Guys!

Can we compile this week's anatomy practical answers next week? Just bring your respective answers next Mon and we can compile them together! :)

Summary for Alan & Bill =)

AIDS VS HIV
AIDS
Official criteria- HIV-infected people who have fewer than 200 CD4 T cells.
HIV infection
Case definition- Adults, adolescents, or children aged ≥ 18 months, Children aged ≤ 18 months
Notifiable diseases
These are some of the notifiable diseases: AIDS, HIV infection, Cholera, Malaria, Measles, severe acute respiratory syndrome
Incidence and Prevalence
The number of cases reported in the world increases by year. In Malaysia, majority of the cases reported are male. (more will be shown during presentation)
Etiology
There are 3 major routes of transmission of the HIV(Sexual Transmission, Transmission via blood or blood products, Mother to Child Transmission)
The risk of transmission via tears, urine and saliva is considered to be negligible
Pathophysiology
• Entry to host cells (CD4+ lymphocytes, macrophages and monocytes) using gp120 with the help of chemokine co-receptors.
• Life cycle of HIV (8 stages):
1. Viral binding
2. Entry and Uncoating
3. Reverse transcription
4. Integration into host chromosomal DNA
5. Synthesis of viral DNA
6. Translation and production of Viral proteins
7. Assembly of virus and budding from the host cell
8. Maturation
• Then the virus is ready for infection
Investigation and Diagnosis
• HIV Antibody Testing :
-Detects HIV antibodies in blood or other body fluids
weeks after exposure or an HIV RNA test (viral load)
>detects the presence of the virus
• ELISA - (Enzyme-linked Immunosorbent Assay Test)
-A common serological test for the presence of particular antigens or antibodies (Serum)
-Direct and indirect
• Western Blot Test
• Home Collection Kit
• HIV Viral Load
• p24 Antigen Count Test
• CD4 Count
-measurement of how many functional CD4 T-cells are circulating in the blood.
Modes of transmission
• Having vaginal or anal sex without a condom with someone who is infected.
• Having contact with the blood of someone who has HIV. This could be having a blood transfusion from someone who is infected with HIV
• From a mother who has HIV to her baby: HIV can pass to the baby during pregnancy, during the birth of the baby, or through breast-feeding. Only about one in three babies born to HIV-positive mothers get HIV.
• Receiving an injection from an unsterilized needle that was previously used by someone with HIV.
• Heterosexual transmission is the route by which most people with AIDS have become infected with HIV worldwide
This category of AIDS cases is also among the most rapidly increasing.
Signs and Symptoms of HIV infection
Symptoms Early After Infection - Acute HIV : fever, headache, muscle and joint pain, sore throat, rash, diarrhea.
Later Symptoms Of HIV Infection
it takes about eight to nine years between the time of infection and the appearance of later symptoms, although this varies from person to person.
These symptoms signal that immune system function is deteriorating, due to declining numbers of CD4+ T cells
Symptoms of the Immune System: Swollen lymph nodes in the neck, axilla, or groin (lymphadenopathy), fever / night sweats
Symptoms of the GI Tract : Rapid weight loss, Diarrhea, Poor appetite, Profound fatigue
Respiratory Symptoms
usually occur later in course of the disease
Any cough or shortness of breath could be a sign of bacterial pneumonia or pneumocystis (carinii) jiroveci pneumonia (PCP).
Shortness of breath
Dry cough / productive cough
Symptoms of the Skin and Mucous Membranes
result of infection by other viruses, fungi or bacteria. Often, these infections involve the skin or mucous membranes (for example, inside the mouth).
HIV Effects on Dental Health
Skin rash
Genital sores (sores around the penis or vagina)
Red, brown, pink or purple lesion on the skin - suggestive of Kaposi's sarcoma
White patches on the tongue, inside of the mouth, or gums - could be signs of thrush, candida, or hairy oral leukoplakia
Canker sores / apthous ulcers
Neurological / Emotional Symptoms
Depression
Numbness, tingling, or burning in the feet, hands, or face. (peripheral neuropathy)
Confusion, weakness, or changes in level of consciousness
memory loss
Blurred vision
Complications
Bacterial
- Pneumonia
- Mycobacterium avium complex
- Tuberculosis
- Salmonellosis
Viral
- Cytomegalovirus
- Viral hepatitis
- Herpes simplex virus
- Human papillomavirus
Fungal infections
- Candidiasis
- Cryptococcal meningitis
Parasitic
- Pneumocystis carinii pneumonia
- Toxoplasmosis
- Cryptosporidiosis
Cancers
- Kaposi’s sarcoma
- Non-Hodgkin’s lymphoma
Neurological complications
Management and Treatment
Counsellingproper counselling before and after testing with informed consent especially patients tested positive to address issues such as stigma and the fear of disclosure of one's HIV status
Support Groups
Initiation of Antiretroviral Therapy (Antiretroviral drug treatment)
Combination Therapy (combination of 2 or more drugs)
Home based care (patient staying at homeable to work and do daily chores)
Traditional/Alternative Medicine
Prevention
Effective HIV prevention interventions include
• Condom use, Male circumcision, Provision of clean injecting equipment, Opioid substitution therapy, treatment of sexually transmitted infections, HIV testing and counselling, A set of interventions to prevent mother-to-child transmission of HIV, Sex education
In health care settings, transmission of HIV can be prevented through
• primary prevention measures
• secondary prevention measures
In addition, there is increasing evidence indicating that
• antiretroviral therapy programmes
• Current research on new prevention technologies such as microbicides, topical and oral antiretroviral pre-exposure prophylaxis
HIV prevention - combination behavioural change approach has been
• Abstinence, including delay of sexual initiation or debut
• Being safer by being faithful to one’s partner or reducing the number of sexual partners, and
• correct and consistent Condom use.
Legal and Ethical Issues
o Consent for medical examination and treatment
o Prenatal HIV Testing
 Recommended by Institute of Medicine Panel:
o Confidentiality
 Exception
o The Doctor & The Law Courts
o Release of Information to a third party

Signs and Symptoms of HIV infection

Symptoms Early After Infection - Acute HIV

fever, 

headache, 

muscle and joint pain, 

sore throat, 

Rash,

Diarrhea.

Later Symptoms Of HIV Infection

it takes about eight to nine years between the time of infection and the appearance of later symptoms, although this varies from person to person.

These symptoms signal that immune system function is deteriorating, due to declining numbers of CD4+ T cells

Symptoms of the Immune System 

Swollen lymph nodes in the neck, axilla, or groin (lymphadenopathy)

Fever / night sweats 

Symptoms of the GI Tract 

Rapid weight loss

Diarrhea

Poor appetite

Profound fatigue

Respiratory Symptoms

usually occur later in course of the disease

Any cough or shortness of breath could be a sign of bacterial pneumonia or pneumocystis (carinii) jiroveci pneumonia (PCP).

Shortness of breath

Dry cough / productive cough

Symptoms of the Skin and Mucous Membranes 

result of infection by other viruses, fungi or bacteria. Often, these infections involve the skin or mucous membranes (for example, inside the mouth).

HIV Effects on Dental Health

Skin rash

Genital sores (sores around the penis or vagina)

Red, brown, pink or purple lesion on the skin - suggestive of Kaposi's sarcoma

White patches on the tongue, inside of the mouth, or gums - could be signs of thrush, candida, or hairy oral leukoplakia

Canker sores / apthous ulcers

Neurological / Emotional Symptoms

Depression

Numbness, tingling, or burning in the feet, hands, or face. (peripheral neuropathy)

Confusion, weakness, or changes in level of consciousness

memory loss

Blurred vision

What Symptoms Signal The Onset Of AIDS?

A CD4+ T cell count of less than 200, and/or

At least one of more than two dozen opportunistic infections and conditionsIn the United States, the most common AIDS-defining condition in both women and men is a lung infection called Pneumocystis carinii pneumonia, abbreviated PCP.

Other AIDS-defining conditions include severe body wasting and Candida infection of the esophagus, windpipe, or lungs.

Reference:

CDC

http://www.cdc.gov/hiv/resources/qa/qa5.htm

About.com

http://aids.about.com/od/newlydiagnosed/a/hivsymptom.htm

ehealthMD

http://www.ehealthmd.com/library/aids/ads_symptoms.html 

AIDS Etiology and Pathophysiology Summary

Summary

Etiology

There are 3 major routes of transmission of the HIV:

• Sexual Transmission
• Transmission via blood or blood products
• Mother to Child Transmission

The risk of transmission via tears, urine and saliva is considered to be negligible

Pathophysiology

• Entry to host cells (CD4+ lymphocytes, macrophages and monocytes) using gp120 with the help of chemokine co-receptors.
• Life cycle of HIV (8 stages):

1. Viral binding
2. Entry and Uncoating
3. Reverse transcription
4. Integration into host chromosomal DNA
5. Synthesis of viral DNA
6. Translation and production of Viral proteins
7. Assembly of virus and budding from the host cell
8. Maturation

• Then the virus is ready for infection

HIV vs AIDS, NOTIFIABLE DISEASES

AIDS

Official criteria

• HIV-infected people who have fewer than 200 CD4 T cells.
  

Case definition

• Tested positive for HIV antibody
  
• And have one or more of the following:
  • 10%body weight loss or cachexia, with diarrhea or fever, or both, intermittent or constant, for at least 1 month, not known to be due to a condition unrelated to HIV infection
  • Cryptococcal meningitis
    
  • Pulmonary or extra-pulmonary tuberculosis
    
  • Kaposi sarcoma
    
  • Neurological impairment that is sufficient to prevent independent daily activities not known to be due to a condition unrelated to HIV infection
    
  • Candidiasis of the eosophagus
    
  • Clinically diagnosed life-threatening or recurrent episodes of pneumonia, with or without etiological confirmation
    
  • Invasive cervical cancer
    

HIV infection

Case definition

• Adults, adolescents, or children aged ≥ 18 months
  
  • Must meet at least one the following criteria:
    
    • Laboratory criteria
      
      • Detection of antibody to HIV virus
        
      • Detection of HIV virus (viral antigen)
        
  • Clinical or other criteria
    
    • Condition that meet criteria included in the case definitions of AIDS
      
• Children aged ≤ 18 months
  
  • Must meet at least one of the following criteria
    
    • Laboratory criteria
      
      • Definitive
        
        • Positive result or report of detectable quantity on any of the following HIV virology (non-antibody) test
          
          • HIV nucleic acid detection
            
          • HIV p24 antigen test including neutralization assay
            
          • HIV isolation (viral culture)
            
      • OR
      • Presumptive
        
        • Does not meet criteria for definitive HIV infection
          
        • Has a positive result on only one specimen (excluding cord blood) using the above HIV virology tests
          
    • OR
      
    • Clinical or other criteria
      
      • If the laboratory criteria are not met and no other causes of immune suppression
        
      • Condition that meet the criteria included in 1987 pediatric surveillance case definition for AIDS which are
        
      • Candidiasis of the oesophagus, trachea, bronchi, or lungs
        
      • Cryptococcosis, extrapulmonary
        
      • Cryptosporidiosis with diarrhea persisting > 1 month
        
      • Cytomegalovirus diseases of an organ other than liver, spleen, or lymph nodes in patients > 1 month of age
        
      • Herpes simplex virus infection causing a mucotaneous ulcer persisting > 1 month; or bronchitis, pneumonitis, or oesophagitis for any duration in a patient >1 month of age
        
      • Kaposi sarcoma
        
      • Lymphoma of the brain ( primary)
        
      • Mycobacterium avium complex of M. kansasii disease, disseminated (site other than/in addition to lungs, skin, cervical, or hilar lymph nodes)
        
      • Pneumocystis carinii pneumonia
        
      • Progressive multifocal leukoencephalopathy
        
      • Toxoplasmosis of the brain in a patient >1 month of age
        
      • ≥2 bacterial infections within a 2-year period (septicaemia, pneumonia, meningitis, bone or joint infections) or abscess of an internal organ orr body cavity – excluding otitis media or superficial abscesses
        

Notifiable diseases

Other diseases:

• Acute flaccid paralysis (AFP)
  
• Rubella (adult type)
  
• Rubella (congenital syndrome)
  
• Haemophilus influenza disease
  
• Mumps
  
• Influenza-like illness
  
• Avian influenza
  
• Severe acute respiratory syndrome (SARS)
  

References:

http://www.dph.gov.my/survelans/Guidelines%202008/Case%20definition%20update.pdf

http://www.pharmacy.gov.my/self_care_guide/miscellaneous/Hiv%20infection%20And%20Aids.pdf

Modes of Trasmission

Having vaginal or anal sex without a condom with someone who is infected.

Having contact with the blood of someone who has HIV. This could be having a blood transfusion from someone who is infected with HIV

From a mother who has HIV to her baby: HIV can pass to the baby during pregnancy, during the birth of the baby, or through breast-feeding. Only about one in three babies born to HIV-positive mothers get HIV.

Receiving an injection from an unsterilized needle that was previously used by someone with HIV.

Heterosexual transmission is the route by which most people with AIDS have become infected with HIV worldwide
This category of AIDS cases is also among the most rapidly increasing.

Investigation and Diagnosis of HIV

Who needs HIV testing ?
- sexually active
* ≥3 sexual partners in the last 12 months
-a male who has had sex with another male
-Drug addicts who take drugs by injection
*sharing needles and/or other equipment.
-STD patients
-Pregnant woman / woman who wants to make sure she is not infected by HIV before getting pregnant
-Patients who received a blood transfusion prior to 1985, or a sexual partner received a transfusion and later tested positive for HIV
-Health care worker with direct exposure to blood on the job

HIV Antibody Testing :
-Detects HIV antibodies in blood or other body fluids
-can be detected about 3 to 8 weeks after exposure to the virus
-Sample collected for testing:
*Blood
>inserting a needle into a vein in the arm
*Oral sample
>swab completely once around the outer part of the upper and lower gums
*Urine
-Screening tests available :
*ELISA
*Confirmatory test : Western Blot
*Home collection kit
-If you are tested too soon, result may be negative despite the fact that you are infected (false negative).
*may be tested using a p24 antigen test that can detect actual viral protein in the blood 1 to 3-4 weeks after exposure or an HIV RNA test (viral load) 
>detects the presence of the virus

ELISA - (Enzyme-linked Immunosorbent Assay Test)
-A common serological test
-For the presence of particular antigens or antibodies (Serum)
-Direct and indirect
*Direct : Employs monoclonal antibodies to detect the presence of particular antigens in a sample
*Indirect :To determine the presence of specific antibody (eg.HIV antibodies)

Indirect ELISA :
Appropriate antigen is first absorbed to the walls of a microtiter plate.
If serum contains antibodies against the antigens – bind to antigens (form complex)
Rinsing removes any antibodies that do not specifically attach to antigen
Addition of an antibody-enzyme conjugate
*Enzyme-conjugated anti-human IgG antibodies as reporter.
Enzyme-conjugated antibody will bind to the complex
Sample is rinsed again to remove any unbound antibodies
Substrate for the enzyme is added
Colour change – indicates the presence of antibodies that react against the antigens

-If test is taken right after the exposure and the result is negative
(False positive)
-If result is negative after “window period”
(HIV negative)
-If result is positive
*Confirmatory test is required
> WESTERN BLOT TEST

Western Blot Test :
HIV proteins are extracted.
Proteins are electrophoresed into a gel.
Proteins migrate through the gel when they are separated based upon size and charge. smaller proteins migrate through the gel faster than larger proteins.
Sufficiently separated proteins can be transferred to a solid membrane for WB analysis.
electric current is applied to the gel
All sites on the membrane which do not contain blotted protein from the gel can then be non-specifically "blocked"
*so that antibody (serum) will not non-specifically bind to them
*causing a false positive result.
membrane is cut into strips
*to facilitate testing of a large number of samples for antibodies directed against the blotted protein (antigen).
Procedure continues similar to ELISA.

Home Collection Kit :
-Approved by the US Food and Drug Administration (FDA)
-Take a sample of your blood from a finger at home and mail it to a testing center
-Hear your results later over the phone, along with appropriate counseling.

HIV Viral Load :
-the amount (viral load) of RNA (nucleic acid) of the human immunodeficiency virus (HIV) in blood.
-It is measured during the “window period” before the antibodies present
-Sample is collected from blood
*drawn by needle from a vein in your arm
-Can be measured after the therapy has started
*To evaluate whether the therapy is effective
-Test result:
*tests are reported as the number of HIV copies in a milliliter (copies/mL) of blood
*high viral load: from 5,000 to 10,000 copies/mL
*low viral load: between 40 to 500 copies/mL
>risk of disease progression is low.
-Tests available :
*p24 antigen count testing
>Followed by CD4 count
*Polymerase Chain Reaction (PCR)

p24 Antigen Count Test :
-p24 is a protein "shell" on the surface of HIV.
-help diagnose HIV viral protein in blood during early HIV infection.
*before HIV antibody is produced
-Result is positive : 1 week to 3-4 weeks after infection with HIV.
-Not detected until about 1 week after infection with HIV
*the virus haven’t multiplied to sufficient numbers to be detected.
-About 3-8 weeks after initial exposure, antibodies are produced.
*results of the p24 test will usually be negative although the person may be infected with HIV.
*antibodies bind to the p24 protein
>P24 protein no longer be detected in the blood.
 *HIV antibody test is used
-Later in the course of HIV, p24 protein become detectable if the disease is untreated.

CD4 Count :
-measurement of how many functional CD4 T-cells are circulating in the blood.
-CD4 cells - host cells that aid HIV in replication.
*HIV attaches to the CD4 cells
*allowing the virus to enter and infect the CD4 cells
*Damage the CD4 cells
-The lower the absolute CD4 count, the weaker the immune system.
-is measured by a simple blood test
-is reported as the number of CD4 cells per cubic millimeter of blood.
-Normal value :
*600 to 1200 cells per cubic millimter of blood
-Between 600 and 350 :
*In an HIV+ person, this range is considered "very good".
-Between 350 and 200 :
*The immune system is weakened
*HIV+ person may be at increased risk for infection and illness.
-Less that 200 :
*The immune system is severely weakened
*HIV+ person is at a much greater risk of opportunistic infections.

Prevention

Effective HIV prevention intervention includes

• Condom use
  Condoms, when used correctly and consistently, are highly effective in preventing HIV and other sexually transmitted infections (STIs). A large body of scientific evidence shows that male latex condoms have an 80% or greater protective effect against the sexual transmission of HIV and other STIs. Latex condoms are the best way to keep from getting HIV during sex. If you or your partner is allergic to latex, there are condoms made of polyurethane that can protect against HIV, too. But natural membrane condoms, also called lambskin condoms, do not prevent HIV because the virus can pass through them. If a man can’t or won’t use a condom, a woman can use the Reality female condom. It may protect against HIV, but it’s not as good as the latex condom a man uses. Do not use a Reality female condom along with a male condom. Both condoms will not stay in place when used together

• Male circumcision
  Male circumcision is the surgical removal of some or all of the foreskin (or prepuce) from the penis. This can reduce the risk of HIV infection in heterosexual men. However, the individual must continue to use other forms of protection(male condoms/female condoms).

• Provision of clean injecting equipment

• Opioid substitution therapy
  Opioid: analgesic that works by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract
  Reduce transmission of blood-borne viruses

• Treatment of sexually transmitted infections
  Sexually transmitted infections (STI) have been shown to be important cofactors in the transmission and acquisition of HIV infection. For example, in Rakai, Uganda, research has shown an emergence of genital herpes simplex virus (HSV) in areas with mature HIV epidemics (i.e., areas with a high prevalence of HIV). Investigators found a nearly fivefold association of HSV with HIV-1 acquisition
  Genital ulcers, such as those associated with HSV-2, are potent cofactors in both HIV transmission and acquisition

• HIV testing and counselling
• A set of interventions to prevent mother-to-child transmission of HIV
• Sex education

To educate youth and society of

• Abstinence
• Use of condoms
  In Malaysia
  Reproduction – Form 3
  E.g. in Thailand
  “Condom King”
  Captain Mandela- HIV computer game
  

In health care settings, transmission of HIV can be prevented through

• Primary prevention measures such as blood safety, standard precautions, injection safety, and safe waste disposal

Standard precautions:

• Handwashing (or using an antiseptic handrub)
• Gloves, Masks, goggles, face masks, Gowns, Linen
• Patient care equipment
• Environmental cleaning
• Sharps
• Patient resuscitation
• Patient placement
• Use physical barriers (protective goggles, face masks and aprons)
• Use antiseptic agents for cleansing the skin or mucous membrane
• Use safe work practices such as not recapping or bending needles,
• Safely dispose of infectious waste materials to protect those who
  handle them and prevent injury or spread of infection to the
  community.
• Process instruments, gloves and other items after use by first
  decontaminating and thoroughly cleaning them, then either sterilizingor high-level disinfecting them using the recommended procedures

• Secondary prevention measures, such as post-exposure prophylaxis for occupational or certain non-occupational exposures to HIV such as in health-care settings, post-rape, and in case of condom breakage.

o Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure, either occupationally or through sexual intercourse.
o If you are within 72 hours of an incident of possible exposure to HIV, ask for PEP (Post Exposure Prophylaxis) treatment
o PEP treatment can help stop you becoming infected with the virus after you have been exposed to HIV. The sooner treatment is begun the higher the probability the treatment will be effective

In addition, there is increasing evidence indicating that

• ART programmes can be implemented in a way that emphasizes HIV prevention
• Current research on new prevention technologies such as microbicides, topical and oral antiretroviral pre-exposure prophylaxis in preventing the transmission of HIV and AIDS vaccines is ongoing.

Microbicides: compounds that can be applied inside the vagina or rectum to protect against sexually transmitted infections (STIs) including HIV.

HIV prevention - combination behavioural change approach has been
labelled as ABC—i.e.,

>Abstinence, including delay of sexual initiation or debut

>Being safer by being faithful to one’s partner or reducing the number of sexual partners

>correct and consistent Condom use

References:

1. Centers World Health Organization
http://www.who.int/hiv/topics/prevention/en/

2. Malaysian Aids Council
http://www.mac.org.my/hmtct.htm

3. Food and Drug Administration
http://www.fda.gov/opacom/lowlit/aids.pdf

4. Centers for Disease Control and Prevention
http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm
http://www.reproline.jhu.edu/english/4morerh/4ip/IP_manual/02_StandardPrecaution.pdf