ANNUAL LECTURE SERIES ON ONE HEALTH APPROACH ON RABIES PREVENTION AND CONTROL

Theses slides are mainly for use in research, study and training for both human nd veterinary professionals, and it was developed on the one health concept

1. NIGERIAN VETERINARY MEDICAL ASSOCIATION (NVMA), ZAMFARA STATE CHAPTER 2022 WORLD RABIES DAY ANNUAL LECTURE SERIES ON RABIES AWARENESS CAMPAIGN TO BE DELIvERED BY Dr . Ibrahim Hassan, DVM, MS c PH, MNIM, FIPMA Resident AT NCDC/FIELD EPIDEMIOLOGY & LABROTORY TRAINING PROGRAM 1

2. 5Ws About World Rabies Day WHAT : A day of declaration, commitment and action on the menace of rabies wherever possible. WHO : International and national human and animal health organizations, human and veterinary public health professionals, non-governmental organizations, World Health Organization, Collaborating Centers, universities, corporate and private partners. WHERE: As many countries as possible (more than150 countries have so far joined). WHY : Raise awareness and enhance prevention and control of this dreaded but neglected disease. WHEN : September 28 th Annually ( www.WorldRabiesDay.org ) 2

3. OBJECTIVES To raise global awareness about rabies. To raise awareness about impact of rabies on human and animal. To provide information and advise on how to prevent the disease in at risk community. To promote education in local communities to control and prevent rabies. To mobilize and coordinate resources towards human rabies prevention and animal rabies control. To support advocacy for increased efforts in rabies prevention and control. ( www.WorldRabiesDay.org ) 3

4. WHY 28 TH SEPTEMBER EVERY YEAR Louis Pasteur(a French biologist, microbiologist and chemist ). He was the first person to diagnose that rabies targets the Central Nervous System ( CNS). On July 6, 1885 he created the rabies vaccine and saved 9 year old Joseph Meister after he had been bitten by a rabid dog. 4 Dec. 27, 1822 to Sept. 28, 1895

5. Since September 2007…… Number of participating countries keeps increasing 150+ participating schools of public health, veterinary and medical colleges have hosted one or more ‘rabies- awareness’ events. New animal vaccination programs in endemic countries. New and invigorated educational programs. Global community networks. Listed on UN website of globally observed health days. Partnership with governments and the Global Alliance for Rabies Control. Additional funds from WHO and other NGOs. 5

6. One Health is a collaborative, multisectoral and transdisciplinary approach, working at the local, regional, national and global levels with the goal of achieving optimal health outcomes recognizing the interconnections between people, animals, plants and their shared environment . What is One Health? One Health Focus Areas Zoonotic and emerging infectious diseases Pandemic preparedness and response One Health emergencies at the human-animal-environment interface Global health security and capacity building Strategic One Health partnerships Prevent zoonoses shared between people and pets etc. 6

7. THEME FOR THE YEAR 2022 WORLD RABIES DAY 7

8. ONE HEALTH CONCEPT: THE CLIMAX OF RABIES PREVENTION AND CONTROL strategies 8

9. 9 ETYMOLOGY The word RABIES originates from the Latin word RABERE & this means t o RAGE or RAVE & may have roots in Sanskrit word RAHABS, which means to do violence. The Greeks called RABIES, Lyssa or Lytta which means FRENZY or MADNESS.

10. WHY IT IS IMPORTANT TO KNOW ABOUT RABIES It is acute viral disease that causes fatal encephalomyelitis in virtually all the warm-blooded animals including man. The disease is inevitably fatal and perhaps the most painful and dreadful of all communicable diseases in which the sick person is tormented at same time with thirst and fear of water (hydrophobia). Till date there is no cure if you developed the disease and death is inevitable. 10

11. What is rabies Rabies is an acute infectious disease characterized by abnormal behaviours, nervous disturbances, ascending paralysis followed by death. It is an acute, progressive, incurable viral encephalitis (inflammation of the brain) that affect man and all warm blooded animals such as Dogs, Skunk, Cats, Jackals , Bats and wolves etc. It is an ancient ( since 3000 B. C.) viral zoonotic disease (disease that is transmitted from animals to humans) that is invariably fatal in humans and mammals . It is caused by neurotropic RNA viruses of the Rhabdoviridae family, genus Lyssavirus. Mammalian reservoirs include the Carnivora ( d ogs , foxes, raccoons, skunks , jackals, mangoose etc ) and Chiroptera ( Insectivorous , hematophagous, and frugivorous bats) Dogs bite mediated rabies still pose the greatest hazard worldwide. A single infected dog is capable of transmitting the disease to over an area of 40 km. Rabies is a 100% vaccine-preventable disease. 11

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13. EPIDEMIOLOGY Globally more than 60,000 people died due to rabies infection annually. > 95% of human death is coursed by dog-mediated rabies.   Worldwide almost half of all rabies death occur in children under 15 yrs. > 95% of human death occur in Africa & Asia.   It is present in all continent except Antarctica. It is a Neglected Tropical Disease (NTD) affecting poor and vulnerable population. It is a threat to more than 3 billion people across the globe. One of the oldest described infectious diseases known for more than 4000 yrs. 13

14. COUNTRIES AT RISK OF RABIES 14

15. GLOBAL BURDEN OF ENDEMIC CANINE RABIES Every year there is 3.7 million DALYS due to canine rabies worldwide. Global total death is 60,000 every year . The annual overall economic cost was estimated at 8.6 billion USD Premature death is 2.27 billion USD Direct expenditure for PEP is 1.70 billion USD Lost of income while seeking for PEP is 1.31 billion USD Livestock death ( in Africa) is 512 million USD Globally over 70% of the estimated economic burden was societal (premature death & losses due seeking for PEP ). 20% goes medical sector/bite victims (direct cost ) More than 8% goes to veterinary sector due to livestock losses (direct to community) Only 0.01% of cost were for Laboratory – based surveillance. 15

16. DIVISION OF COST ASSOCIATED WITH RABIES 16

17. MORPHOLOGY OF CLASSICAL RABIES VIRUS Order :– Mononegavirales Family :– Rhabdoviridae Genus :– Lyssa virus Species :– Classical rabies virus Bullet-shaped (75 x 180 nm) Enveloped Single stranded RNA genome Virus cannot grow unless it is inside a living cell. Has a lipoprotein envelope Knob like spikes or glycoprotein G. Matrix protein layer Genome –unsegmented , linear, negative sense RNA. 17

18. LYSSAVIRUS GENERA Rabies virus (RABV genotype 1) being the most prevalent & worldwide in distribution. Lagos Bat Virus (LBV genotype 2) Mokola Virus (MKV- genotype 3) Duvenhage Virus (DV, genotype 4) European Bat Lyssavirus -1 (EBLV-1 Genotype 5) European Bat Lyssavirus -2 (EBLV-2 genotype 6) Australian Bat Lyssavirus (ABLV, genotype 7) Khujand Virus (KV) Avian Virus (AV) Irkut Virus (IV) West Caucasian Bat Virus (WCBV) Identified in Nigeria in 1950 Identified in South Africa in 1970 NEW GENERA 18

19. MAP OF 7 CONTENENTS AND 5 OCEANS OF THE WORLD 19

20. Global distribution of animals involved in rabies viruses transmission 2

21. MODE OF TRANSMISSION Bite/ scratch that introduces virus-bearing Saliva into the victim’s body and this has 90% chances of developing the infection more than all other route (Fitzpatrick et al., 2012). Direct contact ( viral contamination) such as broken skin or mucous membranes in the eyes, nose or mouth with saliva or brain/nervous system tissue from an infected animal. Organ transplantation ( very rare). Aerosol of rabies virus ( especially for lab. Workers). Ingestion of the virus. 2 1

22. DAYNAMICS OF RABIES VIRUS TRANSMISSION AND EXPOSURE 2 2 DEAD-END HOST

23. DAYNAMICS OF RABIES VIRUS TRANSMISSION CONT……. 2 3

24. NOTE Man remains the dead-end host, as he can’t transmit the disease to his fellow human being or animal. 2 4

25. INCUBATION PERIOD This is the period from the time of exposure up to the appearance of first clinical signs and symptoms of rabies . It has high variability, usually 3 to 8 weeks in some cases. It may be from 2 weeks to 6yrs, with an average of 2 to 3 months. It maybe be within 4 days or maybe prolonged for years. The variability in the incubation period also depends on ; Concentration of the viral load contained in the saliva Site of the bite or scratches innervation density of the site Severity of the bite Number of wound Presence/absence of appropriate treatment and PEP protocols 2 5

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27. After inoculation, the rabies virus multiplies in the muscle cells (myocytes or may invade the nerve directly without prior multiplication in the myocytes. The virus then penetrates the peripheral nerve cells via viral uptake at neuronal endings and then transported through both the sensory and motor nerve fibers to the central nervous system (CNS). Once the virus reaches the CNS, rabies replication occurs primarily in the neurons or brain cells through viral budding and the virus spreads and infects the nearby brain cells . While viral dissemination occurs in the central nervous system, the rabies virus spreads into the peripheral tissues such as muscle fibres, salivary glands, corneas, adrenal medullae, lacrimal glands, myocardium, kidneys, lungs, pancreas and epidermis. Infection of salivary glands allows further transmission of the disease to other mammals . 27

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30. PATHOGENESIS CONT…… 30

31. CLINICAL STAGES OF RABIES 31

32. CLINICAL STAGES IN MAN Prodromal stage (Non specific sign/symptoms) occurs when there is initial viral replication at the striated muscle cells at the site of inoculation just before it enters the brain . Headache Malaise Sore throat Slight fever Nausea Vomiting Anorexia Abdominal pain Paraesthesia 3 2 THIS STAGE LAST FROM 0 – 10 DAYS OR 2 WEEKS

33. Acute Neurological Stage: This is when the virus reaches the CNS and replicates especially in the gray matter. It has two types of presentation Encephalitic or furious type, which has 80% of cases and paralytic or dumb type, which is seen in 20 % of cases. This stage last for 2 – 7 days Encephalitic or Furious Rabies Excessive motor activity, Excitation ,Agitation Confusion, Hallucinations, Delirium Hypersalivation, Aphasia, Pharyngeal Spasms Hydrophobia or Aerophobia (50 -70% ) Incoordination, Hyperactivity , Lacrimation , Salivation & Perspiration Seizures , Muscle spasms, Meningism, Opisthotonic posturing paralytic or dumb Rabies Acute progressive ascending myelitis symmetrical or asymmetrical flaccid paralysis pain and fasciculation in the affected muscles with mild sensory disturbance. A complete paraplegia develops eventually with fatal paralysis of the respiratory and pharyngeal muscles . 3 3

34. 3 4 Furious Rabies Paralytic Rabies

35. COMA STAGE: This is the progression of stages mentioned earlier and is associated with multi-organ failure, especially Haematemesis and Cardiac arrhythmias seen among 30-60 % of patients. DEATH STAGE: This occur following cardiac and circulatory insufficiency with myocarditis, cardiac arrhythmia or congestive heart failure. Once the clinical sign/symptoms sets in, chances of dying is 99.999%. 3 5

36. CLINICAL STAGES IN DOG INCUBATION PERIOD: Ranges from 3-8 weeks but it may be as short as 10 days or as long as 1 year . Loses its fear of people , aggression. Bites unusual objects- stick , straw and mud (pica appetite) Tendency to run away from home and wander . Barks and growls in a hoarse voice or unable to bark. Excessive & Foamy salivation at the angle of Mouth. Later stage paralysis of the whole body leading to coma and death. Exciting and irritating stage is lacking . Its predominantly paralytic. Dog withdraws from being seen and disturbed . Elapses into stage of sleepiness and dies. Dies in about 3 days . ENCEPHALITIC OR FURIOUS RABIES PARALYTIC OR DUMB RABIES 3 6

37. FURIOUS RABIES DUMB RABIES 3 7

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39. DIAGNOSIS IN HUMANS Laboratory diagnosis of rabies is often based on the following: Clinical manifestations History of exposure to rabid animal NOTE: In cases where pathognomonic signs (Hydrophobia &/or Aerophobia) are present diagnosis is straight forward. Clinical diagnosis may be difficult in paralytic rabies (Atypical presentation). Laboratory confirmation is necessary. N o single test is sufficient 39

40. DIAGNOSIS CONT……. Array of lab sample required for Rabies diagnosis: Saliva CSF Tears Serum INTRA VITAM Urine Skin biopsy ( ( Dachex et al., Plos NTD, 2010) Array of lab tests required for Rabies diagnosis : Fluorescent Antibody Testing (FA), it is gold standard test for rabies Dx . (AM) P olymerase Chain Reaction (PCR), it is extremely efficient & sensitive Serology Histology, to identify negri bodies, which are round cytoplasmic inclusion bodies. (gold standard for PM). 4 Samples for post-mortem diagnosis includes brain tissue that can be collected through trans-orbital or trans-foramen magnum route if autopsy cannot be performed .

41. DIAGNOSIS IN DOGS DIRECT FLUROSCENT ANTIBODY TEST (DFAT): Highly reliable and best single test for rabies antigen detection . It is gold standard test approved by both World Health Organization (WHO) and World Organization for Animal Health (OIE). MICROSCOPIC EXAINATION: This is histopathological test conducted at post mortem, it identifys negri bodies bodies in 75-90 % of cases . 4 1 In 1903, Negri, an Italian scientist demonstrated the viral particles as cytoplasmic inclusion bodies in the Neurones of the rabid Animal, now named after him as NEGRI BODIES

42. Case management of rabies patient Once the sign and symptoms sets in, attention should be centred on comfort care as there is no specific treatment so far, and it include sedation, avoidance of intubation and life support measures. 1. MEDICATION Diazepam Midazolam Haloperidol + Diphenhydramine 2. SUPPORTIVE CARE Patient with confirmed rabies case should receive in an appropriate medical facility Intensive therapy in the form of respiratory and cardiac Support Ensure hydration and diuresis Provide suitable emotional and physical support Honest and gentile discussion concerning prognosis should be provided to the relatives of the patient . 42

43. Case management cont.…… 3. INFECTION CONTROL Patient should be admitted in a quiet, draft-free, isolation room Health care workers and relatives in contact with the patient should wear proper PPE (gown, gloves, mask, goggles). 4 3

44. RABIES PREVENTION AND CONTROL 4 4

45. DEFINITIONS OF TERMS PREVENTION: This: is the management of those factors that could lead to disease or a negative health outcome in order to halt the occurrence of that disease or negative health outcome in a population. CONTROL: Is the reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a result of deliberate efforts, continued intervention measures which are designed in order to maintain the reduction. PREVENTION & CONTROL PROGRAM: Is a set of policies, plans and guidelines that form a comprehensive strategy in order to prevent and control infectious diseases. 4 5

46. CONPONENT OF RABIES PREVENTION AND CONTROL Generally this has two components viz : Animal Rabies Control Human Rabies Prevention NOTE: Disease can be controlled and prevented by adequate measures which include Diagnosis Investigation Notification Disinfection Isolation Blocking of transmission Treatment Immunization Quarantine Health education 46

47. ELEMENT OF HUMAN RABIES PREVENTION 1. Avoiding Exposure i.e. Avoiding contact with unknown animals Nursing rabid human/animal with extreme precaution 2. Pre-Exposure Prophylaxis (PrEP): This is a series of Human anti- rabies vaccines recommended for anyone who is at continual, frequent or increased risk for exposure to the rabies virus such as laboratory workers, veterinarians and animal handlers. 3. Post- Exposure Prophylaxis (PEP): This is an anti- rabies vaccine administered to anyone after an exposure to a confirmed or suspected rabies virus. 4. Post-exposure treatment of persons who have been vaccinated previously. 47

48. FIRST AID FOLLOWING ANIMAL BITE Wound should be washed immediately with soap and running water for about 10 minutes. Wound should be clean thoroughly with 70% alcohol, or povidines iodine. Next visit the hospital/health facility to receive specialized treatment such as Anti tetanus immunization when necessary . Antimicrobials should be prescribed if necessary to control bacterial infections. 48

49. PATIENT SCREENING Patient Screening Categorization of the exposure Major exposure or Minor exposure 49 Before the decision for PET is made

50. MAJOR EXPOSURES Single or multiple bites with bleeding on head, face, neck, chest, upper arms, palms, tips of fingers and toes and genitalia. Multiple scratches with bleeding on head, neck and face. Single or multiple deep bites on any part of the body. Contamination of mucus membranes with saliva. Bites of wild animals with bleeding. 5

51. MINOR EXPOSURES  Single , superficial bite or scratch with oozing of blood or scratches with bleeding on the lower limb , abdomen and back.  Nibbling of uncovered skin.  Contamination of open wounds with saliva.  Multiple bites without bleeding or scratches with oozing of blood on any part of the body.  Drinking raw milk of rabid cow or goat.  Superficial bites and scratches of wild animal without bleeding. 5 1

52. ANIMAL SCREENING Healthy or sick Vaccinated or unvaccinated Observable or unobservable 5 2

53. ANIMAL SCREENING cont.…. Healthy means : The behaviors of the animal is normal Bitten under provocation (provoked bite) Not Healthy means: Animal behaviors not normal Presence of any suspected symptoms/signs Unobservable means: Animal dead, killed, missing, stray or wild animal Observable means: Animal should be put in a cage or Leashed 5 3

54. ANIMAL SCREENING cont .…. Vaccinated means : The status of the animal before the bite incidence. 1. Should have minimum of 2 Rabies vaccinations, given not more than 2 years apart, last vaccination given is within 1 year of the Incident. Bite from animal of this status is termed as major exposure. 2. Has a minimum of 1 vaccination and the last vaccination given within 1 year of the incident. Bite from animal with such kind of vaccination status is termed as minor exposure. NOTE: 54 vaccination of animal especially dogs and cats is annual .

55. SCHEMATIC DIAGRAM FOR PEP INDICATION 5 5 PATIENT SCREENING MAJOR MINOR A NIMAL SCREENING HEALTHY, VACCINATED & OBSERVABLE SUSPECIOUS,SICK OR UNVACCINATED OBSERVABLE LAB CONFIRM OR UNOBSERVABLE HEALTHY, VACCINATED & OBSERVABLE SUSPECIOUS,SICK OR UNVACCINATED OBSERVABLE LAB CONFIRM OR UNOBSERVABLE Delay Observe 14 PEP SUSPENDED Initiate PEP Observe 14 d Discontinue ± Initiate PEP Continue full course Delay Observe 14 PEP SUSPENDED Initiate PEP Observe 14 d Discontinue ± Initiate PEP Continue full Course

56. If PEP is indicated: Major category Immunoglobulin ( RIG) and Anti Rabies vaccine (ARV) Minor category Anti Rabies vaccine (ARV ) 56 IMMUNOGLOBULINS ANTI RABIES VACCINE

57. Intramuscular administration of vaccine for PEP Essen regimen : The 5-dose regimen prescribes 1 dose on each of day 0, 3, 7, 14, and 28. DOSE: one IM dose (1.0 or 0.5 ml) into deltoid (or thigh ) DAY: 0 3 7 14 28 HUMAN RABIES IMMUNOGLOBULINS HUMAN ANTI RABIES VACCINE 57

58. Im administration of vaccine for PEP CONT…. Zagreb regimen: The 4-dose abbreviated multisite regimen prescribes 2 doses on day 0 (1 in each of the 2 deltoid or thigh sites ) followed by 1 dose on each of days 7 and 21, as shown below. DOSE: one IM dose (1.0 or 0.5 ml) into deltoid (or thigh ) Day: 0 7 21 Sites: X2 Xl Xl HUMAN RABIES IMMUNOGLOBULIN HUMAN ARV 58

59. INTRADERMAL ADMINISTRATION FOR PEP The 2-site regimen prescribes injection of 0.1 ml at 2 sites (deltoid or thigh) on days 0, 3, 7 and 28. The day 14 dose is missed. 2-site intradermal regimen ( 2+2+2+0+2) Dose : one ID dose is one fifth of IM dose (0.1 ml) ID per site Day: 0 3 7 28 Sites: X2 X2 X2 X2 IMMUNOGLOBULIN ARV 59

60. Post-exposure prophylaxis for previously vaccinated individuals For rabies-exposed patients who can document previous complete pre-exposure vaccination or complete post exposure prophylaxis with human anti rabies vaccine, 1 dose delivered intramuscularly or delivered intradermally on days 0 and 3 is sufficient. 6

61. Immunization of immunocompromised individuals In immunocompromised individuals including patients with HIV/AIDS, a complete series of 5 doses of intramuscular CCEEV in combination with comprehensive wound management and local infiltration with human rabies immunoglobulin is required for patients with category II and III exposures. 6 1 Pre-exposure prophylaxis IM or 0.1 ml ID on days 0, 7 and either day 21 or 28 is recommended for clinicians and persons attending to human rabies cases, veterinarians, animal handlers

62. ELEMENT OF ANIMAL RABIES CONTROL 1. Mass vaccination of dogs. 2. Movement restriction /confinement. 3. Inter-sectoral collaboration and coordination. 4. Comprehensive surveillance system. 5 . Community Health education and participation 6 . Legal enactment ( dog ordinance and dog registration act.) 6 2

63. MASS VACCINATION OF DOGS Immunize of all dogs ( domestic and community dogs) through mass vaccination campaigns to achieve adequate coverage. Need over 70 % - 80% coverage to get Heard immunity Elimination of stray dogs and ownerless dogs. Immediate destruction of dogs/cats bitten by rabied animals. Pre-exposure prophylaxis of all pet dogs, with booster dose at an appropriate interval. 63

64. Movement restriction /confinement Restrain of dogs in public places Effective DPM programs. Registration and licensing of all domestic dogs. Strong environmental policies/measure against indiscriminate garbage disposal which stimulate the uncontrolled movement of dogs. Quarantine for 6 month of all imported dogs/cats. 64

65. ONE HEALTH APPROACH ON RABIES PREVENTION AND CONTROL GOVERNMENT ENVIRONMENTAL HEALTH SECTORS HUMAN HEALTH SECTOR ANIMAL HEALTH SECTOR WILD LIFE SECTOR NON GOVERNMENTAL ORGANIZATION OTHER SECTORS 65 RABIES PREVENTION AND CONTROL Develop a pilot or Research project

66. CONCEPTUAL FRAMEWORK ON HOW TO PREVENT HUMAN RABIES . 66

67. RABIES ELIMINATION target IN AFRICA/NIGERIA by the year 2030: A REALITY OR A MIRRAGE ???? POINT OF DISCUSSION & CONCERN 67

68. 68 Initial stage

69. ACTION PLAN FOR RABIES ELIMINATION BY THE YEAR 2030 IN NEPAL 69

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