SUMMARY-Nobody Is Immune

Summary-Nobody Is Immune(PCL WEEK 8)

1) Immune system

(A network of cells, tissues, and organs that work together to defend the body against attacks by pathogens)

First line of defence (Skin, Lysozyme, Clotting of blood, Mucus and cilia)

Second line of defence (innate immune system (non-specific) and adaptive immune system (specific); Involves leukocytes)

Immunity (Active and passive; Natural and Artificial)

Herd Immunity

If immunity rates in a society is high, then protection will aslo be conferred to those who are unvaccinated.

2) Pertussis

i) Incidence & Prevalence

According to age (US):

2001-2003

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1-4 years – 12 %

5-9 years - 9%

10-19 years – 33%

20 years - 23%

In Malaysia

Decrease after introduction of vaccine

0.02 per 100 000 population. (2006)

ii) Causes & Predisposing factors

Caused by a bacteria called Bordatella pertussis

Predisposing factors: Direct/Indirect Contact, Airbone droplets, Not being immunized.

iii) Pathophysiology
-Typically attacks children
-3 stages : Catarrhal àParoxysmalàConvalescent
Pathophysiology :
-Bordetella pertussis attaches to and multiplies on the respiratory epithelium. This damages ciliated respiratory epithelium.
-The damage starts in the nasopharynx and ends primarily in the bronchi and bronchioles
-Cilia is attacked by bacteria and with the accumulation of debris in the respiratory tract, mucus is produced
-As the body can’t get rid of the mucus in the airways, coughing and inhalation with a whistling or whooping sound entails.
-This causes difficulty in breathing
Whistling/whooping sound :
-Narrowing of the lower respiratory tract and is caused by mucus
-Air moves through the narrowed space, it sounds like whistling or whoosing.
-Often comes from the small breathing tubes (bronchial tubes) deep in the chest

iv) Complications & Symptoms

The first stage- runny nose, sneezing, low-grade fever, mild, occasional cough, similar to the common cold.

The second stage-Bursts (paroxysms) , breathing in accompanied by a characteristic high-pitched "whoop" sound, individual may become cyanotic (turn blue) from lack of oxygen, Children and young infants appear especially ill and distressed, Vomiting and exhaustion

The third stage -The cough becomes less paroxysmal and usually disappears

Complications -secondary bacterial pneumonia,seizures,encephalopathy,reactive airway disease,dehydration,malnutrition.

v) Differential Diagnosis

1. Asthma

Pertussis is also associated with vomiting and sputum. To confirm whether it is asthma or pertussis a definitive culture diagnosis or blood-work is done.

2. Pneumonia

Pertussis is not asscociated with joint pains and shaking chills. Hence, pneumonia is ruled out.

3. Tuberculosis

Lupus vulgaris and chroiditis is not associated with the symptoms of Pertussis. Hence Tuberculosis is ruled out.

4. Febrile Seizures

Pertussis is not associated with otitis media. Hence, Febrile seizure is ruled out.

Diagnosis:

Suggested clinically by the the characteristics of the whooping cough and a history of contact with an infected individual. It is confirmed by the isolation of the organism. Cultures or swabs of nasopharyngeal secretions result in a higher positive yield than cultures of ‘cough plates’.

Workup

Laboratory Studies - Blood work, Cultures, Direct fluorescent antibody (DFA) studies, Enzyme-linked immunosorbent assay (ELISA), Imaging Studies.

vi) Management & Treatment

Medical Care

· The goals of therapy include limiting the number of paroxysms, observing the severity of cough, providing assistance when necessary, and maximizing nutrition, rest, and recovery.

· Hospitalization-Monitor heart rate, respiratory rate, and oxygen saturation of hospitalized patients continuously, especially in relation to coughing paroxysms. Coughing, feeding, vomiting, and weight changes should be recorded.

· Pay attention to the young infant's hydration and nutritional status.

· Patients who are severely ill may require treatment in an ICU.

Medication - Antimicrobial agents, Pertussis-specific immune globulin ,Antibiotics(oral (PO) erythromycin, macrolide antibiotics(erythromycin, clarithromycin, and azithromycin, trimethoprim-sulfamethoxazole).

vii) Prevention – Maintain hygiene, Avoid contact with infected people, Isolation, Vaccination and Booster vaccination, Education.

3)Safety of vaccination & Immunisation schedule

1) Greatest success story in public health: reduction of infectious diseases resulting from the use of vaccines.
eg. Reduced preventable infectious diseases (measles, pertussis, diphtheria)

2) Prior to approval by FDA, vaccines are tested extensively by scientists to ensure they are effective and safe. But no vaccine is 100% safe or effective. (depends on individual immune systems)
- Mice, guinea pigs, rabbits, monkeys
- FDA approves clinical studies
- Human subjects (voluntary), computers used to predict how the vaccine will interact with the immune system
- 3 phases: small (20-100 volunteers) a few months,
larger (several hundred volunteers) months to years,
larger still (several hundreds to thousands) several years.

3) Agencies involved in vaccine safety regulation:
a) National Vaccine Program Office (NVPO) under National Childhood Vaccine Injury Act (NCVIA)
- Vaccine Adverse Event Reporting System (VAERS) by CDC and FDA in 1990
- National Vaccine Injury Compensation Program (NVICP)
b) Department of Health and Human Services (DHHS)
- Centers for Disease Control and Prevention (CDC),
- Food and Drug Administration (FDA)
- National Institutes of Health (NIH)
- Health Resources and Services Administration (HRSA).

4) Six Common Misconceptions By CDC 29 May 2007

Immunization Schedule (2007)

BCG (birth), DtaPHibHep(2,3,5 months), DTwPHib(2,3,5,18 months), HepB(birth,2,3,5 months),IPV(2,3 months), JapEnc(9,10,18 months;5,8,11,14 years), Measles ( 6months), MenACWY (Hajj Pilgrims), MMR(12 months;7 years), OPV (2,3,5,18 months; 7 years), TT(15 years), Typhoid(food handlers), YF (visitors to Yellow fever endemic countries)

4)Role of parents and government on protecting infectious diseases(Covered in Mock-Trial)

Role of Government:

· monitoring, analysing and reporting on vaccine preventable diseases (VPDs) as well as bacterial, bloodborne and sexually transmitted diseases

· providing timely, accurate and relevant surveillance advice to inform policy and response activities relating to VPDs, including pandemic planning

· providing stakeholders with information on the impacts that VPDs and other communicable diseases could pose to Australia, including through cross-jurisdictional and international trend analysis

· managing and contributing to committees on VPD and other communicable disease issues

· engaging data providers and stakeholders to enhance collection and collation of VPD information.

Role of family:(maintain hygiene, immunization, nutrition, healthy lifestyle)

5)Legal & social implications on not getting child immunised(Covered in Mock-Trial)

· Patients autonomy, Children and Young Persons Act 1933, Assessment of vaccination, Herd Immunity

Safety of Vaccination

Vaccine Safety - Introduction

1) Greatest success story in public health: reduction of infectious diseases resulting from the use of vaccines.
a) Eradication of smallpox
b) Near elimination of wild polio virus
c) Reduced preventable infectious diseases (measles, pertussis, diphtheria)

2) During the last 10 years, the FDA has recalled only three vaccine lots: one was mislabeled, another was contaminated during production, and the third was recalled after the FDA discovered potential manufacturing problems at a production plant.

3) Prior to approval by FDA, vaccines are tested extensively by scientists to ensure they are effective and safe. But no vaccine is 100% safe or effective. (depends on individual immune systems)
- Mice, guinea pigs, rabbits, monkeys
- FDA approves clinical studies
- Human subjects (voluntary), computers used to predict how the vaccine will interact with the immune system
- 3 phases: small (20-100 volunteers) a few months,
larger (several hundred volunteers) months to years,
larger still (several hundreds to thousands) several years.

4) Agencies involved in vaccine safety regulation:
a) National Vaccine Program Office (NVPO) under National Childhood Vaccine Injury Act (NCVIA)
- Vaccine Adverse Event Reporting System (VAERS) by CDC and FDA in 1990
- National Vaccine Injury Compensation Program (NVICP)
b) Department of Health and Human Services (DHHS)
- Centers for Disease Control and Prevention (CDC),
- Food and Drug Administration (FDA)
- National Institutes of Health (NIH)
- Health Resources and Services Administration (HRSA).

5) In the last decade, numerous changes in vaccine production and administration have reduced the number of side effects and resulted in safer vaccines. (e.g A more purified acellular pertussis (aP) vaccine has been licensed for use and has replaced the whole cell pertussis vaccine used in DTP (diphtheria, tetanus, pertussis vaccine) – less mild and serious side effects.)


Six Common Misconceptions By CDC 29 May 2007 (will be explained)

1) Diseases had already begun to disappear before vaccines were introduced, because of better hygiene and sanitation.
2) The majority of people who get disease have been vaccinated.
3) There are "hot lots" of vaccine that have been associated with more adverse events and deaths than others. Parents should find the numbers of these lots and not allow their children to receive vaccines from them.
4) Vaccines cause many harmful side effects, illnesses, and even death - not to mention possible long-term effects we don't even know about.
5) Vaccine-preventable diseases have been virtually eliminated from the United States, so there is no need for my child to be vaccinated.
6) Giving a child multiple vaccinations for different diseases at the same time increases the risk of harmful side effects and can overload the immune system.

References:
http://www.who.int/immunization_safety/aefi/immunization_misconceptions/en/print.html
http://www.cdc.gov/vaccines/vac-gen/6mishome.htm
http://www.cdc.gov/vaccines/vac-gen/side-effects.htm#dtap

Immune system, Herd immunity - EDITED

Immune system

A network of cells, tissues, and organs that work together to defend the body against attacks by pathogens

Innate immune system (non-specific)

• Can respond to threats to the body in minutes
  
• has limited capacity for recognition of foreign material
  
• form body's first line of defense
  
• involves skin, lysozyme, clotting of blood, mucus, stomach acid, phagocytes
• examples of phagocytes:
  

Adaptive immune system (specific)

• can respond in an almost infinitely flexible manner
• depends on antigenic stimulation
  
• Has memory, i.e. capable of remembering an encounter with a microbe or other foreign substance, and can respond much more rapidly at the second encounter.
  
• Involves:
  
  • Production of antibodies
    
  • Killing of virally infected cells
    
• Involves lymphocytes

Immunity

• Active immunity (acquired immunity)
  
  • Natural
    
  • Artificial
    
    • vaccination
      
• Passive immunity
  
  • Natural
    
    • Antibodies obtained through breast feeding
      
  • Artificial
    
    • Antibodies injected into the body
      

Herd immunity

• If enough people in a community are immunised against certain diseases, then it is more difficult for that disease to get passed between those who aren't immunised.
  
• If most people around you are immune to an infection and can't get sick, then there is no one around to infect you, even if you aren't immune to the infection.
  
• Only apply to diseases that can be passed on from person to person
  
• only works if immunization rates in a community are high
  
• e.g. diphtheria, pertussis
  

There is an interesting animation about herd immunity. You guys may want to check it out.

http://www.immunisation.nhs.uk/About_Immunisation/Science/Herd_immunity_-_animation

PRedisposing factors

-direct contact with fluids from nose/mouth of infected people
-small bacteria-containing droplets in the air
-indirect contact such as towels
-not being immunized
-infected adults

Differential Diagnosis

1. Asthma
What is it: paroxysmal narrowing of the bronchial airways due to inflammation of the bronchi and contraction of the bronchial smooth muscle.

Symptoms: dyspnea (unpleasant or uncomfortable breathing), cough, and wheezing, chest tightness, shortness of breath

But: Pertussis is also associated with vomiting and sputum. To confirm whether it is asthma or pertussis a definitive culture diagnosis or blood-work is done.


2. Pneumonia
What is it: inflammation of the substance of the lungs/ Inflammatory illness in the lungs. It is usually caused by a bacteria

Symptoms: presence of cough, purulent sputum , fever ,nausea, vomiting, loss of appetite, joint pains, unusually rapid breathing, chest pains, muscle aches, high fever with shaking chills , cough producing yellow sputum.

But: Pertussis is not asscociated with joint pains and shaking chills. Hence, pneumonia is ruled out.


3. Tuberculosis
What is it: caused by Mycobacterium tuberculosis and occasionally M. bovis and M. africanum.

Symptoms: cough, wheezing, lupus vulgaris(presents on head or neck with red brown nodules), choroiditis(An inflammation of the layer of the eye behind the retina, either in its entirely (multifocal choroiditis) or in patches (focal choroiditis)).

But: Lupus vulgaris and chroiditis is not associated with the symptoms of Pertussis. Hence Tuberculosis is ruled out.


4. Febrile Seizures
What is it: convulsions brought on by a fever in infants or small children.

Symptoms: upper respiratory infection, otitis media(inflammation of the middle ear), viral syndrome, and they respond with comparably higher temperatures

But: Pertussis is not associated with otitis media. Hence, Febrile seizure is ruled out.

Diagnosis:
Suggested clinically by the the characteristics of the whooping cough and a history of contact with an infected individual. It is confirmed by the isolation of the organism. Cultures or swabs of nasopharyngeal secretions result in a higher positive yield than cultures of ‘cough plates’.

Workup

These tests can be conducted to confirm the diagnosis.
Laboratory Studies

1. Blood work
   Lymphocytosis is often profound (>70% of the total WBC count), especially in children.
   The WBC count often increases to 20-40,000 or even 100,000 cells/mm2.
   In adults, especially those that had been vaccinated, lymphocytosis is rare.
2. Cultures
   A definitive culture diagnosis is not always possible.
   Results of blood culture are uniformly negative because B pertussis grows solely in the respiratory epithelium.
   An immediately plated, deep, culture of a nasopharyngeal swab sample grown in Regan-Lowe charcoal agar or fresh Bordet-Gengou is considered the criterion standard for those who present within the first 3 weeks of their cough. The results are positive in <50% (perhaps 15-40%) of cases, and results become available too late (about 1 week) to be clinically useful. The CDC recommends this test to characterize the illness.
   Direct fluorescent antibody (DFA) studies
   DFA studies are performed by using a nasopharyngeal sample.
   Although the results can be available within minutes, its use is not recommended because of both low sensitivity and low specificity.
   Results are positive in 40-80% of patients and are now used to confirm most cases.
   Specimens should be obtained within the first 3 weeks of the disease (ie, in incubation, catarrhal, or early paroxysmal stages) or the sensitivity and specificity decrease.
3. Polymerase chain reaction (PCR) testing to detect DNA
   PCR testing may reveal <10 organisms per swab sample.
   Its sensitivity may be greater than that of culturing.
   False-positive results have been a problem, with some reports of more than 50%. Although this or a positive culture is the case definition for reporting pertussis to the CDC or WHO, some are now recommending ELISA confirmation before declaring an epidemic.
4. Enzyme-linked immunosorbent assay (ELISA) is also useful. Many now consider serologic testing with ELISA to be the criterion standard.
5. Imaging Studies
   Chest radiography may show focal atelectasis and/or peribronchial cuffing.
   The CDC recommends both culture and PCR tests if a patient has a cough lasting longer than 3 weeks.
   

Link:
http://emedicine.medscape.com/article/803186-diagnosis