Community perceptions of malaria and vaccines in the South Coast and Busia regions of Kenya

<p>Abstract</p> <p>Background</p> <p>Malaria is a leading cause of morbidity and mortality in children younger than 5 years in Kenya. Within the context of planning for a vaccine to be used alongside existing malaria control methods, this study explores sociocultural and health communications issues among individuals who are responsible for or influence decisions on childhood vaccination at the community level.</p> <p>Methods</p> <p>This qualitative study was conducted in two malaria-endemic regions of Kenya--South Coast and Busia. Participant selection was purposive and criterion based. A total of 20 focus group discussions, 22 in-depth interviews, and 18 exit interviews were conducted.</p> <p>Results</p> <p>Participants understand that malaria is a serious problem that no single tool can defeat. Communities would welcome a malaria vaccine, although they would have questions and concerns about the intervention. While support for local child immunization programs exists, limited understanding about vaccines and what they do is evident among younger and older people, particularly men. Even as health care providers are frustrated when parents do not have their children vaccinated, some parents have concerns about access to and the quality of vaccination services. Some women, including older mothers and those less economically privileged, see themselves as the focus of health workers' negative comments associated with either their parenting choices or their children's appearance. In general, parents and caregivers weigh several factors--such as personal opportunity costs, resource constraints, and perceived benefits--when deciding whether or not to have their children vaccinated, and the decision often is influenced by a network of people, including community leaders and health workers.</p> <p>Conclusions</p> <p>The study raises issues that should inform a communications strategy and guide policy decisions within Kenya on eventual malaria vaccine introduction. Unlike the current practice, where health education on child welfare and immunization focuses on women, the communications strategy should equally target men and women in ways that are appropriate for each gender. It should involve influential community members and provide needed information and reassurances about immunization. Efforts also should be made to address concerns about the quality of immunization services--including health workers' interpersonal communication skills.</p

MALVAC 2008: Measures of efficacy of malaria vaccines in phase 2b and phase 3 trials--scientific, regulatory and public health perspectives.

The WHO Initiative for Vaccine Research and Global Malaria Programme convened a joint scientific forum in June 2008 to discuss scientific, regulatory and public health perspectives on the measurement of efficacy in malaria vaccine field efficacy trials. Participants included clinical trialists, statisticians and epidemiologists from both developed and developing countries, vaccine researchers and developers from academia and industry, and representatives of regulatory agencies. The efficacy of a vaccine against a disease is a summary indication of the extent to which those vaccinated are protected. However, there are several ways of measuring this and for high incidence diseases, such as malaria, in which there is variation in exposure and susceptibility from person to person, the choice of the appropriate measure of efficacy is more complex than is the case for low incidence diseases. There was agreement amongst statisticians at the meeting that basing analyses on "time to event" is the most appropriate method to analyse both incident infection and clinical malaria data from trials. However, policymakers would need to understand that this measure is different from that based on the proportion event-free up to a defined time, which has been used in reporting clinical challenge trials of malaria vaccines. For the assessment of public health impact, data should be reported on all episodes of malaria that a trial subject experiences, not only first episodes, and on duration of efficacy. Further research is required on the analysis of such multiple episode data. It will also be important to examine end-points such as severe malaria and death, though it may be difficult for the latter to be a primary end-point in trials. In order to compare findings in trials, it was suggested that efficacy estimates are reported at different time intervals after vaccination and that data sharing should be enhanced for all malaria vaccine clinical trials. It was appreciated that the epidemiology of malaria is changing in many settings and this may affect the public health benefit of a newly available malaria vaccine, whose likely impact would have to be assessed in the context of multiple other potential control measures. Research into possible interactions between malaria control measures was highlighted as a priority

Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation.

In October 2006, the World Health Organisation (WHO) convened a meeting of experts to discuss appropriate methods for evaluating the efficacy of malaria vaccines in pivotal phase III trials. The participants included regulatory, industry and donor representatives and clinical trialists, epidemiologists and statisticians from both developed and developing countries. The consultation also considered the regulatory requirements for registration of a malaria vaccine and public health issues that clinical development plans need to address before deployment of a malaria vaccine in developing countries. This report summarizes the discussions and conclusions reached during the course of the meeting. While the global public health burden of malaria is unquestionable there has been considerable variation in the ways in which a case of clinical disease due to malaria has been defined. In designing trials of malaria vaccines it is important that, to the extent possible, definitions of both clinical malaria and severe malaria are agreed that have high specificity and good sensitivity. There was general agreement on how these definitions should be determined, which should facilitate the clinical evaluation of vaccine candidates in paediatric populations in malaria endemic countries. There was agreement that trials of products that might be expected to have lower efficacy than most other vaccines in routine use for other diseases was justified as even partially effective malaria vaccines may be an important tool for reducing the large burden of disease due to malaria globally. Such products would be most easily deployed if they were designed to be administered with other EPI vaccines, which would be appropriate as the greatest burden of malaria is in infancy and early childhood. The conduct of pivotal trials poses special challenges both because the expected efficacy of immediately foreseeable vaccines is likely to be less than 50% and while malaria is a very common disease, distinguishing it from other conditions is far from straightforward. Therefore, in order to facilitate the interpretation of the results from trials, in particular for regulatory decision-making, it is essential that, insofar as is possible, methods that are used to define the clinical endpoints in such trials are standardised and validated. Cogent cases can be made for using either uncomplicated malaria disease or severe disease as the primary endpoint in pivotal trials, as both impose an enormous public health burden. The decision on which of these is most appropriate will be influenced by both scientific and non-scientific factors. Public health authorities might be more likely to accelerate introduction of a vaccine if an effect on severe disease had been demonstrated in a pivotal trial. Such decisions would also be influenced by knowledge of the efficacy of the vaccine in different malaria endemic settings and by knowledge of the duration of protection conferred post-vaccination. While phase IV studies may be necessary to generate some of this information, it is important to design pivotal trials to provide this information to the extent possible

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist

Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.

BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection