Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies

Omesh Kumar Bharti Faculty Epidemiologist^a^*, Shampur Narayan Madhusudana Professor of Neurovirology, Head^b, Pyare Lal Gaunta Sr.Medical Superintendent^c & Ashwin Yajaman BelludiSenior Resident, Neurovirology^d

Presently the dose of rabies immunoglobulin (RIG) which is an integral part of rabies post exposure prophylaxis (PEP) is calculated based on body weight though the recommendation is to infiltrate the wound(s). This practice demands large quantities of RIG which may be un- affordable to many patients. In this background, we conducted this study to know if the quantity and cost of RIG can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular administration based on the available scientific evidence. Two hundred and sixty nine category III patients bitten by suspect or confirmed rabid dogs/ animals were infiltrated with equine rabies immunoglobulin (ERIGs) in and around the wound, the quantity of ERIG used was proportionate to the size and number of wounds irrespective of their body weight. They were followed with a regular course of rabies vaccination by intra-dermal route. As against 363 vials of RIGs required for all these cases as per current recommendation based on body weight, they required only 42 vials of 5ml RIG. Minimum dose of RIGs given was 0.25ml and maximum dose given was 8 ml. On an average 1.26 ml of RIGs was required per patient that costs Rs. 150 ($3). All the patients were followed for 9 months and they were healthy and normal at the end of observation period. With local infiltration, that required small quantities of RIG, the RIGs could be made available to all patients in times of short supply in the market. A total of 30 (11%) serum samples of patients were tested for rabies virus neutralizing antibodies by the rapid fluorescent focus inhibition test (RFFIT) and all showed antibody titers >0.5 IU/mL by day 14. In no case the dose was higher than that required based on body weight and no immunosuppression resulted. To conclude, this pilot study shows that local infiltration of RIG need to be considered in times of non availability in the market or un-affordability by poor patients. This preliminary study needs to be done on larger scale in other centers with long term follow up to substantiate the results of our study.
The link; http://www.tandfonline.com/doi/full/10.1080/21645515.2015.1085142#.VeRiU_mqqko

Also other low cost solutions are described in the link below, copy and paste in Google for details;

http://www.scirp.org/journal/PaperInformation.aspx?PaperID=58107

Background: Rabies is a dreaded disease and an estimated 55,000 people die of rabies every year. Himachal Pradesh is in the North bordering China and is predominantly rural and hilly. Villages are near forests, where wild reservoirs of rabies exist. Since health facilities are not accessible easily, we need to innovate on existing schedules of rabies vaccination keeping in view the compliance of the patients and affordability so as to give them the best possible option of treatment. In the year 2006 and 2007, we, at DDU Hospital Shimla, experienced a severe shortage of rabies vaccine and patients were running from pillar to post to fetch rabies vaccine. At the same time, we learnt that some of the patients died because either they were not able to purchase the vaccine, mostly because of its high cost, $35, or they ignored the animal bites and did not seek the treatment. Since last year, we have been experiencing non-availability of rabies immunoglobulins (RIGs) in the market and have to innovate new schedules and techniques to save lives of the patients. Methods: During shortage of rabies vaccine in 2008, we contemplated to start a low cost intra-dermal (ID) clinic so as to make rabies vaccine affordable as intramuscular (IM) vaccination cost five times more than ID vaccination. But, there were three main hurdles. One hurdle was the non-availability of rabies vaccine vials having written on them “For IM/ID use” and another hurdle was only fewer animal bite patients attending the DDU Hospital, sometimes only one or two per day, which was insufficient to open a vaccine vial and distribute among them. The third problem being faced was reluctance of the hospital doctors to prescribe ID vaccine as this was not the practice at higher teaching institutions, including medical colleges. We contacted a vaccine company and few vials labeled as “For IM/ID use” were sourced from Mumbai (1200 km away from here). We asked the Chief Medical Officer, Shimla district to write a letter to all health facilities around our Hospital to give first aid to animal bite patients and then refer them to DDU Hospital for vaccination. Now we were able to pool the patients and divide a single 1 ml vaccine vial among four patients. After continuous advocacy, our stress that WHO has given its approval for ID use of rabies vaccine and that subsequent approval has been granted by Government of India was enough for doctors to prescribe the vaccine as ID. Last Year, we got ethical approval to inject rabies Immunoglobulins (RIGs) only locally in and around the wound at times of scarcity of RIGs in the market. The subsequent follow up of patients proved life saving in crisis of shortage of RIGs. Due to shortage of RIGs we innovatively vaccinated people bitten by rabid dogs or people who had consumed rabid cow’s milk and followed them for outcome, apart from having Rabies Fluorescent Focus Inhibition Test (RFFIT) was done for few of the patiens for verification of protective titers. We innovated a technique of extraction of last drop of vaccine from the vial and also saved a drop of RIGs being used for test dose before giving RIGs to the patients. Results: The first low cost anti-rabies clinic was started on August 2, 2008 after long advocacy sessions with the authorities and the doctors. Since then, we have done many innovations based on local requirements and patients’ feedback and accessibility to treatment. We have given pre and post-exposure prophylaxis to more than 12,000 animal bite victims over more than five years period in this single clinic, saving lives as well as money without any failure even in difficult rabid animal bite cases. Our innovation helped us save the vaccine and immunoglobulins till the last drop. Conclusions: Innovative ways by health providers backed by extensive literature review and scientific evidence can help patients get low cost health deliverables that increase their compliance as medicines/vaccines become affordable to them. Third world countries need to innovate their own ways to solve their problems of scanty resources and find innovative solutions to conquer them, rather than looking elsewhere for solutions.

Innovations for poor

Saturday 14 November 2015

Soon a low cost solution to save animals bitten by rabid dogs in the offing soon

Monday 31 August 2015

Low cost solution to animal bite victims- life saving for the poor of Asia and Africa is here !

Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies

Thursday 9 July 2015

Friday 6 February 2015

my Research papers for benefit of humanity