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

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Effects of AGT and AGTR1 Genetic Polymorphisms and Changes in Blood Pressure Over a Five-Year Follow-Up

Siwaphorn Chaimati,1 Prapimporn Chattranukulchai Shantavasinkul,2 Piyamitr Sritara,2 Jintana Sirivarasai3 1Doctoral Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University, Bangkok, 10400, Thailand; 2Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 3Nutrition Division, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, ThailandCorrespondence: Jintana Sirivarasai, Nutrition Division, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +662-201-1483, Fax +662-201-2625, Email [email protected]: The renin–angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1) may increase susceptibility to elevated BP and hypertension. This study investigated the effects of AGT rs699 and AGTR1 rs5186 single nucleotide polymorphisms (SNPs) on BP at baseline and at a 5-year follow-up.Paticipants and Methods: The study population consisted of participants from the Electricity Generating Authority of Thailand cohort study (n=354); data were collected at baseline (2013) and 5 years later (2018). Genotyping of the two SNPs was performed using TaqMan® assay and statistical analyses were performed with SNPStats software.Results: The frequencies of the two SNPs were within the Hardy–Weinberg equilibrium (p=0.22 for AGT rs699 and p=0.06 for AGTR1 rs5186). For each SNP, mutant genotypes were significantly associated with increased systolic BP and/or diastolic BP in the codominant and recessive models. Risk alleles of AGT rs699 and AGTR1 rs5186 were associated with increased odds of hypertension and hypertension with metabolic syndrome at follow-up.Conclusion: Overall, our results suggest that polymorphisms of genes in the renin–angiotensin system increase susceptibility to the development and progression of hypertension and the development of the metabolic syndrome.Keywords: angiotensinogen, angiotensin II receptor type 1, polymorphisms, hypertension, metabolic syndrom

Reemergence of Rabies in Chhukha District, Bhutan, 2008

TOC summary: A major outbreak affected dogs, domestic livestock, and humans

Using serology to assist with complicated post-exposure prophylaxis for rabies and Australian bat lyssavirus

Background: Australia uses a protocol combining human rabies immunoglobulin (HRIG) and rabies vaccine for post-exposure prophylaxis (PEP) of rabies and Australian bat lyssavirus (ABLV), with the aim of achieving an antibody titre of >= 0.5 IU/ml, as per World Health Organization (WHO) guidelines, as soon as possible