Child malaria vaccine uptake in Ghana: Factors influencing parents' willingness to allow vaccination of their children under five (5) years.

BACKGROUND: Malaria is a substantial health burden in Ghana, particularly among children. Despite the availability of malaria vaccines, uptake remains low. Notwithstanding, there is a paucity of nationally representative studies on the factors driving hesitance towards the new malaria vaccine. In response, this study, guided by the Theory of Planned Behaviors (TPB), seeks to understand the determinants of child malaria vaccine uptake in Ghana to inform strategies for improving coverage. MATERIALS AND METHODS: We employed multiple regression model to examine the association between maternal awareness, socioeconomic status, ethnicity, geographical location, and vaccine uptake using data from the 2019 Ghana Malaria Indicator Survey (MIS). RESULTS: Maternal awareness of vaccine (OR = 2.200; P<0.01) significantly predicted higher likelihood of vaccine uptake. Household wealth was associated with child vaccination as parents in middle-income households (OR = 9.342; P<0.01), and those in poorest households (OR = 9.409; P<0.05) recorded higher likelihood of allowing their children to be vaccinated. With regards to ethnicity, parents from the Mande ethnic group (OR = 0.106; P<0.05) were less likely to allow their children to be vaccinated when compared to parents from the Akan ethnic group. Knowing that malaria is covered by National Health Insurance (OR = 2.407; P<0.05) was associated with higher likelihood of allowing child vaccination compared to not knowing. More so, geographical variations were observed as parents who lived in rural areas (OR = 0.254; P<0.05) were significantly less likely to allow vaccination of their children compared to those in urban areas. CONCLUSIONS: Enhancing awareness through education campaigns can improve child malaria vaccine coverage. Observing socioeconomic disparities in uptake and ensuring equitable access to vaccines are vital. Tailored strategies considering ethnic background and geographical location, can as well enhance acceptance of the vaccine. This study provides valuable insights for developing effective strategies to reduce the burden of malaria in children and improve coverage of uptake. This study underscores the need to improve parental awareness and the relevance of the vaccine in preventing child mortality.

A perspective on Oxford's R21/Matrix-M™ malaria vaccine and the future of global eradication efforts.

Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections and over 600,000 deaths across 85 countries. In the ongoing battle against malaria, a promising development has emerged with the endorsement by the World Health Organization (WHO) of the R21/Matrix-M™ Malaria Vaccine. Developed through a collaboration between the University of Oxford and Novavax, this vaccine has demonstrated remarkable efficacy, reaching 77% effectiveness in Phase 2 clinical trials. It is designed to be low-dose, cost-effective, and accessible, with approval for use in children under three years old. This perspective paper critically examines the R21/Matrix-M malaria vaccine, its development, potential impact on global malaria eradication efforts, and the challenges and opportunities it presents.

Commodifying Vaccines to Curtail Antibiotic Resistance Impact in Malaria Endemic Countries.

Rampant and prevalent deployment of an efficient malaria vaccine in Pakistan, together with basic control and preventive measures, could significantly decrease the economic and healthcare burden caused by drug-resistant malaria. Moreover, RTS, S/AS01 vaccine has attained a much-needed breakthrough after decades of growth, as an innovative vaccine for malaria in Phase III clinical trials, and presently undergoing implementation studies. So far Gavi, WHO, and other stakeholders are contemplating on the practical issues, risk-benefit, and cost-effectiveness in resource-limited settings of vaccine implementation capacity. Imminent advances, like using a delayed as well as enhanced protection, divided schedule for dosing, and alternate adjuvants are likely to attain the vital goal of eradication of malaria. Vaccination is a potentially critical component of efforts to arrest the development and dissemination of antimicrobial resistance; though little is known about the impact vaccination may have within low-and-middle-income countries. Key Words: Antimicrobial resistance, Malaria, Vaccine.

Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials?

BACKGROUND: Early phase malaria vaccine field trials typically measure malaria infection by PCR or thick blood smear microscopy performed on serially sampled blood. Vaccine efficacy (VE) is the proportion reduction in an endpoint due to vaccination and is often calculated as VEHR = 1-hazard ratio or VERR = 1-risk ratio. Genotyping information can distinguish different clones and distinguish multiple infections over time, potentially increasing statistical power. This paper investigates two alternative VE endpoints incorporating genotyping information: VEmolFOI, the vaccine-induced proportion reduction in incidence of new clones acquired over time, and VEC, the vaccine-induced proportion reduction in mean number of infecting clones per exposure. METHODS: Power of VEmolFOI and VEC was compared to that of VEHR and VERR by simulations and analytic derivations, and the four VE methods were applied to three data sets: a Phase 3 trial of RTS,S malaria vaccine in 6912 African infants, a Phase 2 trial of PfSPZ Vaccine in 80 Burkina Faso adults, and a trial comparing Plasmodium vivax incidence in 466 Papua New Guinean children after receiving chloroquine + artemether lumefantrine with or without primaquine (as these VE methods can also quantify effects of other prevention measures). By destroying hibernating liver-stage P. vivax, primaquine reduces subsequent reactivations after treatment completion. RESULTS: In the trial of RTS,S vaccine, a significantly reduced number of clones at first infection was observed, but this was not the case in trials of PfSPZ Vaccine or primaquine, although the PfSPZ trial lacked power to show a reduction. Resampling smaller data sets from the large RTS,S trial to simulate phase 2 trials showed modest power gains from VEC compared to VEHR for data like those from RTS,S, but VEC is less powerful than VEHR for trials in which the number of clones at first infection is not reduced. VEmolFOI was most powerful in model-based simulations, but only the primaquine trial collected enough serial samples to precisely estimate VEmolFOI. The primaquine VEmolFOI estimate decreased after most control arm liver-stage infections reactivated (which mathematically resembles a waning vaccine), preventing VEmolFOI from improving power. CONCLUSIONS: The power gain from the genotyping methods depends on the context. Because input parameters for early phase power calculations are often uncertain, these estimators are not recommended as primary endpoints for small trials unless supported by targeted data analysis. TRIAL REGISTRATIONS: NCT00866619, NCT02663700, NCT02143934.

Malaria & mRNA Vaccines: A Possible Salvation from One of the Most Relevant Infectious Diseases of the Global South.

Malaria is one of the most dangerous infectious diseases in the world. It occurs in tropical and subtropical regions and affects about 40% of the world´s population. In endemic regions, an estimated 200 million people contract malaria each year. Three-quarters of all global deaths (about 600 per year) are children under 5 years of age. Thus, malaria is one of the most relevant tropical and also childhood diseases in the world. Thanks to various public health measures such as vector control through mosquito nets or the targeted use of insecticides as well as the use of antimalarial prophylaxis drugs, the incidence has already been successfully reduced in recent years. However, to reduce the risk of malaria and to protect children effectively, further measures are necessary. An important part of these measures is an effective vaccination against malaria. However, the history of research shows that the development of an effective malaria vaccine is not an easy undertaking and is associated with some complications. Research into possible vaccines began as early as the 1960s. However, the results achieved were rather sobering and the various vaccines fell short of their expectations. It was not until 2015 that the vaccine RTS,S/AS01 received a positive evaluation from the European Medicines Agency. Since then, the vaccine has been tested in Africa. However, with the COVID-19 pandemic, there are new developments in vaccine research that could also benefit malaria research. These include, among others, the so-called mRNA vaccines. Already in the early 1990s, an immune response triggered by an mRNA vaccine was described for the first time. Since then, mRNA vaccines have been researched and discussed for possible prophylaxis. However, it was not until the COVID-19 pandemic that these vaccines experienced a veritable progress. mRNA vaccines against SARS-CoV-2 were rapidly developed and achieved high efficacy in studies. Based on this success, it is not surprising that companies are also focusing on other diseases and pathogens. Besides viral diseases, such as influenza or AIDS, malaria is high on this list. Many pharmaceutical companies (including the German companies BioNTech and CureVac) have already confirmed that they are researching mRNA vaccines against malaria. However, this is not an easy task. The aim of this article is to describe and discuss possible antigens that could be considered for mRNA vaccination. However, this topic is currently still very speculative.

First malaria vaccine slashes childhood deaths.

Final evaluation brings good news from RTS,S rollout.

Second malaria vaccine gets WHO green light.

New shots could make malaria protection more plentiful, saving tens of thousands of lives.

Pre-vaccination monocyte-to-lymphocyte ratio as a biomarker for the efficacy of malaria candidate vaccines: A subgroup analysis of pooled clinical trial data.

BACKGROUND: Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI). METHODS: We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted. RESULTS: The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45-1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51-2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80). CONCLUSION: Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination.

Malaria Vaccines: Progress to Date.

Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality over the last two decades, it remains a major public health burden in many countries. This underscores the critical need for improved strategies to prevent, treat and control malaria if we are to ultimately progress towards the eradication of this disease. Ideally, this will include the development and deployment of a highly effective malaria vaccine that is able to induce long-lasting protective immunity. There are many malaria vaccine candidates in development, with more than a dozen of these in clinical development. RTS,S/AS01 (also known as Mosquirix) is the most advanced malaria vaccine and was shown to have modest efficacy against clinical malaria in phase III trials in 5- to 17-month-old infants. Following pilot implementation trials, the World Health Organisation has recommended it for use in Africa in young children who are most at risk of infection with P. falciparum, the deadliest of the human malaria parasites. It is well recognised that more effective malaria vaccines are needed. In this review, we discuss malaria vaccine candidates that have progressed into clinical evaluation and highlight the most advanced candidates: Sanaria's irradiated sporozoite vaccine (PfSPZ Vaccine), the chemoattenuated sporozoite vaccine (PfSPZ-CVac), RTS,S/AS01 and the novel malaria vaccine candidate, R21, which displayed promising, high-level efficacy in a recent small phase IIb trial in Africa.

[Vaccination against malaria]. / Vaccination contre le paludisme.

Vaccination against malaria is an old dream that reemerged in 2015 with the European Medicines Agency's favourable opinion on a first antimalarial vaccine, RTS,S/ AS01. Six years later, the World Health Organization (WHO) is advising a wide deployment of this vaccine in sub-Saharan Africa and in regions with high and moderate transmission where Plasmodium falciparum circulates. This follows favourable results from the pilot programme in Ghana, Kenya and Malawi involving over 800,000 children since 2019. This article addresses the objectives and main vaccine candidates targeting the different stages of parasite development, highlighting the progress and limitations of these different approaches. The RTS,S saga has been a milestone in vaccine development, with a first-generation vaccine recommended by the WHO for use in children over 5 months of age in sub-Saharan Africa and other areas of moderate to high transmission of P. falciparum malaria, in combination with other prevention measures. Research efforts continue to better understand the correlates of protection. With advances in vaccine platforms, new multi-antigen, multi-stage, and even multi-species approaches might emerge and brighten the horizon for malaria control.

Malaria vaccines to moderate the impact of antibiotic resistance in endemic countries.

Swift and widespread deployment of an efficient malaria vaccine in Pakistan, together with basic control and preventive measures, could significantly decrease the economic and healthcare burden caused by drug-resistant malaria. Moreover, the RTS,S/AS01 vaccine has provided a much needed breakthrough after decades of growth, as an innovative vaccine for malaria in phase 3 clinical trials and currently undergoing implementation studies. Vaccination is a potentially critical component of efforts to arrest the development and dissemination of antimicrobial resistance, although little is known about the impact vaccination may have within low- and-middle-income countries.

Acceptance, availability, and feasibility of RTS, S/AS01 malaria vaccine: A review.

INTRODUCTION: In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically decreased because of artemisinin-based pharmacological regimens. METHODS: Two independent researchers did a comprehensive literature search using PubMed/MEDLINE and Google Scholar from its inception to September 2022. RESULTS: After evaluating RTS, S/AS01 for its safety, effectiveness, and feasibility, the European Medicines Agency (EMA) issued a favorable conclusion. It was suggested that the RTS, S malaria vaccine be used extensively by the World Health Organization on October 6, 2021. The successful pilot program testing the malaria vaccine in Ghana, Kenya, and Malawi served as the basis for this proposal. CONCLUSION: Several challenges need to be addressed to ensure the success of vaccination programs. From the acceptability perspective, issues such as inadequate community engagement, concerns about side effects, and issues with the delivery and quality of healthcare services can affect the acceptance of the vaccine. From the feasibility standpoint, factors such as lack of transportation or long distances to healthcare facilities and the perception of completion of the vaccination calendar can affect the feasibility of the vaccine. Lastly, the availability of the vaccine is also a major concern as it may not be readily available to meet the demands.

Delivery strategies for malaria vaccination in areas with seasonal malaria transmission.

BACKGROUND: Seasonal vaccination with the RTS,S/AS01E malaria vaccine given alongside seasonal malaria chemoprevention (SMC) substantially reduces malaria in young children. The WHO has recommended the use of RTS,S/AS01E, including seasonal vaccination, in areas with seasonal malaria transmission. This study aimed to identify potential strategies to deliver RTS,S/AS01E, and assess the considerations and recommendations for delivery of seasonal malaria vaccination in Mali, a country with highly seasonal malaria. METHODS: Potential delivery strategies for RTS,S/AS01E in areas with seasonal malaria were identified through a series of high level discussions with the RTS,S/AS01E plus SMC trial investigators, international and national immunisation and malaria experts, and through the development of a theory of change. These were explored through qualitative in-depth interviews with 108 participants, including national-level, regional-level and district-level malaria and immunisation programme managers, health workers, caregivers of children under 5 years of age, and community stakeholders. A national-level workshop was held to confirm the qualitative findings and work towards consensus on an appropriate strategy. RESULTS: Four delivery strategies were identified: age-based vaccination delivered via the Essential Programme on Immunisation (EPI); seasonal vaccination via EPI mass vaccination campaigns (MVCs); a combination of age-based priming vaccination doses delivered via the EPI clinics and seasonal booster doses delivered via MVCs; and a combination of age-based priming vaccination doses and seasonal booster doses, all delivered via the EPI clinics, which was the preferred strategy for delivery of RTS,S/AS01E in Mali identified during the national workshop. Participants recommended that supportive interventions, including communications and mobilisation, would be needed for this strategy to achieve required coverage. CONCLUSIONS: Four delivery strategies were identified for administration of RTS,S/AS01E alongside SMC in countries with seasonal malaria transmission. Components of these delivery strategies were defined as the vaccination schedule, and the delivery system(s) plus the supportive interventions needed for the strategies to be effective. Further implementation research and evaluation is needed to explore how, where, when and what effective coverage is achievable via these new strategies and their supportive interventions.