Pathology - Block 3 Hiv

Front 1

HIV screening guidelines

Back 1

- Screen any patient aged 13-64yrs (any healthcare setting). Any pregnant ptn (initial visit), Annually if -- IVDU, commercial sex worker, more than 1 sexual partner since last HIV test

Front 2

Importance of testing

Back 2

- Dx allows individuals to get anti-retroviral tx = decr mortality. (40% of new HIV caes also diagnosed with AIDS with 1 yr). Tx decr transmission to others. Many missed opportunities (Most HIV+ ptns had many previous visits)

Front 3

Differential dx

Back 3

Viral URI, Mononucleosis, Group A strep, Gonorrhea, chlamydia

Front 4

Acute Retroviral syndrome

Back 4

2-6 wks after infxn. primary response to infxn. Sx -- (seen in 80%) fever (80%), arthralgia/myalgia (54%), anorexia/weight loss (54%), Rash (51%), lymphadenopathy, fatigue/malaise (68%), pharyngitis/oral ulcers (44%). 1% of individuals tested for infectious mononucleosis were positive for acute HIV infxn. High levels of viremia -- widespread seeding of other lymph tissue, 8-22 times more infectious to others than in chronic HIV phase. Decreased CD4 cells in circulation. HIV-specific CD8 T cell response contains infxn.

Front 5

Tests for HIV

Back 5

1. AB test -- negative until 4-6 wks after infxn. ELISA screening test (cheap, accessable, fast) - laboratory based, rapid testing (20 min), blood, oral fluid. Western Block confirmatory test.; 2. Antigen test -- detect infxn after 10-14 days, expensive, HIV viral load/RNA, p24 antigen; 3. Combination of HIV AB/antigen test -- can detect infxn up to 9 days earlier than AB test, but later than HIV RNA test; 4. Pooled HIV RNA testing -- samples 20-90 ptn combined. positive pools --> test run on progressively smaller pools. increases yield of HIV testing by up to 10% compared to AB testing alone.

Front 6

HIV tx concepts

Back 6

Resistance testing prior to tx. Goals of tx -- undetectable viral load (<50 copies/microL), increase in CD4 T cells, eliminate HIV-related sx. follow T-cell counts every 3 months. Current consensus -- start tx if CD4 count is <500cells/mm3, Tx interruption not recommended.

Front 7

Antiviral Tx

Back 7

3 medications. 2 classes of drugs: Nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), Protease inhibitor (PI), integrase inhibitor, Fusion inhibitor, CCR5 receptor antagonist.

Front 8

Perinatal transmission of HIV

Back 8

Untreated - 25% infected. One drug (AZT) - 8% (orally to mother, IV during labor, Orally to infant). Standard of care - 0-1% (HAART to mother - 2nd trimester, IV AZT during labor, AZT to baby x 6 wks, formula feeding in developed nations)

Front 9

Factors associated with HIV transmission in healthcare exposure

Back 9

deep injury, visible blood on device, intravascular device. terminally ill source ptn. Efficacy of post-exposure Prophylaxis (PEP) case control study - Seroconverters -- 0.2 times as likely to have taken PEP compared to non-seroconverters.

Front 10

Definition of exposure to HIV - materials NOT considered infectious for HIV unless visibly bloody

Back 10

1. Percutaneous injury (needlestick, cut) OR contact of mucous membrane or non-intact skin & 2. Blood, tissue, other body fluid that are potentially infectious (cerebrospinal, synovial, pleural, pericardial, peritoneal, or amniotic fluids; semen or vaginal secretions) / Not infectious -- feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus

Front 11

Rule of 3s for needle stick exposures

Back 11

Hepatitis B 30%, Hepatitis C 3%, HIV 0.3%

Front 12

Postexposure prophylaxis (PEP)

Back 12

current standard -- 2 or 3 drug regimen based on exposure type & source ptn. report to occupational health immediately.

Front 13

Nonoccupational PEP

Back 13

nPEP should be considered for high-risk exposures. Animal models support efficacy -- decreasing efficacy over time after exposure (Best is ASAP, not indicated after 72 hrs). Best outcomes with 28 days of ARVs

Front 14

UCSF nPEP study

Back 14

conclusion -- most subjects did not demonstrate behavioral disinhibition following nPEP. nPEP should be routinely considered for high-risk exposures. / barriers -- low awareness, mechanism for pmt (disparate distribution), knowledge/willingness of first-line prescribers.

Front 15

Topical Microbicides

Back 15

concept -- application of anti-HIV gel intravaginally/anally. apply regularly/prior to anticipated sex/after sex. Chemical agents or antiviral agents. 11 negative trials of 6 products. "Tenofovir gel" (NRTI). 40% reduction in HIV transmission among all women in study, but 54% reduction in women that adhered highly to the protocol.

Front 16

Pre-exposure prophylaxis

Back 16

Concept -- intermittent, scheduled, or episodic ARV use may prevent HIV transmission

Front 17

iPrEx study

Back 17

Daily tenofovir-emtricitabine OR placebo. followed for 1.2 yrs. --> Fewer seroconversion in TDF-FTC arm (Relative risk reduction of 44% - intention to tx), Drug-level comparison (compared efficacy - relative risk reduction of 92%) --> Antiretroviral chemoprophylaxis is efficacious. cost effectiveness is determined by risk of individual, cost of medication, incidence of HIV in population. Behavioral research and interventions must accompany biomedical interventions.

Front 18

Amniotic fluid is important for?, produced in?

Back 18

Importance -- cushioning the developing fetus, allowing freedom of movement, stimulating lung growth and devo. ; production -- before 12 wks - secretions from multiple non-renal sources + a small amt of fetal urine; after 12 wks - almost entirely by the fetal kidneys.

Front 19

Oligohydramnios, Polyhydramnios, Anhydramnios

Back 19

Oligohydramnios - decr amniotic fluid volume, Polyhydramnios - incr amniotic fluid volume, Anhydramnios - no amniotic fluid

Front 20

Oligohydramnios -- result of? outcome depends on?

Back 20

could be result of multiple problems -- Amniotic fluid leakage (ruptured membranes), inadequate amniotic fluid production - kidney disorders (bilateral renal agenesis, renal dysplasia, polycystic kidney dz), Urethral atresia/obstruction; Pulmonary hypoplasia, Potter sequence -- Abnormal facies (inner canthal folds, flattened nasal bridge, beaked nose, micrognathia -small recessed jaw, low-set, flat, floppy ears), Clubfeet, large spade-like hands and feet, bowed legs, Pterygia (skin webs across joints resulting from decreased movement). / outcome - dependent on the severity and chronicity of the oligohydramnios, and ultimately depends on the degree of pulmonary hypoplasia

Front 21

Pterygia

Back 21

Pterygia (skin webs across joints resulting from decreased movement).

Front 22

Autosomal recessive polycystic kidney dz

Back 22

Rare, AR inheritance (parents are usually asymptomatic carriers), Mutations in the PKHD1 gene encoding fibrocystin lead to renal cysts and hepatic fibrosis (exact mechanism unknown), variable penetrance. usually lethal. Supporative case includes hemodialysis, oxygen, and mechanical ventilation. Rarely, renal transplantation in early infancy may extend life -- again, complications occur from pulmonary hypoplasia and hepatic fibrosis.

Front 23

Necrotizing Enterocolitis

Back 23

Premature and low birthweight infants are at highest risk. occurs shortly after starting feeds. Clinical -- Abdominal distention and tenderness, Diarrhea (often bloody), Ileus (intestinal obstruction), Sepsis. Pathogenesis -- unknown. likely results from combination of gut immune sys not fully developed (esp. in preemies), oral feeds introduce bacteria to neonatal gut (sterile in utero), food and bacteria elicit immune response (cytokines), mucosal injury, inadequate intestinal blood flow. Medical mgmt -- stop feeds and rest gut, give IV fluids, electrolytes, and broad-spectrum antibiotics, supportive case. Surgical mgmt -- resect affected segment, can cause malabsorption & short gut syndrome.

Front 24

Hirschsprung dz

Back 24

Partial to total colonic aganglionosis (absence of ganglion cells in both the submucosal and myenteric plexus, involving the rectum and a variable amount of more proximal colon). caused by failure of neural crest cells to migrate the full length of bowel during devo. 1:5000 births, M>F. some hereditary predisposition. more frequent in Down syndrome. Clinical -- varies with length of affected segment. failure to pass muconium within first 48 hrs of life, constipation, abdominal distention. Medical mgmt -- prompt dx to prevent complications, fluid/electrolyte maintenance, possible antibiotic therapy to prevent peritonitis/infxn. Surgical mgmt -- rectal suction biopsy of mucosa used for initial dx, curative procedure involved resection of affected segment.