11-13: Infectious Disease, Herd immunity, Outbreak Investigation

*What is the relationship between amplifier and essential hosts?*

*Not all amplifier hosts are essential hosts, but all essential hosts are amplifier hosts*

What eventually brought the FMD epidemic in the UK to an end?

*Restriction of movement of farm vehicles.* Practical precautions taken to minimise the risk of an infectious agent being introduced.

What is attack rate and how is it calculated?

Typically used for acute diseases, often in an outbreak situation. = # new cases for epidemic period/population at risk (entire population)

What were the lessons to be learnt from the FMD outbreak in the UK?

UK vets doing inspection at entry ports kept poor records and were inadequately trained to detect foreign animal diseases. Registration procedures for shipments did not fulfill EU regulations. Government must strengthen vet surveillance/tighten import controls to facilitate early detection. Early vaccination may have reduced numbers to be slaughtered (controversial).

How is secondary attack rate calculated?

# new cases (derived from index case)/all those that came into contact with the index case that remained healthy

How is mortality rate calculated?

# of deaths in the population/# of individuals in the total population

What are the criteria used for selection and prioritisation of biological agents?

1) the public health impact. 2) the delivery potential to large populations. 3) potential for person to person transmission. 4) the public perception as related to public fear. 5) the special public health preparedness needs

How many of the emerging infectious diseases (EID) in humans are zoonotic?

75%

How is infectivity calculated?

Animals who become infected/exposed animals in the population

What is the Plum Island Animal Disease Centre (PIADC)?

A US federal research facility dedicated to study of foreign animal diseases. The National Bio and Agro-Defense Facility (NBAF) is a US government-run research facility under the Department of Homeland Security that will replace Plum Island.

What is disease?

A clinically apparent infection - infection accompanied by overt illness. Disease is only *one possible outcome* of infection

What was the major change made by Obama to the HSS and APHIS in 2012?

Addition of tier 1 agents to both, a category that presents the greatest risk of deliberate misuse with the greatest potential for mass casualties/devastation to the economy, infrastructure, or public confidence.

Which kind of dissemination of bioterror agents is the route of greatest concern? Why?

Aerosol: all category A agents can be effectively disseminated via aerosol

What is the period of transmission?

Agent being shed: time during which the host is infectious to others

What is the weaponisation of agents?

Agents typically found in nature, but it is possible that they could be manipulated in a lab to increase their ability to cause disease

What is antigenic shift?

An abrupt, major change to produce a novel virus subtype in humans that was not currently circulating among people

What is a carrier state?

An infected person or animal that harbours an infectious agent. Absence of clinical signs. Sheds the infectious agent so acting as a source of infection to others. *Can last months to years.*

What kind of agents are commonly implicated in intentional attacks? Which are rarely used?

Biological agents commonly implicated. Chemical and radiological agents rarely used.

What is there to note about plague?

Category A agent of zoonotic importance. Yersinia pestis. Owner with cats with pneumonic plague at risk of serious disease

What are the three categories of biological agents prepared by the CDC's bioterrorism preparedness and response office?

Category A: highest priority. Category B: second highest priority. Category C: third highest priority

How do we classify persons/animals as diseased or not diseased?

Clinical signs, immune response, lab detection of agent

What disease parameters are described in the descriptive phase of an outbreak investigation?

Clinical signs: post mortem findings; incubation period; temporal, spatial, demographic patterns; herd history.

What three components of case criteria are variable?

Clinical signs; immunologic response - provides info on start of outbreak; detection of agent (analytical phase) to confirm it is a case

What are clues to occurrence of an intentional event?

Clustering of disease (temporally or geographically, healthy animals or people), disease occurring outside normal season, disease occurs in a different species to the expected, dissemination may cover large area very quickly (airborne), acute morbidity/mortality depending on the agent

What questions should be asked during the initial investigation of an outbreak?

Confirm that an outbreak exists. Is there a true increase in the incidence of disease? What is the disease? Characterise cases to create a formal case definition. May not be possible to make a definitive diagnosis at this stage

What are the major US federal agencies important in veterinary involvement in response to biological disasters?

Department of Homeland Security, the Department of Health and Human Services (HHS), and the US Department of Agriculture's Animal and Plant Health Inspection Service (USDA-APHIS)

What are the stages of the epidemiologic workup in an outbreak investigation?

Descriptive phase, analytical phase, intervention

What is the epidemiologic workup?

Descriptive phase: describe disease parameters: clinical signs, post mortem findings, incubation period, temporal/spatial/demographic. Herd history, case definition, generate epidemic curve. Analytical phase: intervention and control

What were the problems with FMD control measures in the UK outbreak?

Difficult to employ slaughter policy quickly, 1200 overseas vets recruited to assist - Plum Island US vets best trained. Epidemic spread resulting from lack of implementation in certain areas. Public objections to slaughter of infected animals near residential areas. Smoke (pollution, threat to health). Psychological effects (vets, farmers). Outbreaks continue - division amongst vets and government/farmers (need for 'participatory epidemiology').

What causes a carrier state?

Due to incomplete/inappropriate treatment, or poor immune response. The infectious agent is not completely eliminated, leading to carrier state. *Both clinical and subclinical gradients of infection can lead to a carrier state*.

What are consequences of naturally occurring disease and accidental disasters?

Economic devastation, psychological impact, improved preparedness

What makes something a CDC category C agent?

Emerging pathogens that could be engineered for future mass dissemination because of: availability, ease of production + dissemination, potential for high morbidity/mortality major PH impact. *E.g. nipah virus, hantavirus*

What are the disadvantages to vaccinating for FMD?

Existing vaccines: animal left with carrier state and cannot distinguish if antibody produced is from natural exposure or vaccine. Too costly with new vaccine. No one vaccine covers all serotypes and vaccination with one serotype does not confer crossprotection

What are examples of APHIS specific agents that are more likely to be used as an agroterrorism agent?

FMD (highest priority), classical swine fever, newcastle disease, vesicular stomatitis, highly pathogenic avian influenza. In addition, other agents categorised on the CDC A-C used to infect animals.

Who are the targets of agroterrorism?

Farm to dinner table. Crops, water supplies, transportation systems, farm workers/farmers, grainholding facilities.

What occurs during the analytical phase of an outbreak investigation?

Generate a hypothesis: review existing descriptive epidemiological data about a suspected disease if known. Who is at risk? What is the disease? Calculate attack rates.

What is required in order to fully achieve herd immunity?

Global coordination of programs, robust and affordable diagnostic tests, international accreditation mechanism (e.g. OIE), guidelines for surveillance and performance indicators, molecular characterisation of viruses

What makes something a CDC category A agent?

High-priority agents that pose a risk to national security because they can: be easily disseminated/transmitted person to person, high mortality rates and major public health impact, cause panic, and require special action for preparedness. *E.g. anthrax, plague, tularaemia, botulism, small pox (variola major), viral haemorrhagic fever (filoviruses and areanaviruses, e.g. ebola, lassa viruses)*

What are the different modes of transmission?

Horizontal - direct, indirect. Vertical.

What is an amplifier host?

Host in which infectious agent multiplies to high levels sufficient to spread to other hosts.

What is a dead end host?

Host that cannot spread the infection to other susceptible hosts under natural conditions

What are possible outcomes of exposure to an infectious agent?

Immune, clinical infection (disease), subclinical infection, carrier state

What is secondary attack rate?

In animal-animal transmitted infection, quantifies infectivity. It is the probability that infection occurs among susceptible animals following known contact with an index case (primary case)

How is the hypothesis tested during the analytical phase of an outbreak investigation?

In situations where the cause is unknown, to identify the association between exposure, risk factors, and disease using: case-control studies, cohort studies; assess statistical significances

What are emerging, naturally occurring disasters of biological origin?

Incidence has either increased in past two decades or threatened to increase in the near future. E.g. influenza subtypes: pandemic H1N1

What are mechanical vectors?

Indirect horizontal transmission. No replication or development of pathogen in insect vector

What are biological vectors?

Indirect horizontal transmission. Replication or development of pathogen in the vector

What control methods were implimented in the FMD outbreak in the UK?

Infected herds of all species to be slaughtered within 24 hours of detection. Slaughter susceptible animals in contiguous premises by 24-48 hours. Continue surveillance and slaughter of all newly identified infected herds and all susceptibles within the surveillance zone. Stunned then exsanguinated. Carcasses burnt in certain areas. Vaccination considered but not used. Sheep: serosurveillance as clinical signs rare in sheep; infected flocks identified and culled

What are inapparent infections?

Infection of susceptible host but no clinical signs. *Usually* never progress to clinical disease. Demonstration of antibody response by serology is required to show infection is present

What are features of infectious agents and other measures of health?

Infectivity, pathogenicity, virulence, immunogenicity. All influenced by host susceptibility and spontaneous changes within the agents

What is the advantage to vaccinating for FMD?

It can contain the disease if it is used as a preventative measure

How is herd history investigated in the descriptive phase of an outbreak investigation?

Review management records and assess practices. Collect historical, clinical, and productivity data on: those individuals that are affected (cases) and those that are not affected (non-cases)

What is the USDA-APHIS National Vet Services Lab (NVSL)?

Made up for 4 labs which diagnose domestic and foreign animal diseases and have tests for eradication and control programs.

How can herd immunity be acquired?

May be natural, where the agent must be frequently encountered by the herd to ensure a large portion of the herd are exposed and become immune. May be artificially induced (vaccination). Leads to number of susceptibles reduced and number of immune animals dominate the herd.

What makes something a CDC category B agent?

Moderately easy to disseminate. Moderate morbidity, low mortality. Requires enhanced diagnostic capacity and surveillance. *E.g. Brucella, Coxiella burnettii (Q fever), Salmonella, E. coli, Shigella, glanders and melioidosis (Burkholderia), chlamydophila psittaci, rickettsia prowazekii (epidemic typhus fever), encephalitis, toxic syndromes*

Why is agroterrorism so difficult to deal with?

Multiple points of entry, multiple possible delivery methods, natural (accidental) vs. intentional, real vs. hoax

What is more likely a natural/accidental biological disaster or an intentional one (attack)?

Natural/accidental

Does every vaccinated individual become immunised?

No. But the more individuals who do become immune, the more that will resist infection. Need a sufficient % immunised to protect the entire herd.

What is an accidental host?

Not required for maintenance but can become infected with the agent. Does not provide an environment for the agent to multiply/replicate. (but maybe still infective)

What is the vet's role in public health measures?

Not to treat humans, only advise they seek help from their MD. Notify state public health and animal health officials; federal CDC - human cases. Human protection if nursing ill animals - isolation, gloves, mask

What is the select agent program?

Originated as part of the 1996 anti-terrorism act, which directed the secretary of the department of health and human services (HSS) to develop a comprehensive list of biologic agents and toxins. CDC identified agents: causing a severe threat to public health and safety; required *procedures for the transfer* of the listed materials

What is an example of non-emerging, naturally occurring disasters of biological origin?

Plague in parts of the US, FMD in Brazil, Paraguay

What is pathogenicity and how is it calculated?

Proportion of infected people who develop clinical disease. = number infected and exhibiting disease/total number infected

What is virulence and how is it calculated?

Proportion of persons with clinical disease who become severely ill or die. = number with severe disease/total number with disease, OR = fatal cases/total cases (case-fatality rate)

How is relative risk (RR) calculated? How is the result interpreted?

RR = incidence in the exposed/incidence in the unexposed. If RR is close to 1, the exposure is probably not associated with the risk of disease. The greater the departure from 1, the stronger the association. If RR > 1, a positive association (possibly causal). If RR < 1, a negative association (possibly protective)

What is mortality rate?

Refers to the incidence of death among all individuals in the population at risk of developing the disease. Reflects the burden of deaths from the disease in the population as a whole.

What is antigenic drift?

Small, gradual changes that occur through point mutations in the two genes that produce the main surface proteins, haemagglutinin, and neuraminidase. These minor changes account for the annual epidemics.

How does the infectivity of the agent (dose of virus) change?

Spontaneous mutations (antigenic drift/shift), duration of shedding by infected animals and degree of contact between members of the herd. Ease with which the agent is transmitted: airborne FMD rapid spread vs. rabies. Increased population density/movement/travel.

Why would people choose to use the agroterrorism route?

Target isn't really the animal/crops, but the people who rely on them for food and jobs, so it's really economic terrorism. Attacks on plants or animals are less emotionally sensitive than attacks on humans. Often delay in recognision, making getting away easier. Agriculture is a sleeping target, not yet fully recognised for its vulnerability/not yet fully protected.

What is immunogenicity?

The ability of an agent to induce an immune response, as measured by antibody production

What is infectivity and how is it quantified?

The ability of an organism to cause infection in a susceptible host. Infectivity is quantified by the number of infectious particles required to establish an infection

Why don't countries vaccinate for FMD?

The difficulty associated with distinguishing stock exposed to FMD from natural exposure to vaccination - trade implications

What is infection?

The encounter of a potentially pathogenic agent with a susceptible host and the host shows an immunologic response to infection

What is the antiterrorism act?

The first legislation that sought to limit the threat that biological agents or toxins from US research labs would fall into the hands of terrorists

What are reservoirs/essential hosts?

The habitat, either animate or inanimate, in which the infectious agent resides (is maintained) and/or multiplies. Agent is dependent on this reservoir for survival in nature. Infected animal may/may not get disease

What is case-fatality rate?

The incidence of death among individuals who develop the disease. Reflects the prognosis of disease among cases (diseased). Virulence when death is the criterion. The proportion of cases who eventually die from the disease. = # fatal cases/# total cases

What is bioterrorism?

The intent is to threaten people directly with biological organisms. The deliberate release of viruses, bacteria, or other agents used to cause illness or death in people, animals, or plants.

What does the USDA-APHIS do?

The lead federal agency in safeguarding American livestock and poultry health and in responding to an outbreak/attack on animals. The emergency programs (EP) devision prepares and trains federal and state vets, epidemiologists and animal techs for response.

What is agroterrorism?

The malicious use of plant or animal pathogens to cause disease in the agriculture sector. The deliberate introduction of an animal or plant disease with the goal of generating fear over the safety of food, causing economic loss and/or undermining social stability. The intent is to indirectly attack persons by destruction of the plant and animal infrastructure

What is a case definition?

The operational definition of a disease for study purposes and ensures: cases are consistently defined and defines that distinguishes cases from others in the population.

What is herd immunity?

The resistance of a group, community, or population to the introduction and spread of an *infectious disease*, based on the collective immunity of the group. Provides barriers to direct transmission of infection through the herd.

What is infectious disease epidemiology?

The study of the determinants of infectious diseases and the application of this knowledge to prevention and control. An infectious agent is a necessary cause.

What is the incubation period?

The time period between exposure to an agent (infection) and onset of clinical signs/symptoms of disease

What is the latent period?

Time period between the initiation of infection in the host and when the host becomes infectious to others (first shedding of the agent)

What is the chain of infection?

Transmission from a host/reservoir, through a portal of exit, conveyed by some mode of transmission, and enters through an appropriate portal of entry to infect a susceptible host

What is vertical transmission?

Transmission of infection from one generation to the next - infection of embryo, foetus, egg; transmission by colostrum to offspring

What was the disagreement regarding vaccines during the UK outbreak of FMD?

Vets supported vaccination to limit spread but not the farmers/government (carrier status and damage to trade). Small farmers were for vaccination to protect the herds they had created over decades.

When is herd immunity accomplished?

When the number of animals in a given population that have acquired immunity is so great that under natural conditions a contagious agent cannot enter and spread within the herd.

What is primary penumonic plague?

Without treatment, 100% fatal. Develops as a result of inhaling infectious droplets from infected cat or human. Most likely form to be used as a bioterror agent: pneumonic form causes high mortality. Rapidly spread via aerosol transmission.

Is there a FMD vaccine?

Yes. Killed virus, safe for pregnant cows, provides immunity for six months. Vax to match serotype: costly to implement where more than one serotype is involved. Protection from clinical signs, *not* infection.

What are viral haemorrhagic fever (VHF) viruses and how can they be used in bioterrorism?

Zoonotic. Main concern: aerosolised forms of Ebola would be a likely form of use as a bioterrorism agent. No effective treatment or vaccination - targeted population would be uniformly susceptible

What are some good candidates for bioterrorism agents? Why are vets important in this situation?

Zoonotic: B. anthracis, Yersinia pestis, Coxiella burnetii, Francisella tularensis. May appear in animals first. Vets trained to recognise these diseases and vet labs equipped to diagnose them