Chapter 18:Chapter 18:

AIDS & Other Immune DisordersAIDS & Other Immune Disorders

Immune System DisordersImmune System DisordersHypersensitivity (Allergy)Hypersensitivity (Allergy): An abnormal : An abnormal

response to antigens.response to antigens.

Four Types of Hypersensitivity Reactions:Four Types of Hypersensitivity Reactions: Type I (Anaphylactic) ReactionsType I (Anaphylactic) Reactions Type II (Cytotoxic) ReactionsType II (Cytotoxic) Reactions Type III (Immune Complex) ReactionsType III (Immune Complex) Reactions Type IV (Cell-Mediated) ReactionsType IV (Cell-Mediated) Reactions

Type I (Anaphylactic) ReactionsType I (Anaphylactic) Reactions Occur within minutes of exposure to antigenOccur within minutes of exposure to antigen Antigens combine with IgE antibodiesAntigens combine with IgE antibodies IgE binds to mast cells and basophils, causing IgE binds to mast cells and basophils, causing

them to undergo them to undergo degranulationdegranulation and release and release several mediators:several mediators: HistamineHistamine: Dilates and increases permeability of : Dilates and increases permeability of

blood vessels (swelling and redness), increases blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle mucus secretion (runny nose), smooth muscle contraction (bronchi). contraction (bronchi).

ProstaglandinsProstaglandins: Contraction of smooth muscle of : Contraction of smooth muscle of respiratory system and increased mucus secretion.respiratory system and increased mucus secretion.

LeukotrienesLeukotrienes: Bronchial spasms.: Bronchial spasms.

Anaphylactic shockAnaphylactic shock: Massive drop in blood : Massive drop in blood pressure. Can be fatal in minutes.pressure. Can be fatal in minutes.

Type I Anaphylactic Reaction

Mast Cells and the Allergic Response

Type II (Cytotoxic) ReactionsType II (Cytotoxic) Reactions Involve activation of Involve activation of complementcomplement by IgG or by IgG or

IgM binding to an antigenic cell.IgM binding to an antigenic cell. Antigenic cell is lysed.Antigenic cell is lysed. Transfusion reactions:Transfusion reactions:

ABO Blood group systemABO Blood group system: Type O is universal : Type O is universal donor. Incompatible donor cells are lysed as they donor. Incompatible donor cells are lysed as they enter bloodstream.enter bloodstream.

Rh Blood Group SystemRh Blood Group System: 85% of population is Rh : 85% of population is Rh positive. Those who are Rh negative can be positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.sensitized to destroy Rh positive blood cells.

• Hemolytic disease of newbornHemolytic disease of newborn: Fetal cells are destroyed : Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.by maternal anti-Rh antibodies that cross the placenta.

Hemolytic Disease of the Newborn-Rh Incompatability

Type III (Immune Complex) ReactionsType III (Immune Complex) Reactions Involve reactions against Involve reactions against solublesoluble antigens antigens

circulating in serum.circulating in serum. Usually involve IgA antibodies.Usually involve IgA antibodies. Antibody-Antigen immune complexes are Antibody-Antigen immune complexes are

deposited in organs, activate complement, and deposited in organs, activate complement, and cause inflammatory damage.cause inflammatory damage. GlomerulonephritisGlomerulonephritis: Inflammatory kidney : Inflammatory kidney

damage.damage.

Occurs with slightly high antigen-antibody Occurs with slightly high antigen-antibody ratio is present.ratio is present.

Immune Complex Mediated Hypersensitivity

Type IV (Cell-Mediated) ReactionsType IV (Cell-Mediated) Reactions Involve reactions by TInvolve reactions by TDD memory cells. memory cells.

First contact sensitizes person.First contact sensitizes person. Subsequent contacts elicit a reaction.Subsequent contacts elicit a reaction.

Reactions are Reactions are delayeddelayed by one or more days by one or more days (delayed type hypersensitivity).(delayed type hypersensitivity). Delay is due to migration of macrophages and T Delay is due to migration of macrophages and T

cells to site of foreign antigens.cells to site of foreign antigens.

Reactions are frequently displayed on the skin: Reactions are frequently displayed on the skin: itching, redness, swelling, pain. itching, redness, swelling, pain.

• Tuberculosis skin testTuberculosis skin test

• Poison ivyPoison ivy

• Metals (Nickel)Metals (Nickel)

• Latex in gloves and condoms (3% of health care workers)Latex in gloves and condoms (3% of health care workers)

Anaphylactic shock may occur.Anaphylactic shock may occur.

Allergic Contact Dermatitis Response to Poison Ivy Hapten

Autoimmune DiseasesAutoimmune Diseases Loss of self-toleranceLoss of self-tolerance leads to production leads to production

of antibodies or T cells that react against of antibodies or T cells that react against one’s own antigens.one’s own antigens.

Immune system response to self antigens Immune system response to self antigens causes damage to organs. causes damage to organs.

Three types of autoimmune disorders:Three types of autoimmune disorders: Cytotoxic (Type II reactions)Cytotoxic (Type II reactions) Immune complex (Type III reactions)Immune complex (Type III reactions) Cell-mediated (Type IV reactions)Cell-mediated (Type IV reactions)

Autoimmune DiseasesAutoimmune DiseasesA. Type II (Cytotoxic) Autoimmune ReactionsA. Type II (Cytotoxic) Autoimmune ReactionsInvolve Involve antibodyantibody reactions to cell surface molecules, reactions to cell surface molecules,

withoutwithout cytotoxic destruction of cells. cytotoxic destruction of cells. Grave’s DiseaseGrave’s Disease: :

Antibodies attach to receptors on thyroid gland and Antibodies attach to receptors on thyroid gland and stimulate production of thyroid hormone.stimulate production of thyroid hormone.

Symptoms: Goiter (enlarged thyroid) and bulging Symptoms: Goiter (enlarged thyroid) and bulging eyes.eyes.

Treatment: Removal of thyroid with radioactive Treatment: Removal of thyroid with radioactive Iodine and supplementation with thyroid hormoneIodine and supplementation with thyroid hormone..

Myasthenia gravisMyasthenia gravis: : Progressive muscle weakness. Antibodies block Progressive muscle weakness. Antibodies block

acetylcholine receptors at neuromuscular synapse.acetylcholine receptors at neuromuscular synapse. Affects 25,000 Americans (mainly women).Affects 25,000 Americans (mainly women). Today most patients survive when treated with Today most patients survive when treated with

drugs or immunosuppressants.drugs or immunosuppressants.

Grave’s Disease Myasthenia Gravis

Source: www.mo-media.com Source: meds.queenssu.ca

Autoimmune DiseasesAutoimmune DiseasesB. Type III (Immune Complex) Autoimmune B. Type III (Immune Complex) Autoimmune

ReactionsReactions Systemic Lupus ErythematosusSystemic Lupus Erythematosus: :

Affects about 200,000 Americans (90% women). Affects about 200,000 Americans (90% women). Name derived from red skin rash on face. Name derived from red skin rash on face. Autoantibodies react against DNA, blood cells, Autoantibodies react against DNA, blood cells,

neurons, and other tissues. neurons, and other tissues. When cells die, When cells die, immune complexesimmune complexes form and deposit form and deposit

under skin, joints, in kidneys, blood vessels, and under skin, joints, in kidneys, blood vessels, and central nervous system.central nervous system.

Inflammation interferes with normal function of Inflammation interferes with normal function of these sites (arthritis, rash, kidney damage).these sites (arthritis, rash, kidney damage).

Most patients die from kidney damage.Most patients die from kidney damage. No cure. Symptoms treated with anti-inflammatory No cure. Symptoms treated with anti-inflammatory

and immunosuppressive drugs.and immunosuppressive drugs.

Systemic Lupus Erythematosus-Acute Cutaneous FormButterfly rash seen in up to 50% of patients

Source: Clinical Dermatology, 3rd Edition, T.P. Habif

Systemic Lupus Erythematosus-Cutaneous Form

Autoimmune DiseasesAutoimmune DiseasesB. Type III (Immune Complex) Autoimmune B. Type III (Immune Complex) Autoimmune

Reactions (Continued)Reactions (Continued) Rheumatoid ArthritisRheumatoid Arthritis: :

Affects about 2 million Americans (70%+ women). Affects about 2 million Americans (70%+ women). Cause unknown, but Cause unknown, but microbial mimicrymicrobial mimicry may be may be

involved.involved. IgM autoantibodies (IgM autoantibodies (rheumatoid factorsrheumatoid factors) against ) against

IgG form complexes in joint, leading to IgG form complexes in joint, leading to inflammation and cartilage damage. inflammation and cartilage damage.

Often causes finger and joint deformities.Often causes finger and joint deformities. No cure. Symptoms treated with anti-inflammatory No cure. Symptoms treated with anti-inflammatory

(aspirin) and immunosuppressive drugs. Physical (aspirin) and immunosuppressive drugs. Physical therapy keeps joints movable. Surgical replacement therapy keeps joints movable. Surgical replacement of joints may be necessary.of joints may be necessary.

Rheumatoid Arthritis

Source: www.csmc.edu

Autoimmune DiseasesAutoimmune DiseasesC. Type IV (Cell-Mediated) Autoimmune Reactions C. Type IV (Cell-Mediated) Autoimmune Reactions

Insulin-dependent (Type I or Juvenile) Diabetes MellitusInsulin-dependent (Type I or Juvenile) Diabetes Mellitus: : Affects 2 million people in United States.Affects 2 million people in United States. Usually develops before the age of 15. Usually develops before the age of 15. Makes up about 10% of all diabetes cases. Makes up about 10% of all diabetes cases. 35,000 people die every year from complications 35,000 people die every year from complications

(gangrene, kidney and cardiovascular disease, (gangrene, kidney and cardiovascular disease, dehydration, and nerve damage).dehydration, and nerve damage).

Characterized by insufficient insulin production due to Characterized by insufficient insulin production due to immunological destruction of insulin-secreting cells of immunological destruction of insulin-secreting cells of the pancreas by T cells. the pancreas by T cells.

Treatment: Patients require daily insulin injections (or Treatment: Patients require daily insulin injections (or pump) to maintain adequate blood glucose levels.pump) to maintain adequate blood glucose levels.

Multiple Sclerosis T cells and macrophages attack myelin sheath of neurons in brain, T cells and macrophages attack myelin sheath of neurons in brain,

spinal cord, and optic nerves.spinal cord, and optic nerves. Symptoms: Symptoms:

Fatigue, muscle weakness, sexual, bladder and bowel problemsFatigue, muscle weakness, sexual, bladder and bowel problems Sensations of pain, numbness, tingling, burning, itching, and electrical shockSensations of pain, numbness, tingling, burning, itching, and electrical shock Visual changes (blurred, double or moving field of vision, floaters) or blindnessVisual changes (blurred, double or moving field of vision, floaters) or blindness Dizziness, vertigo, headaches, slurred speech, difficulty swallowingDizziness, vertigo, headaches, slurred speech, difficulty swallowing Depression, mood changes, confusion, seizures, thinking and memory problemsDepression, mood changes, confusion, seizures, thinking and memory problems Paralysis, limping, muscle cramps, spasticity (involuntary spasms), tremors Paralysis, limping, muscle cramps, spasticity (involuntary spasms), tremors

Epidemiology: Epidemiology: In U.S. 350,000 people diagnosed with MS. In U.S. 350,000 people diagnosed with MS. Up to 4X more people may be undiagnosed or have “Silent MS”. Up to 4X more people may be undiagnosed or have “Silent MS”. More common in females, northern european background. Residents of tropics “protected” More common in females, northern european background. Residents of tropics “protected”

(Vitamin D exposure?).(Vitamin D exposure?). First episode between 15-50 years; may occur in children or older adults.First episode between 15-50 years; may occur in children or older adults.

Relapsing-remitting form: 85% of cases. Attacks followed by recovery Relapsing-remitting form: 85% of cases. Attacks followed by recovery and long periods of remission; decline over several yrs.and long periods of remission; decline over several yrs.

Treatment: No cure. Beta interferon reduces frequency and severity of Treatment: No cure. Beta interferon reduces frequency and severity of relapses. Also corticosteroids for acute attacks.relapses. Also corticosteroids for acute attacks.

Source: www.nature.com

Multiple Sclerosis: Brain Lesions on MRI

Source: www.csmc.edu

Celiac Disease Celiac disease is the Celiac disease is the most commonmost common and most under-diagnosed and most under-diagnosed

hereditary autoimmune disease in the United States. Affects hereditary autoimmune disease in the United States. Affects approximately 1 in 100 people. 97% are undiagnosed (average 9 approximately 1 in 100 people. 97% are undiagnosed (average 9 years for diagnosis).years for diagnosis).

Macrophages and antibodies destroy intestinal villi and microvilli Macrophages and antibodies destroy intestinal villi and microvilli when eat when eat glutengluten (protein in wheat, rye, barley, oats). (protein in wheat, rye, barley, oats).

Presence of gluten (gliadin) triggers damage to lining of small Presence of gluten (gliadin) triggers damage to lining of small intestine. Causes poor digestion and absorption of food.intestine. Causes poor digestion and absorption of food.

Symptoms:Symptoms: Digestive: Gas, bloating, indigestion, diarrhea, reflux, vomiting, constipation Digestive: Gas, bloating, indigestion, diarrhea, reflux, vomiting, constipation Consequences of malabsorption: Malnutrition, anemia, weight loss, “failure to Consequences of malabsorption: Malnutrition, anemia, weight loss, “failure to

thrive, vitamin deficiency, fatigue, osteoporosis, muscle atrophy.thrive, vitamin deficiency, fatigue, osteoporosis, muscle atrophy. Inflammation and Autoimmune Disease: Dermatitis, type I diabetes, fibromyalgia, Inflammation and Autoimmune Disease: Dermatitis, type I diabetes, fibromyalgia,

irritable bowel syndrome, eczema, psoriasis, vitiligoirritable bowel syndrome, eczema, psoriasis, vitiligo Other Complications: Infertility, cancer (thyroid, intestine, esophagus, melanoma, Other Complications: Infertility, cancer (thyroid, intestine, esophagus, melanoma,

non-Hodgkin’s lymphoma), peripheral neuropathy, seizures, migraines, dementia, non-Hodgkin’s lymphoma), peripheral neuropathy, seizures, migraines, dementia, cardiomyopathy (heart failure and arrythmia).cardiomyopathy (heart failure and arrythmia).

Treatment: No cure, life-long condition. Prevention by stopping Treatment: No cure, life-long condition. Prevention by stopping all gluten consumption (Gluten-free diet).all gluten consumption (Gluten-free diet).

Celiac Disease: Small Intestine Damage

Source: www.celiacdiseasecenter.columbia.edu

Acquired Immunodeficiency Acquired Immunodeficiency Syndrome (AIDS)Syndrome (AIDS)

HistoryHistory 1950s1950s: Blood samples from Africa have HIV : Blood samples from Africa have HIV

antibodies.antibodies. 19761976: First : First knownknown AIDS patient died.AIDS patient died. 19801980: First human retrovirus isolated (HTLV-1).: First human retrovirus isolated (HTLV-1). 19811981: First reports of “Acquired Immuno-: First reports of “Acquired Immuno-

deficiency Syndrome” in Los Angeles.deficiency Syndrome” in Los Angeles. 19831983: Virus first isolated in France: Virus first isolated in France ( (LAVLAV).). 19841984: Virus isolated in the U.S. (called: Virus isolated in the U.S. (called HTLV-IIIHTLV-III

and AIDS-Related Virus,and AIDS-Related Virus, ARVARV).). 19851985: Development and implementation of : Development and implementation of

antibody test to screen blood donors.antibody test to screen blood donors.

Acquired Immunodeficiency Acquired Immunodeficiency Syndrome (AIDS)Syndrome (AIDS)

History (Continued)History (Continued) 19861986: : Consensus name Human Immunodeficiency Consensus name Human Immunodeficiency

Virus (HIV-1). Virus (HIV-1). Related virus (HIV-2) identified.Related virus (HIV-2) identified.

19921992: : AIDS becomes the leading cause of death AIDS becomes the leading cause of death among adults ages 25-44 in the U.S.among adults ages 25-44 in the U.S.

1997: 1997: Mortality rates of AIDS starts to decline due Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails.to the introduction of new drug cocktails.

20052005: World Health Organization predicts up to : World Health Organization predicts up to 40 million infected individuals. More than 25 40 million infected individuals. More than 25 million have already died.million have already died.

AIDS: A Leading Cause of Death Among People Aged 25-44 years in U.S.

0

5

10

15

20

25

30

35

40

1982 1986 1990 1994

AIDS

Accidents

Cancer

Homicide

Deaths per 100,000 people aged 25-44 years

People Living with HIV/AIDS by End of 2005

North America950,000

(0.6%)*

Latin America 1.5 million (0.6%)*

Western Europe560,000

(0.3%)*

East Europe & Central Asia1’000,000

(0.6%)*

Sub-Saharan Africa28.5 million

(8.8%)*

North Africa & Middle East

500,000(0.3%)*

Australia & New Zealand 15,000 (0.1%)*

South/South East Asia5.6 million

(0.6%)*

East Asia & Pacific1’000,000

(0.1%)*

Total: 40 million people*: Percentage of infected 15-49 year olds per region

Caribbean420,000

(2.4%)*

Structure of the Human Immunodeficiency Virus HIV is a Retrovirus

Life Cycle of HIVLife Cycle of HIV1. Attachment: 1. Attachment: Virus binds to surface Virus binds to surface

molecule (CD4) of T helper cells and molecule (CD4) of T helper cells and macrophages.macrophages. CoreceptorsCoreceptors: : Required for HIV infection. Required for HIV infection. CXCR4CXCR4 and and CCR5CCR5 mutants are resistant to mutants are resistant to

infection.infection.

2. Fusion2. Fusion: Viral envelope fuses with cell : Viral envelope fuses with cell membrane, releasing contents into the membrane, releasing contents into the cell.cell.

HIV Life Cycle: Attachment Requires CD4 Receptor plus a Coreceptor

Life Cycle of HIVLife Cycle of HIV3. Reverse Transcription3. Reverse Transcription: : Viral RNA is Viral RNA is

converted into DNA by unique enzyme converted into DNA by unique enzyme reverse transcriptasereverse transcriptase..

Reverse transcriptaseReverse transcriptaseRNA ---------------------> DNARNA ---------------------> DNA

Reverse transcriptase is the target of Reverse transcriptase is the target of several HIV drugs: AZT, ddI, and ddC.several HIV drugs: AZT, ddI, and ddC.

HIV Life Cycle: Reverse Transcriptase Converts RNA into DNA

Life Cycle of HIVLife Cycle of HIV4. Integration4. Integration: Viral DNA is inserted into host cell : Viral DNA is inserted into host cell

chromosome by unique enzyme chromosome by unique enzyme integraseintegrase. . Integrated viral DNA may remain latent for years Integrated viral DNA may remain latent for years and is called a and is called a provirusprovirus..

5. Replication5. Replication: Viral DNA is transcribed and RNA : Viral DNA is transcribed and RNA is translated, making viral proteins. is translated, making viral proteins.

Viral genome is replicated.Viral genome is replicated.

6. Assembly:6. Assembly: New viruses are made. New viruses are made.

7. Release:7. Release: New viruses bud through the cell New viruses bud through the cell membrane.membrane.

HIV Life Cycle: Latent versus Active Infection

HIV Life Cycle: Latent versus Active Infection in Macrophages

AIDS Associated Disease CategoriesAIDS Associated Disease Categories1. Gastrointestinal: 1. Gastrointestinal: Cause most of illness and death Cause most of illness and death

of late AIDS. of late AIDS.

SymptomsSymptoms::

DiarrheaDiarrhea

Wasting (extreme weight loss)Wasting (extreme weight loss)

Abdominal painAbdominal pain

Infections of the mouth and esophagus. Infections of the mouth and esophagus.

PathogensPathogens: : CandidaCandida albicansalbicans, cytomegalovirus, , cytomegalovirus,

Microsporidia, and Cryptosporidia.Microsporidia, and Cryptosporidia.

African AIDS patient with slim diseaseSource: Tropical Medicine and Parasitology, 1997

Wasting in an AIDS Patient

Opportunistic Oral Yeast Infection by Candida albicans in an AIDS Patient

Source: Atlas of Clinical Oral Pathology, 1999

AIDS Associated Disease CategoriesAIDS Associated Disease Categories2. Respiratory: 2. Respiratory: 70% of AIDS patients develop 70% of AIDS patients develop

serious respiratory problems.serious respiratory problems.

Partial list of respiratory problems associated with AIDS: Partial list of respiratory problems associated with AIDS:

BronchitisBronchitis

PneumoniaPneumonia

TuberculosisTuberculosis

Lung cancerLung cancer

SinusitisSinusitis

PneumonitisPneumonitis

Chest X-Ray of AIDS Patient with Tuberculosis

AIDS Associated Disease CategoriesAIDS Associated Disease Categories3. Neurological:3. Neurological: Opportunistic diseases and Opportunistic diseases and

tumors of central nervous system.tumors of central nervous system.

Symptoms many include: Headaches, peripheral Symptoms many include: Headaches, peripheral

nerve problems, and nerve problems, and AIDS dementia complexAIDS dementia complex

(Memory loss, motor problems, difficulty (Memory loss, motor problems, difficulty

concentration, and paralysis).concentration, and paralysis).

AIDS Associated Disease CategoriesAIDS Associated Disease Categories4. Skin Disorders:4. Skin Disorders: 90% of AIDS patients develop 90% of AIDS patients develop

skin or mucous membrane disorders.skin or mucous membrane disorders. Kaposi’s sarcomaKaposi’s sarcoma

• 1/3 male AIDS patients develop KS1/3 male AIDS patients develop KS• Most common type of cancer in AIDS patientsMost common type of cancer in AIDS patients

Herpes zoster (shingles)Herpes zoster (shingles) Herpes simplexHerpes simplex ThrushThrush Invasive cervical carcinomaInvasive cervical carcinoma

5. Eye Infections: 5. Eye Infections: 50-75% patients develop eye 50-75% patients develop eye conditions.conditions. CMV retinitisCMV retinitis ConjunctivitisConjunctivitis Dry eye syndromeDry eye syndrome

Extensive tumor lesions of Kaposis’s sarcoma in AIDS patient.Source: AIDS, 1997

Chronic Herpes Simplex infection with lesions on tongue and lips.Source: Atlas of Clinical Oral Pathology, 1999.

Non-Hodgkin’s Lymphoma & ascites in AIDS patientSource: Tropical Medicine and Parasitology, 1997

Drugs Against HIVDrugs Against HIV Reverse Transcriptase Inhibitors: Reverse Transcriptase Inhibitors: Competitive Competitive

enzyme inhibitors. Example: AZT, ddI, ddC.enzyme inhibitors. Example: AZT, ddI, ddC. Protease InhibitorsProtease Inhibitors: Inhibit the viral proteases. : Inhibit the viral proteases.

Prevent viral maturation.Prevent viral maturation. Problem with individual drug treatments: Problem with individual drug treatments:

Resistance.Resistance. Drug CocktailsDrug Cocktails: A combination of:: A combination of:

One or two reverse transcriptase inhibitorsOne or two reverse transcriptase inhibitors One or two protease inhibitors.One or two protease inhibitors.

Drug cocktails have been very effective in Drug cocktails have been very effective in suppressing HIV replication and prolonging the suppressing HIV replication and prolonging the life of HIV infected individuals, but long term life of HIV infected individuals, but long term effectiveness is not clear.effectiveness is not clear.

Stages of HIV Infection

Antibody Levels, T Cell Counts, and HIV Concentration After Infection

Transmission of AIDS (Worldwide)Transmission of AIDS (Worldwide)1.1. Sexual contact with infected individual:Sexual contact with infected individual: All All

forms of sexual intercourse (homosexual and forms of sexual intercourse (homosexual and heterosexual). 75% of transmission.heterosexual). 75% of transmission.

2. Sharing of unsterilized needles by 2. Sharing of unsterilized needles by intravenous drug users and unsafe medical intravenous drug users and unsafe medical practices: practices: 5-10% of transmission. 5-10% of transmission.

3. Transfusions and Blood Products:3. Transfusions and Blood Products: Hemophiliac population was decimated in Hemophiliac population was decimated in 1980s. Risk is low today. 3-5% of 1980s. Risk is low today. 3-5% of transmission. transmission.

4. Mother to Infant (Perinatal):4. Mother to Infant (Perinatal): 25% of 25% of children become infected in utero, during children become infected in utero, during delivery, or by breast-feeding (with AZT only delivery, or by breast-feeding (with AZT only 3%). 5-10% of transmission. 3%). 5-10% of transmission.

HIV Transmission in United States and Rest of the World

Perinatal Transmission of AIDSSource: Tropical Medicine and Parasitology, 1997