Unit #2 Infectious Disease - Malaria Case Study and Vaccines

"Germs" such as Legionnaires’ Disease, TSS and SARS are...

Parasites

How species effect each other in terms of growth & survival

Species Interaction

Neutral

Neither species affects the other

Competition

Both species negatively affected

Mutualism

Both species benefit

Commensalism

One species benefits, one is unaffected

Parasitism

One species benefits, one species is harmed

Types of parasites

Microparasites + Macroparasites

What happens when a host is exposed to a parasite?

Chain of Infection

Reservoir

Where an infectious agent normally lives, grows, and/or multiplies (could be human, animal or abiotic). Examples: bats that carry ebola, contaminated water

Portals of Entry

Openings in the body that allow the parasite access to the body's tissues. Examples: nostrils -> mucous membranes, wounds -> blood stream

Modes of Transmission

How the virus moves from host to host

Portals of Exit

Openings in the body that the parasite exits through. Examples: nostrils -> snot, urinary tract -> urea

Susceptible Host

Hosts vary in their likelihood of getting infected – some are more resistant (i.e. less susceptible) than others. Examples: The elderly, the very young, pregnant women, etc.

Infectious Agents

Parasites/pathogens Examples: Virus, bacteria, protists

Herd Immunity

Resistance of an entire community to infectious disease due to the immunity of a large proportion of individuals in that community to the disease -Immunized means people have protective immune response due to: 1. Vaccination 2. Prior exposure & recovery

5 species of malaria Plasmodium that infect humans

Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi

What cells do Malaria parasites infect?

Enter through mosquito bite -> liver cells -> blood -> blood cells -> Exit through mosquito ingesting gametocytes

The Human Liver

-Many metabolic & regulatory functions: • Makes bile to solubilize fats in small intestine during digestion • Makes proteins for blood plasma • Makes cholesterol & other special proteins to help carry fats through the body • Stores & releases glucose as needed • Processes hemoglobin to re-use its iron content (liver stores iron) • Converts harmful ammonia to urea (urea is one of end products of protein metabolism that is excreted in urine) • Clears blood of medicines & other harmful substances • Produces proteins involved in blood clotting • Fights infections by making immune factors & removing bacteria from bloodstream • Clearance of bilirubin from breakdown of RBCs -Largest gland/organ in body

Red blood cells (erythrocytes)

-Average life span of 100-120 days -Then broken down & recycled in liver & spleen by phagocytic macrophages

Red blood cells function + hemoglobin

-Specialized cells that circulate through body delivering oxygen (O2) to cells • Also transports carbon dioxide (CO2) • Red coloring of blood comes from iron- containing protein hemoglobin • After water, RBCs are 97% hemoglobin

RBC Gas Transport

-Small size & large surface area of RBCs allows for rapid diffusion of oxygen & carbon dioxide across plasma membrane -In lungs, carbon dioxide is released & oxygen is taken in by blood -In tissues, oxygen is released from blood and carbon dioxide is bound for transport back to lungs

RBC Gas Transport

-Small size & large surface area of RBCs allows for rapid diffusion of oxygen & carbon dioxide across plasma membrane -In lungs, carbon dioxide is released & oxygen is taken in by blood -In tissues, oxygen is released from blood and carbon dioxide is bound for transport back to lungs

Clinical Symptoms of Malaria

-Pathology due to parasite asexual reproduction in RBCs • Why? • Parasite proteins & waste enter blood when infected RBCs burst • Body responds with inflammation • Fewer RBCs to do work

What happens if too many RBCs are destroyed?

Plasmodium parasites can infect & destroy significant number of circulating blood cells, leading to severe anemia

Clinical Symptoms of Malaria

-Pathology due to parasite asexual reproduction in RBCs • Two forms of malaria: 1. Uncomplicated 2. Severe

Uncomplicated Malaria

• Fever and/or chills • Sweats • Headaches • Nausea & vomiting • Body aches • General malaise • Enlarged liver or spleen • Mild jaundice • Increased respiratory rate

Severe Malaria

• Cerebral: impairment of consciousness, seizures, coma • Severe anemia • Hemoglobin in urine • Acute respiratory distress syndrome • Abnormal blood coagulation • Low blood pressure • >5% RBCs infected • High blood acidity • Low blood glucose levels • Organ failure

How does malaria cause fevers in the human body?

• Fever coincides with cycles of RBCs being destroyed by parasite release

Diagnosis of Malaria

Observing parasites in blood, for example by making blood smear and staining:

Demonstration of parasites in blood, for example by making blood smear and staining:

Diagnosis of Malaria

-Can look in blood for: parasite proteins, parasite DNA, or human antibodies against the parasite -Example: Rapid Diagnostic Test (RDT) to detect specific malaria parasites proteins in a person’s blood Get results in 15 minutes

Incubation period

Time between infection by parasite and onset of symptoms

Incubation Period

For malaria: generally between 7 and 30 days depending on what species and strain of Plasmodium

Where does malaria occur?

-In Tropical and Subtropical Regions of the world -Malaria transmission in 91 countries & territories -About half of world’s population lives in area with malaria transmission

What’s so special about Tropical and Subtropical Regions?

-Those regions have right mix of climate and ecology (e.g. temperature, humidity, rainfall, insect & human population density) -Vector of malaria is the Anopheles mosquito, which can survive & reproduce in these regions -Malaria parasites can grow & develop in mosquitoes in these regions -At temps below 68F, Plasmodium falciparum cannot complete growth cycle in mosquitos

Why is Africa most affected by malaria?

1. Very efficient disease vector is present (Anopheles gambiae) 2. Highly virulent malaria species (Plasmodium falciparum) is present 3. Local weather conditions allow transmission to occur all year 4. Relatively fewer resources for prevention & treatment 5. Economic and political instability impacts control efforts

How many cases and deaths result?

In 2007: -Estimated 219 million cases [estimate range: 203-262 million] -435,000 deaths worldwide

Who is most vulnerable?

Most vulnerable are those with little or no immunity against disease 1. Young children 2. Pregnant women 3. Travelers or migrants from areas with little or no malaria transmission ~61% of deaths due to malaria are in children under 5 years of age

What are the social and economic costs?

-Direct costs = at least $12 billion dollars per year -Costs to individuals and families = ? -Costs to countries = ?

How can incidence of malaria be reduced?

History of anti-Malaria Efforts in U.S.

• 1914 - First funding to US Public Health Service to control malaria in US • 1933 - Tennessee Valley Authority created to develop Tennessee River’s hydroelectric power & improve land and waterways • Malaria affected 30% of population in area in 1933 • By 1947, disease was essentially eliminated by controlling the mosquito vector • 1947 - Start of National Malaria Eradication Program (NMEP) • Cooperative effort in 13 Southeastern states and CDC with annual budget of ~$1 million • >4.6 million homes (interior surfaces of rural homes mostly) & many county areas sprayed with insecticide DDT (dichloro-diphenyl-trichloroethane) • Additional activities: wetland drainage and removal of mosquito breeding sites • RESULT: 15,000 malaria cases in 1947, but only 2,000 by 1950 • 1951 - Malaria in the U.S. is no longer considered a public health concern

Current Status of Malaria in U.S.

How many malaria cases are reported in US every year? Answer: ~1,500-2,000 cases per year in US Where do they occur? What is the source? • Most US malaria infections in people who have traveled to regions with ongoing malaria transmission • Occasionally acquired by people who have not traveled out of US through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquito-borne transmission

Vector

Organism that can carry infectious agents (such as viruses, bacteria, protozoa, worms) from one host to another host or from a reservoir to a host

Biological vector

-Vector that takes up infectious agent, usually through blood meal from an infected host. Infectious agent replicates and/or develops in vector and is transferred to new host through vector bite. -Examples include: mosquitoes, ticks, fleas, mites, some biting flies, lice

Mechanical vector

- Vector that physically transports infectious agent from source to a susceptible host. Passive transfer; infectious agent does not replicate or develop in/on the vector. -Examples include: house flies & cockroaches

Vector-borne disease trends in United States

-Cases of tick-borne diseases doubled from 2004-2016 -Cases of mosquito-borne diseases varied, but were punctuated by epidemics -Lyme disease accounted for 84% of cumulative tick-borne diseases

Lyme Disease

-Caused by bacterium Borrelia burgdorferi (and rarely, Borrelia mayonii) -Transmitted to humans through the bite of infected blacklegged ticks • Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans • If left untreated, infection can spread to joints, heart, & nervous system • Lyme disease is diagnosed based on symptoms, physical findings (e.g., rash), and possibility of exposure to infected ticks

Erythema migrans

Bulls eye rash caused by Lyme disease

Changes in Lyme Disease Case Reports (2001-2014)

Reports have increased in the U.S. over time

Laboratory criteria for diagnosis

Laboratory Criteria for Diagnosis: 1. A positive culture for B. burgdorferi, OR 2. A positive two-tier test. • This is defined as a positive or equivocal enzyme immunoassay or immunofluorescent assay followed by a positive Immunoglobulin M1 (IgM) or Immunoglobulin G2 (IgG) western immunoblot (WB) for Lyme disease, OR 3. A positive single-tier IgG2 WB test for Lyme disease.

Exposure to Lyme disease

-Exposure is defined as having been (less than or equal to 30 days before onset of EM) in wooded, brushy, or grassy areas (i.e., potential tick habitats) of Lyme disease vectors. Since infected ticks are not uniformly distributed, a detailed travel history to verify whether exposure occurred in a high or low incidence state is needed. -An exposure in a high-incidence state is defined as exposure in a state with an average Lyme disease incidence of at least 10 confirmed cases/ 100,000 for the previous three reporting years. -A low-incidence state is defined as a state with a disease incidence of <10 confirmed cases/100,000. -A history of tick bite is not required.

Life cycle of Lyme Disease vector

-Immature ticks (larvae & nymphs) acquire infection-causing Borrelia burgdorferi bacteria by feeding on rodents, small mammals, & birds during spring & summer months -Bacteria are maintained through tick life cycle from larva to nymph and from nymph to adult -Bacteria are primarily passed to humans from nymphs and less frequently by adults

The Future of Lyme Disease

West Nile Virus (WNV)

-Leading cause of mosquito-borne disease in US -Transmitted to humans through bite of infected mosquito • 70-80% of people infected with WNV do not feel sick • 20-30% of people who are infected develop acute systemic febrile illness (headache, fever, muscle pains, rash, intestinal problems) • About 1 out of 150 infected people develop a serious and sometimes fatal neuroinvasive illness (meningitis, encephalitis, or myelitis)

West Nile virus transmission cycle

Incidence of West Nile neuroinvasive disease

Climate impacts on West Nile virus transmission

Climate change will significantly affect vector-borne disease incidence, but predicting the specific future trends is difficult because of the complexity involved

-Vectors may be affected in terms of: • Population size & density • Growth and survival rates • Seasonality • Geographic distribution • Ability to carry or transfer pathogen -Hosts may be affected in terms of: • Population size & density • Geographic distribution • Availability in environment • Activity patterns • Landscape features and land use • Public health changes • Mass migration

First genetically modified mosquitos released in the United States

-Aedes aegypti makes up about 4% of mosquito population in the Keys, but it is responsible for practically all mosquito- borne disease (dengue, Zika) transmission -Phase 1: 12,000 males released over 12 weeks -Phase 2: 20 million males released over 16 weeks

What is microcephaly?

Microcephaly is a condition where babies are born with abnormally small heads that is caused by the zika virus.

What does congenital transmission mean?

Congenital transmission is when an infection is transmitted from a mother to a baby during pregnancy or delivery.

Which mosquito species carry Zika virus?

The Aedes species carries Zika.

What other diseases are carried by this specific species of mosquitoes in the Western hemisphere?

Yellow fever, Dengue and Chikungunya.

Besides OXITEC’s approach, what are some of the other methods used to reduce the spread of mosquito-borne disease?

Many people have used insecticides and fumigation to kill off the mosquitos.

In general, how were these genetically modified (GM) mosquitoes produced?

The scientists synthesized some DNA that had a lethality gene and a fluorescent marker which they then inserted into the genomes of mosquito eggs.

What chemical is used as the antidote to the lethality gene?

Tetracycline.

Prior to release in the wild, GM male and females are separated, how can scientists tell them apart?

The male pupae are much smaller than the females, so they are separated in the pupae stage by size.

Why are only GM males released into the wild?

Only the males are released because they don’t bite people and spread disease, but they do live long enough to breed with the wild females.

Why should people not be worried about being bitten by the GM male mosquitoes?

Male mosquitos do not bite people they just live to breed with the females and pass on their genes to their offspring.

What happens to the offspring produced from GM males mating with females in the wild?

All the offspring will die before reaching maturity because they inherit the lethality gene but are not fed tetracycline which they are genetically dependent on.

What is the evidence that releasing GM mosquitoes in the wild is effective at reducing mosquito populations?

Most of the offspring of the GM male and wild female inherit the male’s lethality gene and die. The video references the fact that studies have shown that repeated releases of the GM mosquitos into an area can reduce the mosquitos in a village by 95%.

What concerns might non-scientists or people living in the experimental area have about this strategy?

Some people may have environmental concerns, as a reduce in the mosquito population could affect the ecology of the area, there are plenty of animals in the area that may rely on the mosquitos as a food source so to reduce the mosquito populations by that much may hinder the ecology of the area.

Malaria Parasites in Human Body

•3 different stages of parasite during human life cycle 1. Sporozoites traveling from bite site to liver 2. Intracellular liver parasite 3. Erythrocyte (RBCs) stage parasite •Parasite “looks” different in each stage (has different forms & proteins on outside) •So immune system has to recognize & attack 3 unique versions of parasite

Malaria Parasites in Human Body

Parasite has to overcome many layers of immune defenses in order to move through body, survive, & replicate

Layers of defense

Skin Immunity

-Physical: skin cells in epidermis form strong, water-proof barrier -Chemical: skin cells produce anti- microbial proteins to kill parasites. Low pH also kills parasites. -Cellular: skin contains both innate and adaptive immune cells ready to respond to parasites

Skin Immunity

Cellular: innate cells include... a. Dendritic cells (includes Langerhans cells and dermal dendritic cells) b. Macrophage cells c. Mast cells

Innate Immune Cell: Dendritic cells

-Functions: 1. Capture & destroy pathogens & parasites by phagocytosis (innate immunity) 2. Influences activity of other innate immune cells (innate immunity) 3. Process and present pathogen/parasite antigens to naïve T-cells in lymph nodes (adaptive immunity) •Long-lived cells •Located near barriers

Innate Immune Cell: Macrophage cells

Functions: 1. Kill microbes, infected cells, tumor cells by phagocytosis (innate immunity) 2. Secrete chemicals & cytokines to promote inflammation & fever (innate immunity) 3. Process and present pathogen/parasite antigens to help T-lymphocytes learn and do their job (adaptive immunity) •“Big eaters” •Large phagocytic cells •Found in most tissues •Essential for clean up of cellular debris and apoptotic cells

Phases of Phagocytosis

Phases of Phagocytosis

Bactericidal agents produced or released by phagocytes on the ingestion of microorganisms. Most of these agents are made by both macrophages and neutrophils.

Innate Immune Cell: Mast cells

Functions: -When activated will release contents of large granules to try to kill nearby pathogens and parasites & to attract other immune cells to area (innate immunity) -Also produce chemicals that promote inflammation (innate immunity) •Found near blood vessels in connective tissue, intestinal lining, & airway mucosa

Skin Innate Immunity

-Dendritic cells (Langerhans & dermal dendritic cells) and -Macrophage cells will try to use phagocytosis to engulf & destroy sporozoites *These cells are also important for training B and T cells to recognize sporozoites in future -Mast cells will release granules to try to kill sporozoites if properly stimulated

Malaria Parasites in Human Body

Defense #1: -Skin contains physical, chemical, and cellular barriers -These defenses are partially successful: about 50% of sporozoites injected into skin by mosquito are trapped or killed -But, other 50% of sporozoites move to other parts of body

Malaria Parasites in Human Body

-Sporozoites enter blood vessels and travel to liver -Defense #2: Innate immune cells in blood attempt to kill travelling sporozoites: Neutrophils Basophils Eosinophils Monocytes Natural killer cells

Blood Innate Immune Cell: Neutrophil

Key Features & Functions: 1. Most numerous & important innate immune cell 2. Lots of phagocytosis 3. Responds to and promotes inflammation

Blood Innate Immune Cell: Monocyte

Key Features & Functions: 1. Important function = phagocytosis 2. Enter tissue and become macrophages 3. Produce cytokines that function in defense

Blood Innate Immune Cell: Eosinophils

Key Features & Functions: 1. When activated, granules release enzymes to kill large extracellular parasites 2. Release chemicals that promote inflammation 3. Capable of phagocytosis (but not major function)

Blood Innate Immune Cell: Basophils

Key Features & Functions: 1. When activated, granules release cytokines and enzymes to kill large extracellular parasites 2. Release chemicals (histamine, leukotrienes, and prostaglandins) that promote inflammation

Blood Innate Immune Cell: Natural Killer Cell

•Use chemicals to do their job •Contribute to inflammation •Function: − Kill virus-infected cells − Kill tumor cells − Kill abnormal cells − Regulate other immune cells Blood natural killer cells don’t play much of a role in fighting malaria parasites

Malaria Parasites in Human Body

Defense #2: Immune cells in the blood attempt to kill the travelling sporozoites Neutrophils, Basophils, Eosinophils, & Monocytes may respond to presence of sporozoites in blood and try to kill or neutralize them (i.e. stop them from infecting a cell)

Malaria Parasites in Human Body

-Sporozoites enter liver Defense #3: a. Innate immune cells attempt to kill sporozoites -Macrophage b. Infected liver cells produce interferons (IFNs) that alerts immune system that they are infected by parasite -Natural killer cells in liver will respond and kill infected cells

Malaria Parasites in Human Body

-Merozoites leave liver and begin infecting and replicating in Red Blood Cells -Defense #4: Innate immune cells in the blood attempt to kill merozoites: Neutrophils Basophils Eosinophils Monocytes Natural killer cells

Malaria Parasites in Human Body

-What about adaptive immune responses involving T and B cells? -Defense #5: T lymphocytes and B lymphocytes target and attack malaria parasites

Malaria Parasites in Human Body

-How do T lymphocytes and B lymphocytes help to fight malaria infection? -First, they need to learn there’s an infection. Dendritic cells & macrophages tell them. -Second, they need to fully mature & replicate to create an army of identical cells ready to attack their specific target -Third, they need to find the target in the body

Adaptive Immune Cell: T lymphocytes (T cells)

1. Cytotoxic T-lymphocytes (Killer T cells): Kill cells infected by pathogen & cancer cells 2. Helper T cells: activate other immune cells to do work i. Type 1 Helper T cells (TH1) activate macrophages and natural killer cells to destroy intracellular pathogens ii. Type 2 Helper T cells (TH2) activate eosinophils and stimulate B cells; enhance responses to worms & allergens iii. Type 17 Helper T cells (TH17) stimulate inflammatory response; respond to fungi & bacteria 3. T regulatory cells: inhibit functions of other T cells, dendritic cells, & B cells

Plasma cells

Mature B cells that produce huge amounts of many different types of antibodies

Antibody

Y-shaped proteins that specifically target & stick to foreign cells causing immune responses

Memory cells

Retain copy of B cell receptor for future use

B cells effect on parasites

B cells can make antibodies that target the proteins on the outside of all the different malaria life stages

Antibodies can have several different functions:

1. Neutralization: can make malaria parasites toxins less harmful 2. Opsonization: can make innate cells more likely to phagocytize malaria parasites 3. Complement activation: can “turn on” other innate immune systems to attack malaria parasite

Antibody Levels after 1st and 2nd Exposures

-After 1st exposure, it takes time for new plasma & memory cells to develop -After 2nd exposure, memory cells are already there & can become plasma cells quickly This results in: 1. Stronger response 2. Quicker response

Vaccine

A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease

Vaccination

administration of a vaccine in order to generate a protective immune response in an individual

Immunization

Act of inducing a protective immune response against a specific pathogen/disease through deliberate (i.e. vaccination) or unintended (i.e. natural infection) means

Steps for a successful immunization

Vaccine introduces a small component (i.e. foreign antigen) or a non-harmful form of the pathogen into body 2. Body’s immune system produces an immune response, involving antibodies & killer and helper T cells, against the antigen or weakened pathogen 3. After immune response is over, a small group of memory B cells & T cells remain in body for a long time, ready to respond quickly and intensely if they “see” their target again 4. When real pathogen is encountered in future, immune memory cells “remember it” & mount much larger and quicker response than it would have if body had never received the vaccine 5. This larger, quicker immune response can act in several ways to fight infection and/or prevent associated disease

Specific features of effective vaccines

Induces protective T cells: -Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses Induces neutralizing antibody: -Some pathogens (e.g. poliovirus) infect cells that can’t be replaced (i.e. neurons). Neutralizing antibody prevents infection of such cells.

Adjuvants

-Substance give with antigen that enhances immune response to the antigen (enhances immunogenicity) -Adjuvants may enhance immunogenicity in two ways: 1. Adjuvants convert soluble protein antigens in particulate matter which makes it easier for them to be engulfed by antigen-presenting cells (such as macrophages) •Include aluminum (hydroxide or phosphate), oil-in-water emulsions, CpG motifs 2. Adjuvants stimulate immune response, e.g. inflammation •Adding dead bacteria or bacterial parts, viral proteins

Evidence of Vaccine Effectiveness

-Among 78.6 million children born in U.S. between 1994 and 2013, vaccination was estimated to prevent: •322 million illnesses •21 million hospitalizations •732,000 premature deaths -In economic terms, vaccination provided net cost savings of: •$295 billion in direct costs •$1.38 trillion in societal costs

Types of Vaccines

Vaccine Hazards

•Most common = local, injection site reactions (swelling, redness, and/or soreness) due to immediate non-allergic immune responses •Allergic reaction to vaccine component 1. Immediate reactions occur minutes to 1 hour after. Symptoms range from mild and localized (1 in 50,000 doses) to severe anaphylaxis (1 in 1,000,000 doses) 2. Delayed reactions occur 3 to 6 hours after exposure

Allergic reaction to vaccine

•Residual media used to grow organisms (yeast, milk proteins) •Adjuvants (aluminum salts) •Stabilizers (gelatin) •Antibiotics •Preservatives •Trace amounts of latex from vial stoppers or syringe plungers

Non-Allergy Vaccine Hazards

1. Vaccines from attenuated organisms can cause progressive disease in very rare cases •Vaccine form multiplies too fast or mutates to be more pathogenic •E.g. measles, mumps, rubella, oral polio, BCG •Highest risk in immunocompromised individuals •Risk to fetus if given to pregnant women 2. Contamination with live or other pathogen during manufacturing or delivery (e.g. multi-use vials) - Cutter incident: In 1955, two batches of Salk polio vaccine produced by Cutter Labs contaminated with live virus leading to abortive polio in 40,000 people, 51 cases paralysis, 5 deaths 3. In rare cases, may act as trigger for underlying disease/disorder - Weakened, replicating vaccines have triggered seizure disorders 4. By chance, people who receive vaccines will get sick and/or have adverse events - Correlation is not causation

Vaccine Safety Evaluation

Vaccine Safety Monitored Post-Approval

Billions of doses of vaccines given to Americans in the 30 years of injury program’s existence. During that time, about 21,000 people filed claims.

Vaccine Risks

•Serious side effects from vaccination are rare •Vaccine side effects are generally less severe than infection •Vaccine side effects generally similar to placebo

Rotavirus

Viral infection of young children causing diarrhea, vomiting, dehydration, fever, & abdominal pain In 2008, killed ~450,000 children <5 yrs (WHO)

Variolation

intentional infection of people with the smallpox virus, ideally a milder form of the virus. The goal was to transmit a mild form of the disease so that infected could recover and have immunity against more deadly forms. Disadvantages (compared to vaccination): 1. Resulted in ~2% death rate in those intentionally infected 2. People were immediately infectious after variolation

Inventor of Vaccination

Edward Jenner

Febrile Seizures

-Febrile seizures are seizures or convulsions that occur in young children and are triggered by fever -Fevers can be caused by common childhood illnesses like colds, the flu, an ear infection, or roseola. Rarely, vaccines can trigger seizures Most febrile seizures last only a few minutes and are accompanied by a fever above 101°F ~2-5% of young children between the ages of 6 months and 5 years old experience febrile seizures -Brief febrile seizures (<15 minutes) do not cause any long-term health problems. Seizures >15 minutes are generally harmless but do carry an increased risk of developing epilepsy

Vaccine Hesitancy

-Problem: Vaccine-preventable disease (VDP) may increase in frequency when people are under-vaccinated or non- vaccinated -Even vaccinated individuals can have important doubts and concerns regarding vaccination

Attitudes toward vaccines

-Accepters: agreed with or did not question vaccination -Vaccine-hesitant: accepted vaccination but had significant concerns about vaccinating their infants -Late vaccinators: purposely delayed vaccinating or chose only some vaccines -Rejecters: completely reject vaccination

Vaccine-hesitancy

is an individual behavior influenced by a range of factors