W7:Zoonotic Epidemiology and Canine Rabies

Wildlife Management Approaches in Zoonotic Epidemiology

  • Managing wildlife populations is a critical component of controlling zoonotic diseases. Strategies are broadly categorized into lethal and non-lethal approaches.

  • Lethal Approaches (Culling):  

    • Culling is a widespread method for controlling pests in non-disease contexts and is frequently applied to disease management despite known limitations.

    • Proactive Culling: This involves reducing the size of the host or vector population before disease transmission occurs. It relies on the major assumption that disease transmission is density-dependent.

    • Reactive Culling: This occurs after disease transmission has already been detected. The goal is to limit further spread. For example, it was used in managing foot-and-mouth disease to create a cordon sanitaire.

    • Selective Culling: This involves the removal of specific infected animals (ideally before they become infectious) to reduce transmission. This method requires highly effective surveillance and monitoring systems. It is commonly used to manage bovine tuberculosis in cattle.

  • Non-lethal Approaches:

    • Surveillance: Monitoring populations to track disease presence and prevalence.

    • Spatial Separation: Physically separating wildlife from livestock or human populations.

    • Temporal Separation: Managing interactions based on time to avoid contact during high-risk periods.

    • Veterinary Medicines: Providing direct treatment to wildlife where possible.    

    • Vaccines: Administering vaccines to wildlife or domestic host populations to create immunity.

Virology and Classification of Rabies

  • Rabies is considered a "modern-day success story" in public health, though its management varies significantly between developed and developing nations. Much of its manageable nature stems from it being a "simple" disease.

  • Nomenclature and Classification (Committee for the Taxonomy of Viruses):

    • Order: Mononegavirales  

    • Family: Rhabdoviridae  

    • Genus: Lyssavirus

    • There are currently 14 recognized species within the genus.

  • Viral Structure and Replication:

    • Rabies is a single-strand, negative-sense RNA virus. The RNA is the "antisense" strand, meaning it does not code for messenger RNA (mRNA) directly.

    • Mechanism: The virus hijacks the host's replication machinery to transcribe antisense (negative) RNA into sense (positive) RNA. This positive RNA is then transcribed into mRNA, which is translated into proteins.

    • Genome Characteristics: The RNA is approximately 12 kilobases12\,kilobases long and contains only 5 genes.

    • The five viral proteins coded are:  

      • 1. Nucleoprotein (N)        

      • 2. Phosphoprotein (P)        

      • 3. Matrix protein (M)       

      •  4. Glycoprotein (G)       

      • 5. Polymerase (L)

Taxonomic Diversity of Lyssaviruses

  • Most rabies species have an evolutionary history linked to bats. While European bat lyssaviruses exist in the UK, they are rare (fewer than 30 positive cases in over 15,000 animals tested in species like Daubenton’s bat and Serotine bat).

  • Lyssavirus Species, Hosts, and Locations:

    • Aravan virus: Primary host: Insectivorous bats (Myotis blythi); Location: Central Asia.  

    • Australian bat lyssavirus: Primary host: Frugivorous and insectivorous bats; Location: Australia.  

    • Bokeloh bat lyssavirus: Primary host: Insectivorous bats (Myotis naterreri); Location: Europe?.

    • Duvenhage virus: Primary host: Insectivorous bats; Location: Southern Africa

    • European bat lyssavirus 1: Primary host: Insectivorous bats (Eptesicus serotinus); Location: Europe.  

    • European bat lyssavirus 2: Primary host: Insectivorous bats (Myotis daubentonii, Myotis dasycneme); Location: Europe.

    • Ikoma lyssavirus: Primary host: Unknown (isolated from civet); Location: Africa?.     -

    • Irkut virus: Primary host: Insectivorous bats (Murina leucogaster); Location: East Siberia.  

    • Khujand virus: Primary host: Insectivorous bats (Myotis mystacinus); Location: Central Asia.

    • Lagos bat virus: Primary host: Frugivorous bats; Location: Africa.

    • Mokola virus: Primary host: Unknown (isolated from cats and small mammals); Location: Sub-Saharan Africa.

    • Shimoni bat virus: Primary host: Commerson’s leaf-nosed bat; Location: East Africa.

    • West Caucasian bat virus: Primary host: Insectivorous bats (Miniopterus schreibersi); Location: Europe.

    • Rabies virus (Type species): Primary host: Carnivores (worldwide) and bats (Americas); Location: Worldwide.

Epidemiology and Transmission Cycles

  • Transmission Categories:

    • Canine Rabies: Dogs are the primary host. Humans are secondary or "dead-end" hosts (they do not transmit the disease further).

    • Sylvatic Rabies: Wildlife species are the primary hosts. Secondary (dead-end) hosts include livestock and humans, though other wildlife can also be infected.

    • Bat Rabies: Vampire bats are the primary host. Humans and livestock serve as secondary (dead-end) hosts.

  • Incubation and Infectious Periods:

    • Rabies is characterized by a highly variable incubation period but a very short infectious period.

    • In Dogs: Incubation is typically 2−16 weeks2-16\,weeks (range: 5−10 days5-10\,days up to 1 year1\,year). The infectious period is typically less than 5 days5\,days (maximum 10 days10\,days).

    • In Humans: Incubation is typically 2−12 weeks2-12\,weeks (range: 4 days4\,days up to 6 years6\,years). The infectious period is not applicable as humans are dead-end hosts.

  • Factors Influencing Incubation Period:

    • Type/strain of the virus.

    • Severity of the bite.  

    • Amount of virus injected.

    • Immune status of the host.

    • Proximity of the bite to the brain (e.g., children are often bitten near the head, leading to shorter incubation).

  • Routes of Infection:

    • Primary: Bites from infected animals (mostly carnivores).   

    • Rare: Oral inhalation.

    • Very Rare: Organ donation.

Clinical Presentation and Prognosis

  • Two Clinical Forms:  

    • Encephalitic ("Furious") Form: Characterized by increased aggression. Humans typically present with this form.

    • Paralytic ("Dumb") Form: Characterized by paralysis and reduced aggression.

    • An individual may progress from the furious to the dumb form.

  • Symptoms in Humans:

    • Approximately 80%80\% exhibit hydrophobia (fear of water).

    • Hypersalivation, agitation, hallucinations/delirium, muscle weakness, and coma.

    • 50,000-60,000 deaths annually. 95% in Africa and Asia

  • Prognosis:

    • Death usually results from respiratory failure.

    • Historically, rabies had a 100%100\% mortality rate once symptoms appeared, making it the most lethal disease in the world.

    • There are approximately 4-5 known cases of natural recovery. A study by Gilbert et al. (2012) found that 11%11\% of villagers in a specific Peruvian region had antibodies to bat rabies, suggesting some level of natural exposure survival.

History of Rabies Treatment and the Milwaukee Protocol

  • Louis Pasteur's Contributions:

    • 1879: Developed a vaccine for chicken cholera and starts to investigate rabies.

    • 1881: Performed vaccine experiments against anthrax.

    • 1885: Successfully treated 9-year-old Joseph Meister for rabies using a vaccine, despite Pasteur not being a medical doctor.

    • 1886: Presented a paper on the treatment of over 350 patients using post-exposure vaccination.

  • Modern Post-Exposure Prophylaxis (PEP):

    • Immediate administration of rabies immunoglobulin.

    • A course of vaccinations. Unvaccinated individuals require five injections (days 0, 3, 7, 14, and 30). Previously vaccinated individuals require two (day 0 and days 3-7).

    • Multiple clinic visits are a significant obstacle in developing nations.

  • The Milwaukee Protocol:

    • Developed by Rodney Willoughby in 2004 to treat Jeanna Giese after a bat bite.

    • The patient was placed in an induced coma to protect the brain from dysfunction while the immune system produced antibodies.

    • While Jeanna Giese survived and graduated in Biology in 2011, the protocol has only been successful in about 6 out of 40 cases, possibly depending on the viral strain or the patient's genetics.

Mathematics of Management: The Reproductive Number (R0R_0)

  • Definition of R0R_0: The mean number of secondary cases one case will generate over its infectious period.

    • If R0=1R_0 = 1, the disease is stable.  

    • If R_0 > 1, the disease will spread.  

    • If R_0 < 1, the disease will not spread and will eventually die out.

  • Hampson et al. (2009) Case Study (Tanzania):  

    • Tracked rabies in the Serengeti and Ngorongoro Districts (2002-2007).

    • On average, a rabid dog bit 2.152.15 other dogs (varied up to 22).

    • Probability of a bitten dog developing rabies was 0.490.49.

    • Estimated R0=2.15×0.49=1.05R_0 = 2.15 \times 0.49 = 1.05.  

    • Region-specific R0R_0 estimates: Serengeti = 1.1−1.21.1-1.2; Ngorongoro = 1.1−1.31.1-1.3.

  • Global R0R_0 Estimates:

    • Most values fall between 1.01.0 and 1.71.7, indicating that dog populations are often close to the threshold for management success. This implies that only a small reduction in transmission is needed to eliminate the disease.     - Selected Global R0R_0 Data:

    • Japan (1948): 1.051.05  

    • Tanzania (2003, Rural): 1.141.14  

    • USA (1944, Rural): 1.321.32

    • Kenya (1992, Rural): 1.721.72

    • Mexico (1987, Urban):1.681.68

Canine Rabies Control Strategies

  • Culling Limitations:

    • Culling dogs (reactive or proactive) is often ineffective and socially unacceptable (e.g., proactive culling before the 2008 Beijing Olympics).

    • Social Perturbation: Culling disrupts the social hierarchy and established order of an animal population. This disruption increases fighting and aggression, which facilitates disease spread—the opposite of the intended effect.

  • Vaccination Campaigns:

    • Vaccination is the most effective tool. While coverage of 20−40%20-40\% can theoretically be effective, it often fails at these levels due to population dynamics. A target of over 60%60\% is generally required.

    • Barriers to Success:

      • 1. Cost: Charging for vaccinations significantly lowers coverage. For example, in Tanzania (2003), charged clinics reached 9%9\% coverage, while free clinics reached 64−80%64-80\%.

      •  2. Population Turnover: Coverage decreases over time because people move (taking vaccinated dogs or bringing unvaccinated ones), dogs die and are replaced by unvaccinated ones, and new susceptible puppies are born.

  • Public Health Impact and Goals:

    • Rabies causes an estimated 50,000−60,00050,000 - 60,000 human deaths annually, with 95%95\% in Asia and Africa.

    • Comparative burden (DALYs - Disability-Adjusted Life Years): Rabies DALYs dropped from 3,234,0003,234,000 in 1990 to 1,462,0001,462,000 in 2010.  

    • WHO Target: "Zero human rabies deaths by 2030." This focuses on the fact that 99%99\% of human cases result from dog bites and the disease is 100%100\% vaccine-preventable.