CHALLENGES IN RABIES DIAGNOSIS : THE SARAWAK EXPERIENCE

THE BEGINNING OF SARAWAK RABIES CHAPTER EPIDEMIC IN 2017

Rabies Outbreak was declared on 1st

July 2017 by DG of Health Malaysia

SPS CPD SEMINAR 2019

IT IS EASY TO DECLARE AN OUTBREAK BUT TO ESTABLISH THE DIAGNOSIS IS NOT EASY

In Northern State of Peninsular

Malaysia –Perlis, Kedah &

Penang reported canine rabies

outbreak on 27th July, 2015. It

resolved on 3rd Nov,2015.Bamaiyi P.H J. Vet. Adv., 2015, 5(12): 1181-

1190

CHILDREN FROM SERIAN

Admitted to Paediatric ICU ( PICU ) with neurological manifestations with an unknown diagnosis / aetiology

Viral / Autoimmune meningo-encephalitis

Poisoning

FINALLY....

One of the victim family gave history of “Dog Bite”and gave “Description of the dog behaviour that had bitten the victim and eventually died”, that triggered the possibility of Rabies.

THE MISSED DIAGNOSIS 38 year old lady, Bidayuh

Presented to Hospital Serian on 16th May 2017Bilateral lower limb weakness which was worsening x 3 days Fever x 2 daysNo bowel opening and passing flatus x 4 days

History of dog bite ( stray ) on 29th March 2017 at Kampung Remun.

Diagnosis on referral : GBS Acute Flaccid Paralysis 2o Rabies Intestinal Obstruction

PHYSICAL EXAMINATION

Upper Limb – Power 5/5, Reflexes – all present, Sensory – intact

Lower Limb - Reflexes – all absent, Babinski – Equivocal , Sensory – intact

Right Left

Hip Flexion 1/5 3/5

Extension 2/5 3/5

Knee Flexion 1/5 3/5

Extension 1/5 4/5

Ankle Dorsi Flexion 2/5 5/5

Plantar Flexion 5/5 5/5

OTHER MANAGEMENT

Referred to surgical for intestinal obstruction

Abdomen – soft, non tender, mildly distended, bowel sound –sluggish

Anal tone –lax

Impression : Ileus

( Na – 132, K – 3.3 , Urea- 3.6 )

Referred to orthopaedic for right lower limb pain

Impression : Unlikely spinal lesions.

PROGRESS

LP was performed ( 15/5/2017 )

Opening pressure – 18cmH20

CSF- blood stained, DS – No organism seen, Cells- All LØ, RBC- 3+

CSF – Protein 1.619, Pandy +ve, Chloride – 119, Glucose -4.2 ( HPC -7.1 )

CSF culture – No growth.

MRI Spine with contrast ( 19/5/2017 )

Mild enhancement of conus medullaris and cauda equine. No sign of spinal cord compression or transverse myelitis.

PROGRESS

Patient became confused, developed drop in GCS

She was ventilated and given 5 days course of IVIG

Despite that, condition deteriorated and died on 24th May 2017.

WHAT ARE THE LESSONS LEARNT ?

1. We should keep an open mind and get a good clinical history.

2. We should have a clinical diagnosis up in our mind which need to be tied up with laboratory diagnosis rather than the other way round.

3. There are likely more cases of missed diagnosis as clinicians are unfamiliar with the clinical presentation of the patient and don't get good clinical history.

SPS CPD SEMINAR 2018

28 SEPT 2018

WHAT CAN WE LEARNT FROM THE SARAWAKOUTBREAK FROM 2017 TILL NOW ?

Malaysia, including Sarawak is always at risk for cannine rabies outbreak resulting in human cases and death.

We must learnt from our past mistakes :

Poor animal surveillance

Inability to connect the dots ( putting bit and pieces of information together and make a diagnosis ) - No human animal ( dogs/ cats / monkeys ) bite surveillance data.

THE DIFFERENCE

In Sarawak state:

1. We diagnosed rabies through human cases.

2. Cats were also detected positive for rabies.

END HOST

EFFECTIVE

TRANSMITTOR

Dogs: 3-8 weeks Human: 4-12 weeks

RABIES VIRUS ( RV )

RV is a single-stranded, negative-sense neurotropic RNA virus that belongs to the Rhabdoviridae family, genus Lyssavirus.

RV can infect almost all mammals, including humans.

Dogs, wild carnivores and bats are the natural reservoirs of RV.

It causes acute encephalomyelitis.

The major defining characteristics of RV are its neuro-invasiveness, neurotropism and neurovirulence.

RABIES INFECTION

95% of human rabies was infected from exposure to dog bites (developing countries).

The mortality rate is 99.9% in the absence of timely

administration of PEP.

Important to know that after animal bite, there is no blood test to know if you are infected with rabies.

HOW IS RABIES TRANSMITTED?

Saliva containing rabies virus introduced into a bite wound.

Saliva or brain tissue from a rabid animal contacts a fresh wound or mucous membrane (i.e., lining of the eyes, nose, mouth, genitalia).

Corneal and organ transplants.

No transmission of rabies have been documented from infected patients to health care personnel or household contacts or by fomites or environmental surfaces

SGH SARAWAK 2017

3mm/hr

8-20mm/day

Pathogenesis

CLINICAL MANIFESTATIONS

SGH SARAWAK 2017

Generally : 3-8 weeks

1-3% : > 6 months

Fulminant : 5-6 days

• Viral load

innoculated

• Innoculation site

• Density of

innervations

5 days to 2 weeks

INFECTIVITY PERIOD

SGH SARAWAK 2017

LANCET NEUROLOGY 2002; 1: 101–09

WHEN SHOULD WE SUSPECT HUMAN RABIES ?

1. Clinical manifestations ( Acute meningo-encephalitis or GBS ) + History of Dog/ Cat Bite/ Scratch

2. Clinical manifestations ( Acute meningo-encephalitis or GBS ) with fairly atypical progression without history of dog or cat bite.

HOW TO DIAGNOSE HUMAN RABIES?

Clinical suspicion in patient who presented with GBS or meningo-encephalitis picture.

Good history taking – dog bite, no history of dog bite but from rabies endemic area.

Good clinical examination to look for dog bite marks.

VERY IMPORTANT

Pay attention to the

1. Dog or cat behaviour

2. Time of bite to onset of symptoms

3. Did the patient received PEP and how timely is the PEP.

4. How thorough is the wound washing performed?

WHAT CLINICAL SPECIMENS TO SENT ?

1. Saliva

2. Nuchal biopsy

3. Cerebrospinal fluid ( CSF )

4. Urine

IMR

HUMAN RABIES: LABORATORY CONFIRMATION

One or more of the following:

•Presence of virus antigen

•Isolation of virus in cell culture or in animals laboratory

•Presence of viral-specific antibodies in the cerebrospinal fluid

or the serum of an unvaccinated person; or

•Presence of viral nucleic acids detected by molecular methods

in samples (e.g. brain biopsy, skin, saliva, concentrated urine)

collected post mortem or intra vitam.

Direct Fluoresecent Antibody ( DFA ) or

Immunohistochemistry ( IHC )

SPECIMEN COLLECTION & TRANSPORT

PATIENT MANAGEMENT

When patient is presented with sign and symptoms of rabies, rabies vacciantion or RIG is no longer effective and indicated.

Mortality rate is 99.9%.

POST BITE MANAGEMENT

WHO Prequalified

Vaccine

Purified RIG – Equine

or Human

Improper

Wound

Washing !

PROMPT MANAGEMENT OF WOUND

Good Wound Care :

Can reduce risk of rabies

infection by up to 40-

90%.

PEP

1. Active immunisation : Rabies vaccine ( Non-Neural )

2. Passive immunisation : Rabies immunoglobulin

VERORAB

• PVRV-purified inactivated rabies vaccine, prepared on vero cells

• By Sanofi Pasteur

GENERAL CONSIDERATIONS FOR PEPInitiation of PEP should not await the results of laboratory diagnosis or be delayed by dog observation when rabies is suspected. ( ANIMAL that bite )

PEP may not be required when animal contacts (excluding bats) occur in areas free of carnivore-mediated rabies and where there is adequate surveillance in place. The decision must be based on expert risk assessment.

Patients presenting for rabies PEP even months after having been bitten should be treated as if the contact had recently occurred.

SARAWAK CONTEXT

BASIC DECISION FOR PEP

Basically, decisions are made based on ALL criterias below

Dog characteristics – health and ability to be observed

Wound care at time of bite

Animal rabies vaccination history

Wound category ( 2 or 3 )

CLINICAL FEATURES TO SUGGEST RABIES IN ANIMAL

Sudden change of behaviour – more aggressive, biting other pets in house as well as inanimate objects

Provoked Bites that involved activities with people who are familiar to the pet which usually does not trigger a bite (i.e. bathing, feeding, petting)

Dumb looking

Hypersalivation

Hydrophobic - scared of water ( either taking bath / drinking water )

Walk with unsteady gait, limp or wandering around aimlessly

CLINICAL FEATURES TO SUGGEST RABIES IN ANIMAL

Animal bite has to be forcefully removed

Change in bark / unable to bark or barks softly.

Multiple unprovoked bite sites/attack on the same person

Bite more than 1 person or other animal within the same day

Poor appetite or lethargy

Unprovoked bite of familiar persons

Bite more than 1 person or other animal within 14 days when animal not known to be aggressive in the past

FOR STATE / AREAS WITH NO REPORTED ANIMAL RABIES CASE

In the presence of good surveillance data ( random stray dog sampling ) , PEP can be postponed awaiting dog sampling result if can be made available as soon as possible.

In the absence of good surveillance data and dog sampling result will not be available within next few days, this patient might need PEP ( if clearly the animal that bite has risks and was showing signs and symptoms of possible canine rabies )

1. IPC regimen

-2 doses (0.1 ml) of ID route at each visit

-Day 0, 3 & 7

-All population

2. 4-dose Essen regimen

-1 dose (1 vial) of IM route at each visit

-Day 0, 3, 7 & 14-28

-All population

IMMUNOCOMPROMISED HOST

Patients who are on corticosteroids, other immuno-suppressive agents, chloroquine

Patients who has immunosuppressive illnesses (e.g. congenital immunodeficiency, HIV with CD4 count of <200cells/µL, leukemia, lymphoma, generalized malignancy) may interfere with the antibody response to rabies vaccine.

PRE-EXPOSURE PROPHYLAXIS ( PREP ) REGIME

Intradermal ( ID ) regime :

0.1 ml on each deltoid ( total 0.2mls ) on Day 0 and 7

0.1ml on one deltoid side ( total 0.1ml ) on Day 0, 7 and 21 or 28.

Intramuscular ( IM ) regime :

0.5 mls ( 1 vial ) on one deltoid side on Day 0 and 7

0.5 mls ( 1 vial ) on one deltoid on Day 0, 7 and 21 or 28.

Given 1X only

Not to whom previously have PEP or PrEP

At or ASAP after PEP vaccination

Not > D7 after 1st vaccine dose

Maximum dosage by body weight

hRIG: 20 IU/kg

eRIG: 40 IU/kg

All RIG or as much as possible is given to all wound site(s) only, dilute RIG if needed

Current PEP on RIG use

(WHO 2018)

Prioritization of RIG Rx

probable or confirmed rabid animal

multiple or deep wounds

highly innervated parts: head, neck, hand, genitalia

Immunocompromised

Exposure to bat ( vampire )

WHEN TO GIVE ANTIBIOTIC ?

INSULIN NEEDLE USED

ADVANTAGES OF INTRADERMAL RABIES VACCINE

1. Same efficacy or immunogenicity.

2. Cost effective.

3. Conserve the vaccine supply and made it more readily available.

4. Less painful.

THE BIGGEST CHALLENGE

Manage the available resources ( Vaccine + RIG )

Building capacity to give Intradermal Rabies vaccine.

IN CONCLUSION

1. Rabies in canine and now feline is still rampant in Sarawak.

2. The challenges in diagnosis of human rabies are

Clinician experience and suspicion of the disease - ability to link clinical history and presenting sign and symptoms.

Adequate and appropriate samples are collected. Temperature of keeping the clinical specimen and transporting must be emphasized.

PCR has its limitation. Continous effort must bgoing to improve the sensitivity of the test.

3. Managing available resources is not easy.

Please

Remember!!

You are not

Cesar Millan