infectious diseases

AIDS

AIDS
Acquired ImmunoDeficiency Syndrome

Definition

36.9 million people globally were living with HIV (end 2014) 2 million people became newly infected with HIV (end 2014) 1.21 million people died from AIDS-related illnesses (end 2014). New HIV infections have fallen by 35% since 2000. Worldwide, 2 million people became newly infected with HIV in 2014, down from 3.1 million in 2000.
INTRODUCTION

VIROLOGY

HIV
Human Immunodeficiency Virus



HIV1: Commonest and more serious than. This form of HIV has spread throughout the world. HIV2: is less potent that HIV-1, is found predominantly in West Africa.
HIV is a retrovirus (RNA)


The virus contains 2 main enzymes: 1. Transcriptase E: important for viral replication (viral copies). 2. Protease: important for protein synthesis (viral structure).

CELLS AFFECTED

The virus infects T-lymphocytes (CD4 cell or T-Helper) Healthy adults usually have CD4+ T-cell counts (Helper) of 1,000 or more. Aids and some HIV sufferers have less than 200 CD4+ T-cells with abnormal function (Cellular immunity)


Other cells that are also affected Monocyte-macrophages (Phagocytic cells). B- lymphocytes function (Ab making cells). Follicular dendritic cells microglial cells in the central nervous system.

Transmission

HIV is present in blood, semen and other body fluids such as breast milk and saliva. Exposure to infected fluid leads to a risk of contracting infection, which is dependent on the integrity of the exposed site, the type and volume of body fluid, and the viral load.

1. sexual (man to man, heterosexual and oral), 2. parenteral A. blood or blood product recipients. B. injection drug-users C. those experiencing occupational injury. 3. vertical.
The modes of spread

Sexual Contact

PARENTERAL


Around 70% of patients with haemophilia A and 30% of those with haemophilia B had been infected through contaminated blood products by the time HIV antibody screening was adopted in the USA and Europe in 1985. In developed countries, because of routine antibody screening, the likelihood of acquiring HIV from blood products is now less than 1:500000 and arises from donors in the seroconverting phase of infection.

3. The WHO estimates that because of the lack of adequate screening facilities in resource-poor countries, 5-10% of blood transfusions globally are with HIV-infected blood. 4. There have been approximately 100 definite and 200 possible cases of HIV acquired occupationally in health-care workers in (some) developing countries.

5. Infection related to health-care settings is substantially higher in (some) developing nations, where it is estimated that 40% of syringes/needles used in injections are reused without sterilisation.

HIV has been detected in the saliva of infected individuals, however, no evidence exists that the virus is spread by contact with saliva. Tests show saliva has natural compounds that inhibit the infectiousness of HIV. No evidence has been found that the virus is spread to others through saliva such as by kissing. HIV has not been found to spread through: feces, sweat, tears and urine.

Vertical transmission

The transmission risk after exposure is: Over 90% for blood or blood products. 15-40% for the vertical route. 0.5-1.0% for injection drug use. 0.2-0.5% for genital mucous membrane spread Under 0.1% for non-genital mucous membrane spread.

1. In the USA and northern Europe, the epidemic has predominantly been in Homosexuals. 2. whereas in southern and Eastern Europe, Vietnam, Malaysia, North-east India and China the incidence has been greatest in injection drug-users. 3. In Africa, the Caribbean and much of South-east Asia the dominant routes of transmission are heterosexual and from mother to child (vertical).



Laboratory serology tests


Enzyme-linked immunosorbent assay (ELISA) 1. Is a screening test for HIV infection. 2. 50% of ELISA tests are positive within 3 weeks after HIV transmission. 3. 95% are positive within 6 weeks after transmission. Sensitivity > 99.9%. 4. to avoid false-positive results, repeatedly reactive results must be confirmed with Western blot.


Western blot: Is a confirmatory test for HIV. It is highly Specific when combined with ELISA (> 99.99%). Indeterminate results with: 1. early HIV infection. 2. HIV-2 infection. 3. autoimmune disease. 4. pregnancy. 5. recent tetanus toxoid administration.


If a person is highly likely to be infected with HIV and yet both tests are negative, a doctor may test for the presence of HIV itself in the blood (PCR), with a repeat antibody testing at a later date, when antibodies to HIV are more likely to have developed.

PCR (polymerase chain reaction) test should also be carried out on: 1. Anyone who had a blood transfusion before 1985 2. Anyone who has had unprotected sex with an infected person 3. Infants of infected mothers (Maternal anti bodies are present so give false positive ELIZA or Western blot test).

Complete blood count

1. Anemia, neutropenia, and thrombocytopenia common with advanced HIV infection. 2. Absolute CD4 lymphocyte count is the most widely used predictor of HIV progression (normal count is >500cells/uL). Risk of progression to an AIDS opportunistic infection or malignancy is high with CD4 < 200 cells/uL. 3. CD4 lymphocyte percentage which may be more reliable than the CD4 count. Risk of progression to an AIDS opportunistic infection or malignancy is high with percentage < 20%.

HIV viral load tests

1. These tests measure the amount of actively replicating HIV virus. 2. Correlate with disease progression and response to antiretroviral drugs. 3. Best tests available for diagnosis of acute HIV infection; 4. however, false positives are common, especially when the viral load is low.

CLINICAL PICTURE

Following infection with HIV, a latent period (IP) of several Ws during which the patient is asymptomatic and usually seronegative. Seropositive stage: Seroconversion (primary acute HIV infection) occurs 2-6 weeks after exposure. At this stage some patient develop acute symptoms for a short period of time (fever, malaise, headache, skin rash, lymphadenopathy, diarrhea, mouth ulcers and rarely encephalitis)

3. A long period of asymptomatic phase in which the patient may develop no symptoms for many years (up to 10 years) and looks normal.

4. Some HIV positive develop persistent generalized lymphadenopathy (PGL): lymph nodes more than 1 cm in diameter in two sites for more than 3 months.


5. Acquired immunodeficiency syndrome (AIDS): (CDC Classification category C disease) is defined by the development of specified opportunistic infections, unusual tumours, etc. when CD4 lymphocytes dropped to < 200 cells/ uL. The median interval from infection to the development of AIDS symptoms is around 7-10 years, although subgroups of patients exhibit 'fast' or 'slow' rates of progressionTypical symptoms of AIDS A. general symptoms and signs (fever, fatigue, weight loss, diarrhea, oral candida, perianal herpes, splenomegaly, etc. B. Specific (HIV associated conditions):

Specific HIV associated conditions

Disseminated cytomegalovirus infection Chronic mucocutanous, disseminated herpes simplex infection. Progressivemultifocalleukcoencephalopath Extra-pulmonary tuberculosis. Pneumocystis carinii pneumonia. Disseminated mycobacterium avium intracellulare. Candiasis of esophagus, bronchi or pulmpnary tree.


Extra-intestinal strongyloidiasisDisseminated histoplasmosisSecondary neoplasms: kaposi’s sarcoma, brain lymphoma, non-Hodgkin lymphoma. Other diseases.Notice: Every system or organ of the body may be involved like skin, GIT, liver, nervous system Icentral and peripheral), heart, respiratory system and others, Can be a differential diagnosis of many diseases.

immunodeficiency virus infection and the human acquired immunodeficiency syndrome

E.G.L. WILKINS
page 377

page 378
CLINICAL EXAMINATION IN HIV INFECTION
page 378

page 379


Antiretroviral therapy (ART)


In general, treatment should be commenced when the CD4 count falls below 250 cells/mm3 or the patient is symptomatic. A potent combination highly active antiretroviral therapy (HAART) should always be used. All patients should have a viral resistance test performed before commencing therapy as there is a 5-10% incidence of primary viral resistance.

The use of combination therapy (HAART), is now standard of care for HIV-infected patients requiring treatment. The introduction and widespread use of HAART has dramatically improved the prognosis for HIV-infected people.

However, a variety of problems may limit the effectiveness of HAART in controlling HIV infection. The initial difficulties may arise from a variety of causes, including: preexisting drug resistance, incomplete adherence, adverse effects and/or poor tolerability, drug-drug interactions, and pharmacogenomic determinants that affect tolerability or pharmacokinetics.

ANTIRETROVIRAL DRUGS

1. Nucleoside reverse transcriptase inhibitors (NRTIs). e. g. Lamivudine (3TC) Zidovudine (ZDV) Abacavir

2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) e. g. Nevirapine Efavirenz Delavirdine1 3. Protease inhibitors (PIs) e. g. Indinavir Ritonavir