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

Abstract

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 unaffordable 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 0.25 ml 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 unaffordability 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.

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“…Due to limited RIG availability, patients (N = 700, median age: 30 years, median weight: 53 kg, sex ratio: 63:37 male:female) were administered RIG under a dose-sparing approach of infiltration of the wound only. All survived on follow-up [8,9]. We used bootstrap sampling of these data, where patient weight was measured, to capture variability in RIG use under two scenarios: (1) infiltration at the wound (s) with the remainder administered intramuscularly distant from the wound; and (2) infiltration of the wound(s) only.…”

“…The previous WHO recommendation calculates dosage according to patient body weight, with as much RIG as is anatomically possible being administered into and around the wound(s) and the remaining product being injected intramuscularly distant from the wound [4]. New evidence led to revised protocols for administering RIG at the wound only [8,9]. RIG vials can be shared between patients using single-use injection devices, but opened vials should also be discarded at the end of each day.…”

Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG

“…1 One major barrier to Post Exposure Prophylaxis (PEP) continues to be the high cost of rabies immunoglobulins (RIG) which can be bridged by injecting RIG into the wounds only, and omitting intramuscular administration of the remaining part that was not used for wound injection. 2 An increasing number of dog bite victims were being presented to public hospitals in Himachal Pradesh, India in 2014 amidst virtual non availability of RIG. 2 Only a small quantity of eRIG was available from the government owned Central Research Institute (CRI) Kasauli.…”

“…2 An increasing number of dog bite victims were being presented to public hospitals in Himachal Pradesh, India in 2014 amidst virtual non availability of RIG. 2 Only a small quantity of eRIG was available from the government owned Central Research Institute (CRI) Kasauli. We were 'forced' to do this study given limited availability of eRIG.…”

Exploring the Feasibility of a New Low Cost Intra-Dermal Pre & Post Exposure Rabies Prophylaxis Protocol in Domestic Bovine in Jawali Veterinary Hospital, District Kangra, Himachal Pradesh, India

“…A recent study by Bharti and Madhusudana et al has shown that local infiltration of rabies immunoglobulins (RIGs) in and around wounds [8] is effective in preventing rabies even in lab confirmed rabid dog bite human patients and prompted us to do this study in animals to save their lives.…”