Evaluation of cost-effective strategies for rabies post-exposure vaccination in low-income countries

<b>Background:</b> Prompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized.<p></p> <b>Methodology/Principal Findings:</b> We analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than$60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs.<p></p> <b>Conclusions/Significance:</b> We conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers.<p></p&gt

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

<p><b>Background:</b> Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.</p> <p><b>Methodology/Principal Findings:</b> This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.</p> <p><b>Conclusions/Significance:</b> We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.</p&gt

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route: Results of a metaanalysis

The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986–2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India and Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) and human diploid cell vaccine (MIRV, France). The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route (p > 0.230 and p > 0.568)

Supercritical Carbon Dioxide Extract of Seabuckthorn Leaves Enhances Rabies Virus Neutralizing Antibody Titers and CTL Response in Swiss Albino Mice

Introduction: Rabies is a viral disease that causes nearly thousands of death globally per year. Vaccination against rabies generates virus neutralizing antibodies and is the most successful and cost effective method of preventing the disease. In the present study, we have evaluated the adjuvant property of supercritical carbon dioxide extract (SCE) 300ET of Seabuckthorn (SBT) leaves against inactivated rabies virus antigen in Swiss albino mice. Methods: Mice were grouped as PBS control; inactivated rabies antigen (Rb) control; 300ET+Rb and Algel+Rb. All the mice were primed on day 1 followed by single booster at day 14. Sera were collected at different time points for RVNA analysis. Additionally, the effect of SCE on CD8+Granzyme B+ Cytotoxic T Lymphocyte (CTL) response, surface markers and cytokine levels were measured. Result: The results showed enhanced rabies virus neutralizing antibody (RVNA) titres using 300ET as compared to control and Algel groups as measured by Rapid Fluorescent Focus Inhibition Test (RFFIT). Moreover, the extract 300ET and Algel showed increased CD138+ (plasma cells) and CD11c+ (dendritic cells) cell population as compared to the inactivated rabies antigen immunized mice. The extract 300ET also stimulated cellular immunity by showing heightened CTL response and proinflammatory cytokines level such as TNF-α and IL-1β. Conclusion: Hence, our results suggested that SCE 300ET exhibits adjuvant activity by effectively enhancing antibody as well as cell mediated immunity in response to rabies antigen. Thus,SCE could be considered as a potential adjuvant candidate for rabies vaccines.</p