Amendment to anti rabies post exposure therapy (PET) protocol

Dr. Kanthi Nanayakkara
Head / department of Rabies and Vaccine Q C,
Medical Research Institute, Colombo 8.

Rabies is a viral infection caused by a lyssa virus. It is a zoonotic disease which is prevalent among mammals. Rabies is endemic in Sri Lanka and the main carrier identified in transmitting the disease to humans is the dog followed by cats and other wild animals.
Transmission is usually through infected saliva via a bite of an infected animal, saliva contaminated scratches or a lick on broken skin or mucous membranes. The virus targets nervous tissue and will enter the peripheral nerves and travels up along the spinal cord to the brain stem and the brain, causing an invariably fatal encephalo-myelitis.

The incubation period of rabies depends on the size of the inoculum as well as the distance from the viral entry to the central nervous system. It may be as short as few days or as long as few years, but is usually around 1 – 3 months.

Rabies is 100% fatal without anti rabies prophylaxis (pre exposure or post exposure). The comparatively long incubation period provides an opportunity for highly effective PET.

PET consists of: (i) thorough washing and flushing of the wound; (ii) a series of rabies vaccine administrations started immediately after an exposure, and if indicated (iii) Rabies Immunoglobulin (RIG) infiltration into and around the wound, promptly after exposure.
In Sri Lanka anti rabies pre and post exposure prophylaxis is offered free of charge to people who are at risk of rabies, from most government hospitals throughout the country except few very small hospitals. Rabies PET is done according to a DGHS circular which has been based on available WHO recommendations and country experiences, to make the treatment uniform in all hospitals in the country. By adhering to this protocol patients following animal exposures will receive correct and the recommended treatment. In addition, by avoiding unnecessary vaccinations, wastage of expensive biologicals with limited availability can be prevented. Periodic revisions to this circular has been carried out, with the introduction of tissue culture vaccines in the entire country, implementation of intra dermal (ID) ARV schedules and changes in the ID protocols, all of which has been done according to WHO guidelines. The present PET protocol was issued in March 2016 - DGHS/Circular2016-127(MRI-ARPET). According to this protocol, it was recommended to do a sensitivity test (ST) prior to administering equine rabies immunoglobulin (ERIG) for major exposures and the volume was calculated according to the patient’s body weight (20IU/Kg). After infiltrating all the wounds adequately, any remaining ERIG was injected IM on the thighs.

On 20th of April 2018, the WHO released its latest position paper on rabies (Weekly Epidemiological Record - WHO, 20 April 2018, No16,2018,93,201-220). This position paper replaces the 2010 WHO position on rabies vaccines. It presents new evidence in the field of rabies and the use of rabies vaccines, focusing on programmatic feasibility, simplification of vaccination schedules and improved cost-effectiveness. Among other recommendations regarding rabies PET, there were two major changes on the administration of ERIG in this new position paper.

For optimal effectiveness, the maximum dose calculation for RIG is 40 IU/kg body weight for equine derived RIG (ERIG), and 20 IU/kg body weight for human derived RIG (HRIG).
Administration of rabies immunoglobulin (RIG)

• The present WHO guideline does not recommend skin testing (ST) before administration of Equine Rabies Immunoglobulin (ERIG), as such tests poorly predict severe adverse events and their results should not be the basis for non-administration of ERIG when indicated

• However the treating medical officers should be prepared to manage anaphylaxis, which although rare, could occur during the administration of ERIG

• Maximum dose of ERIG is 40IU/kg of body weight. There is no minimum dose

• The entire immunoglobulin dose or as much as anatomically feasible should be infiltrated carefully into or as close as possible to all wounds

• WHO no longer recommends injecting the remainder of the calculated RIG dose IM at a distance from the wound as evidence suggest that there is no or little additional protection against rabies as compared with infiltration of the wound/s alone

An amendment to the existing ARV PET protocol was issued including these recommendations under the Director General of Health Services on the 10th of July 2018 with the following recommendations.

Considering the WHO guidelines on Rabies PET (2018),
 ST should no longer be performed before administering ERIG
 RIG should be infiltrated as much as possible to the site of the wound/s only
A course of ARV should always follow the infiltration of RIG

1. Vaccines and rabies immunoglobulins for humans, WHO Expert Consultation on Rabies, WHO Technical Report Series:2018:1012 (3)
2. Rabies vaccines: WHO position paper, Weekly epidemiological record, WHO, 20 April 2018,No 16,2018,93, 201-220

CME February – Application of MALDI-TOF MS in Clinical Microbiology

Dr. Subodha Wickramasinghe (MD), Lecturer, Department of Microbiology, Faculty of Medicine, University of Ruhuna Delivered a lecture on “Application of MALDI-TOF MS (Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry) in Clinical Microbiology ” . 01st of February 2019 .

A rapid and accurate microbiological diagnosis is associated with decreased mortality and reduced length of hospitalization, especially for severe, life threatening infections. This also allows for early streamlining of empirical antimicrobial therapies, contributing to limit the emergence and spread of antimicrobial resistance.
The introduction of matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) for routine identification of microbial pathogens has profoundly influenced microbiological diagnostics, and is progressively replacing biochemical identification methods.

Compared to currently used identification methods, MALDI-TOF MS has the advantage of identifying bacteria and yeasts directly from colonies grown on culture plates for primary isolation in a few minutes and with considerable material and labor savings. The reliability and accuracy of MALDI-TOF MS in identification of clinically relevant bacteria and yeasts have been demonstrated by several studies showing that the performance of MALDI-TOF MS is comparable or superior to phenotypic methods currently in use in clinical microbiology laboratories, and can be further improved by regular database updates and analysis software upgrades.

Even though the DNA sequencing can identify fastidious and uncultivable microorganisms, the requirement of trained laboratory personnel, powerful interpretation soft wares, expensive materials, makes it less suitable for routine clinical use.
In comparison, MALDI TOF MS requires high initial cost for the MALDI-TOF equipment. But the ability to obtain an accurate microbiological diagnosis within a few minutes without trained laboratory personnel and reduced cost per test and reduced hands-on-time allows MALDI-TOF MS system more superior than other detection methods in a clinical microbiology laboratory.

Other limitations of MALDI TOF MS are the limit of resolution among closely related organisms like Shigella and E.coli, similarities of spectra present in the database as for viridans streptococci and pneumococci and for yeasts requiring a protein extraction procedure for correct identification as insufficient protein signal by direct colonies.
At present many laboratories rely on MALDI-TOF MS for routine identification of microbial pathogens, and use other identification systems like genome sequencing to confirm uncertain (low-score value by MALDI-TOF MS) identifications to achieve correct identification rates.
Besides microbial identification from isolated colonies, new perspectives are being explored for MALDI-TOF MS, such as identification of pathogens directly from positive blood cultures, sub-species identification and strain typing, assessment of drug susceptibility and detection of drug resistance determinants.

In conclusion, MALDI-TOF MS is a tool for rapid, accurate, and cost-effective identification of microorganisms and applicable to a broad range of common as well as esoteric bacteria including mycobacterial spp. and fungi and has become an incontrovertibly beneficial technology in a clinical microbiology laboratory.

Florio W, Tavanti A, Barnini S, Ghelardi E and Lupetti A (2018)Recent Advances and Ongoing Challenges in the Diagnosis of Microbial Infections by MALDI-TOF Mass Spectrometry. Front. Microbiol. 9:1097.
doi: 10.3389/fmicb.2018.01097
Robin Patel (2015). MALDI-TOF MS for the Diagnosis of Infectious Diseases, Clinical Chemistry 61:1 100–111

OGM January 2019

An Ordinary General Meeting of the Sri Lanka College of Microbiologists was held at the Aldo Castellani Auditorium of the Medical Research Institute on 4th of January 2019.

This was chaired by Prof. Ajith Nagahawatte, President of the SLCM 2018-2019.

Thirty-three members were present and 10 members were excused for the meeting.

President informed that the newly appointed company secretary has completed the process of registering of new board of Directors of the SLCM. He tabled the progress of the Revision of Hospital Infection Control Manual and the AMR project of the College. He also informed that there was a new Fleming Fund project being advertised but the SLCM would not be applying for it as the magnitude of the project was beyond the scope of the College.

He announced that the Annual Scientific Sessions 2019 will be held on 13th, 14th and 15th August 2019 at Hotel Ramada.

The membership agreed to have an annual one-day trip for the families as a new activity.

It was also decided to implement more activities such as an Antibiotic Awareness Walk and the use of social media and already developed education material to disseminate antimicrobial stewardship among health care workers and the general public.