccination on vaccine responses. Further analyses will assess which life course exposures influence vaccine responses in adolescence. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: ISRCTN10482904.
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Vacina BCG , Tétano , Adolescente , Humanos , Imunização Secundária , Ensaios Clínicos Controlados Aleatórios como Assunto , Uganda , VacinaçãoRESUMO
INTRODUCTION: Vaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering identification of strategies for optimising vaccine effectiveness. We hypothesise that urban-rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections. METHODS AND ANALYSIS: Three related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day '0'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and 'trans-kingdom' mediators in parasite modulation of vaccine-specific responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBERS: ISRCTN60517191, ISRCTN62041885, ISRCTN10482904.
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Vacina BCG , Vacinação , Adolescente , Humanos , Imunidade , Imunização Secundária , Ensaios Clínicos Controlados Aleatórios como Assunto , UgandaRESUMO
INTRODUCTION: Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response. METHODS AND ANALYSIS: We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9-17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day 'zero'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: ISRCTN60517191.
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Esquistossomose , Adolescente , Animais , Humanos , Imunidade , Ilhas , Praziquantel , Ensaios Clínicos Controlados Aleatórios como Assunto , UgandaRESUMO
The 3rd Uganda Conference on Cancer and Palliative Care was held in September 2021 with the theme: cancer and palliative care in COVID-19 and other challenging situations. It was hosted by the Uganda Cancer Institute and the Palliative Care Association of Uganda (UCI-PCAU). The conference was held virtually, with a mix of pre-recorded sessions, plenary sessions being broadcast live on television (TV) by the Uganda Broadcasting Corporation TV, live speakers at the studio and others presenting in real time via Zoom. The conference brought together >350 participants who participated on Zoom, along with those attending in person at the studio and those watching the plenary sessions on TV. At the heart of this joint UCI-PCAU conference was the commitment to not only continue but to improve the provision of cancer care and palliative care within Uganda. Key themes from the conference included: the importance of Universal Health Coverage; the impact of COVID-19 on the provision of cancer and palliative care; that both cancer care and palliative care are available in Uganda; education for all; the importance of working together to provide care and overcome challenges, e.g. through technology; the resilience shown by those working in cancer and palliative care; the grief experienced by so many people who have lost loved ones during the pandemic; the importance of good health seeking behaviour - prevention is better than cure; the challenge of funding; the need for health care equity for marginalised and vulnerable populations and finally we can't wait for the world to stop COVID-19 - COVID-19 is here to stay - we need to find solutions. The last few years have seen significant challenges due to the COVID-19 pandemic; however, despite this, cancer and palliative care service provision has continued. This conference, whilst unique and very different from previous conferences, was a great opportunity to share not only amongst each other, but also to share key messages with the public through the live broadcasting of the plenary sessions of the conference.
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CONTEXT: Mobile health (mHealth) provides an opportunity to use internet coverage in low- and middle-income countries to improve palliative care access and quality. OBJECTIVES: This study aimed to design a mobile phone application (app) to enable or improve communication between family caregivers, community caregivers, and palliative care teams; to evaluate its acceptability, processes, and mechanisms of action; and to propose refinements. METHODS: A codesign process entailed collaboration between a Project Advisory Group and collaborators in India, Uganda, and Zimbabwe. We then trained community and family caregivers to use an app to communicate patient-reported outcomes to their palliative care providers each week on a data dashboard. App activity was monitored, and qualitative in-depth interviews explored experience with the app and its mechanisms and impact. RESULTS: N = 149 caregivers participated and uploaded n = 837 assessments of patient-reported outcomes. These data were displayed to the palliative care team on an outcomes dashboard on n = 355 occasions. Qualitative data identified: 1) high acceptability and data usage; 2) improved understanding by team members of patient symptoms and concerns; 3) a need for better feedback to caregivers, for better prioritisation of patients according to need, for enhanced training and support to use the app, and for user-led recommendations for ongoing improvement. CONCLUSION: An outcomes-focused app and data dashboard are acceptable to caregivers and health-care professionals. They are beneficial in identifying, monitoring, and communicating patient outcomes and in allocating staff resource to those most in need.
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Telefone Celular , Aplicativos Móveis , Humanos , Índia , Cuidados Paliativos , Uganda , ZimbábueRESUMO
BACKGROUND: Urogenital schistosomiasis and HIV/AIDS infections are widespread in sub-Saharan Africa (SSA) leading to substantial morbidity and mortality. The co-occurrence of both diseases has led to the possible hypothesis that urogenital schistosomiasis leads to increased risk of acquiring HIV infection. However, the available evidence concerning this association is inconsistent. The aim of this study was to systematically review and quantitatively synthesize studies that investigated the association between urogenital schistosomiasis and HIV/AIDS infection. METHODS: A systematic review basing on PRISMA guidelines was conducted. It is registered with PROSPERO, number CRD42018116648. We searched four databases, MEDLINE, EMBASE, Global Health and Global Index Medicus for studies investigating the association between urogenital schistosomiasis and HIV infection. Only studies published in English were considered. Results of the association were summarised by gender. A meta-analysis was performed for studies on females using random-effects model and a pooled OR with 95% confidence interval was reported. RESULTS: Of the 993 studies screened, only eight observational studies met the inclusion criteria. Across all studies, the reported unadjusted OR ranged from 0.78 to 3.76. The pooled estimate of unadjusted OR among females was 1.31 (95% CI: 0.87-1.99). Only four of the eight studies reported an adjusted OR. A separate meta-analysis done in the three studies among females that reported an adjusted OR showed that the pooled estimate was 1.85 (95% CI: 1.17-2.92). There were insufficient data to pool results for association between urogenital schistosomiasis and HIV infection in the males. CONCLUSION: Our investigation supports the hypothesis of an association between urogenital schistosomiasis with HIV/AIDS infection in females. Due to insufficient evidence, no conclusion could be drawn in males with urogenital schistosomiasis. Large-scale prospective studies are needed in future.