Controlling Disease

To control infectious disease we must consider such aspects as:

The origin of the outbreak (especially the natural reservoir)

Its mode of transmission within the population

The possible methods that can be employed to contain it

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Preventing theSpread of Disease

The best method of disease control is to prevent the disease spreading in the first place.

The four main methods by which the spread ofinfectious disease is controlled are through:

Behavioral controlModifying the environment Treatment Immunization

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Modifying the EnvironmentAll pathogens require certain conditions for growth, reproduction, and transmission.

By modifying the environment to make it less suitable for pathogens, most infectious diseases can be controlled.

Examples includeDraining swampy ground to eliminate breeding sites for mosquitoes carrying malaria and dengue fever.

Spraying disinfectantsto sterilize potentially contaminated surfaces.

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Workers spray drainage ditches

with insecticide to kill mosquitoes

Effective SanitationThe development of effective sanitation, sewage treatment, and the treatment of drinking water has virtually eliminated dangerous waterborne diseases from developed countries.

These practices disrupt the normal infection cycle of pathogens transmitted through the fecal-oral route, such as those causing typhoid fever and cholera.

Behavioral ControlTransmission of disease can be prevented or significantly reduced by adopting ‘safe’ behaviors.

Examples include:Using condoms to reduce the spread of sexually transmitted diseases.

Establishing quarantine and isolation procedures to prevent the spread of disease from other countries.

Adopting appropriate personal hygiene practices, such as washing your hands after going to the toilet and before handling food.

Immunization

Vaccination or immunization is a procedure that provides artificially acquired active immunity for the person receiving it.

A vaccine is a suspension of microorganisms (or portions of them) which protects people from disease by inducing immunity.

Vaccines that are effective against bacteria and viruses have been produced, but to date there are no useful vaccines for humans against protozoa, roundworms, flatworms, or fungi.

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The last known person in the world to have smallpox, 23 year old Ali Maow Maalin (photo), from Merka, Somalia. Smallpox was eradicated due to a vigorous vaccination program.

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Types of VaccineThere are two basic types of vaccine:subunit vaccines and whole-agent vaccines.

Recombinant vaccines

Toxoids

Conjugated vaccines

Acellular vaccines

Attenuated(weakened)

Inactivated(killed)

Subunit VaccineContains some part or product of micro-organisms that can produce an immune

response

Whole-Agent Vaccine

Contains whole, nonvirulent

microorganisms

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Subunit Vaccines 1Subunit vaccines contain some product of, or fragments of, microorganisms. These are capable of providing an immune response in the person receiving the vaccine.

Conjugated VaccinesSome pathogens produce polysaccharide capsules that are poorly antigenic, especially in young children.To enhance their effectiveness, they are combined with proteins such as toxoids from other pathogens.

Toxoid

attached

Polysaccharide

from pathogen

Recombinant VaccinesProduced using genetic engineering techniques when other microbes (bacteria and yeast) are genetically altered to make the desired antigenic fraction.

Yeast makes

viral proteins

Inactivated

toxins

Subunit Vaccines 2

ToxoidsToxoids are bacterial toxins that have been inactivated by heat or chemicals. When injected, the toxoid stimulates the production of antitoxins.

Heat, iodine or

formaldehyde

Acellular VaccinesThese are produced by fragmentation of a conventional whole-agent vaccine and collecting only those portions containing the desired antigens.

Antigenic

fragments of

bacterial cells

Whole Agent Vaccines

Whole agent vaccines contain complete microorganisms that are nonvirulent (not capable of causing disease).

They may be either inactivated whole or attenuated.

Many attenuated viruses provide recipients with life-long immunity (without the need for booster shots).An effectiveness of 95% is not unusual.

One danger of such vaccines is that these live viruses can back-mutate to a virulent form.

Inactivated: whole agent is

inactivated by treatment with

formalin or other chemicals

Attenuated: The agent is alive, but has been

significantly weakened. They are usually

derived from strains where mutations have

accumulated during long-term cell culture.

Mutated DNA

DNA VaccinesUsing genetic material to produce vaccines is one of the promising new fields of vaccine research.

Unlike traditional vaccines (which contain either whole or parts of a pathogen), genetic vaccines contain only the gene for producing an antigen from the pathogen.

When this gene is expressed in a patient the protein produced elicits an immune response.

Genetic vaccines are currently being developed and trialed to immunize people against:

Malaria

HIV

Herpes simplex

Hepatitis B

Rabies

Cancer HIVCancer

Hepatitis BHerpes simplex

Malaria

Rabies

Producing a DNA Vaccine 1

The recombinant bacteria are allowed to grow and reproduce on an agar plate.

Antigen gene is spliced into the plasmid and the plasmid is inserted back into the bacterium.

Gene for the antigen is removed from the pathogenic or cancerous cell

Plasmid is isolated from a harmless bacterium.

Producing a DNA Vaccine 2

Expression of the gene in the patient produces a protein that elicits an immune response.

The isolated antigen gene is delivered to the patient using direct injection or via a gene gun.

Antimicrobial DrugsAntimicrobial drugs include synthetic (manufactured) drugs as well as drugs produced by bacteria and fungi, called antibiotics.

Antibiotics are produced naturallyby microorganisms as a means ofinhibiting competitor microbesaround them (a form of antibiosis,hence the name applied to the drugs).

The first antibiotic, called penicillin, was discovered in 1928 by Alexander Fleming.

Since then, similar inhibitory reactions between colonies growing on solid media have been commonly observed.

Antibiotics are actually rather easy to discover, but few of them are of any medical or commercial value.

Agar plate with bacterial colonies and antibiotic discs

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Antimicrobial Effectiveness 1

To be effective, antimicrobial drugs must often act inside the host so their effect on the host’s cells and tissues is important.

The ideal antimicrobial drug has selective toxicity, killing the harmful organism without damaging the host.

Some antimicrobial drugs have a narrow spectrum of activity and affect only a limited number of microbial types.

The wrong antibiotic can allow infections such as this ulcer to get out of control

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Antimicrobial Effectiveness 2

Other drugs affect a large variety of microbes and are therefore called broad-spectrum drugs.

The identity of a pathogen is not always known. Therefore a broad-spectrum drug may be prescribed in order to save valuable time.

However there is a disadvantage with this practice. Broad spectrum drugs not only target the pathogen, but also the host’s normal microbial community (flora).

Staphylcoccus aureus infectionThe sticky looking substance is a polysaccharide biofilm,

which protects the bacteria from antibiotics. Some strains of staph. have developed resistance to multiple antibiotics. The

wide use of broad-spectrum antibiotics has contributed to this.

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Antimicrobial Activity

Spectrum of antimicrobial activity of

a number of chemotherapeutic drugs

Prokaryotes

MycobacteriaGram-Negative

BacteriaGram-Positive

BacteriaRickettsias/Chlamydias

Penicillin

Tetracycline

Isoniazid

Streptomycin

Viruses

Acyclovir

Antimicrobial ActivitySpectrum of antimicrobial activity of a number of chemotherapeutic drugs

Eukaryotes

Fungi ProtozoaTapeworms/

Flukes

KetoconazoleNicosamide(tapeworms)

Mefloquine(malaria)

Praziquantel(flukes)

How Antimicrobial Drugs Work

Antimicrobial drugs disrupt the functioning of a bacterial cell in the following ways:

Inhibited Protein SynthesisTranslation is disrupted. Examples: erythromycin, tetracyclines, chloramphenicol, streptomycin

Damaged Cell WallsThe synthesis of new cell walls during cell division is inhibited.Examples: penicillin, vancomycin, cephalosporins, bacitracin

Damaged Plasma MembraneThe plasma membrane may be ruptured. Examples: nystatin, miconazole, polymyxin B, amphotericin B

Inhibition of Enzyme ActivityThe synthesis of essential metabolites is inhibited. Examples: sulfanilamide, trimethoprim

Inhibit Gene CopyingDNA replication and transcription are interfered with. Examples: Rifampin, Quinolones

Monoclonal AntibodiesA monoclonal antibody is an artificially produced antibody that neutralizes only one specific protein (antigen).

Monoclonal antibodies are produced by stimulating the production of B-cells in mice injected with the antigen.

These B-cells produce an antibody against the antigen.

B-cells can be isolated and made to fuse with immortal tumor cells.They can then be cultured indefinitely in a suitable growing medium.

Monoclonal antibodies are useful for 3 reasons:

They are totally uniform (i.e. clones).

They can be produced in large quantities.

They are highly specific.Monoclonal antibodies chemically

linked to a fluorescent dye to

detect the presence of gonorrhea

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Making Monoclonal Antibodies

Hybridoma cells

Mouse cell and tumor cell fusing

Unfused cell

Pure tumor cells are

harvested from culture

A mouse is injected with a

foreign protein (antigen).

The mouse’s B-cells produce an

antibody to recognize the antigen.

A few days later, antibody-

producing B-cells are taken

from the mouse’s spleen.

The mouse cells and

tumor cells are mixed

together in suspension.

Some of the mouse cells fuse

with tumor cells to make hybrid

cells called hybridomas.

Hybridomas are screened for

antibody production. They are then

cultured to produce large numbers

of monoclonal antibodies.

The mixture of cells is placed in

a selective medium that allows

only hybrid cells to grow.

The World Health Organization

Founded in 1948, the World Health Organization (WHO) is a specialized agency of the United Nations

WHO promotes technical cooperation for health among nations, carries out programs to control and eradicate disease, and strives to improve the quality of human life.

WHO has four main functions: To give worldwide guidance in the field of health

To set global standards for health

To cooperate with governments in strengthening national health programs

To develop and transfer appropriate health technology, information and standards

A major event in WHO's first 50 years was the global eradication of smallpox.

The Role of the CDCThe Center for Disease Control and Prevention (CDC) is an agency of the US Department of Health and Human Services.

In today's global environment, new diseases have the potential to spread across the world in a matter of days, or even hours, making early detection and action more important than ever.

The CDC plays a critical role in investigating, monitoring and controlling these diseases, traveling at a moment's notice to investigate outbreaks worldwide.

CDC and Zairian scientists

take samples from

animals collected near

Kikwit, Zaire, 1995. These

samples were sent back to

CDC in Atlanta for testing

to search for the animal

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