3.1 blood borne pathogens

What are the three blood borne viruses?

• HIV (human immunodeficiency virus)

• HBV (hep b virus)

• HCV (hep c virus)

How many people have died of global HIV as of 2023?

~42.3 million people but 6 have been cured (stem-cell transplantation)

A +RNA, enveloped, retrovirus (viral retrotranscriptase RNA → DNA ) that infects CD4+; also macrophages, dendritic cells

HIV

What are the important HIV proteins?

• Gp160 (Env)

• Proteases

• Reverse transcriptase (RT)

• Integrate

These are all antiviral targets!

This envelope protein of virus binds CD4 receptor and CXCR4 and CCR5 co-receptors of the host cell to fuse the viral envelope w the cell membrane

Mechanism of gp160 (Env)

Mechanism of protease

Cleaves viral poly proteins into functional proteins

Generates DNA from viral RNA template

Reverse transcriptase (RT)

Integrates viral DNA into the the host genome

Integrate

• Transmitted in blood, genital secretions, breast milk

  • Needle stick accidents, open wound or mucous membranes

HIV encounter

• Enters body through blood or mucosa

• Infects dendritic cells, then CD4+ lymphocytes

• Progeny virus is shed into the bloodstream (viremia)

• Spread to brain, spleen, GI

HIV entry and spread

Acute a stage includes “mononucleosis-like” symptoms that can last 1-4 weeks, incubation is 2-6 weeks

HIV

• 4th generation immunoassays: combine (blank) antigen and (blank) antibodies

• Earliest positive 15-20 days

• Test for viral RNA if symptomatic and <15 days of exposure

  • First to peak after infection is viral RNA → p24 antigen → antibody

HIV testing

What is the HIV window?

Time between getting HIV and when it will show on tests:

• Nucleic acid test: 10-33 days

• Antigen/antibody lab test: 18-45

• Rapid antigen/antibody test: 18-90 days

• Antibody test: 23-90 days

This latency stage is:

• Asymptomatic

• Viral load is at a low level

• Continuous viral repli leads to CD4 destruction

HIV: low levels of HIV RNA and declining CD4 counts

• CD4 cell count <200 so cell mediated immunity is lost

• Weight loss, wasting

• Opportunistic infections: bacteria, viruses, fungi, Protozoa (those usually non-pathogenic become pathogenic

• Tumors

• Neurological diseases

AIDS: high levels of RNA low CD4

HAART/ART

Highly active anti-retroviral therapy: cocktail of inhibitors that target different stages in repli (see HIV proteins: 4)

“Chronic manageable disease”: CD4 levels recover and viral plasma RNA undetectable but still lifetime of drugs

Occupational exposures:

• Per cutaneous injury (needle stick)

• Mucous membranes or non-intact skin

• Non-infectious unless visible blood: “external” body fluid

• More blood = more risk of infection

PEP vs PrEP

• PEP: post exposure prophylaxis (preventative)

  • ART regimen, short-term that decreases likelihood of HIV infection from exposure

  • Start asap w/in 72 hours of exposure for 28 days, rested 4-6wks, 12, 24; secondary transmission to others rare but modify behavior first 6-12 weeks after exposure

• PrEP: Pre Exposure Prophylaxis

liver disease mostly cased by viruses but could also be caused by toxins in alcohol or mushrooms

hepatitis

three hepatitis viruses that result in acute or chronic disease and transmission is blood and bodily fluids:

• Hep B: chronic is 5%

• Hep C: chronic is 80%

• Hep D, needs Hep B to be viral and repli

which hep virus is transmitted by fecal/oral route and causes acute disease?

Hep A and E

• efficient vaccine is available for this hepatitis virus

• major blood-borne pathogen

• liver disease and cancer

• around for a long time and ~257 million people worldwide aer chronically infected

HBV

HBV encounter, entry, and spread

• blood or genital; needle sticks also sharing razors or toothbrushes, vertical

• spreads to liver

• long incubation: 4-26 weeks

labs that show

• increased levels of aminotransferases

• absence of Abs to HAV, HBV. HCV

• HBsAg detected

acute HBV infection

what is HBsAg?

hep B surface antigens

• binds host receptors

• key serological marker of HBV infection

• elicits protective Abs

• subunit vax

increased levels of aminotransferases marker of

liver injury

HBsAg marker of

active infection

anti-HBs antibodies marker of

immunity

how many HBV diseases end in acute, asymptomatic infection?

~2/3

how many of the acute infections recover? turn into chronic infection? fulminant hepatitis?

• 95% (low chance of reinfection

• 5% (cirrhosis and hepatocellular carcinoma)

• <1% (massive hepatic necrosis and leads to cell death)

which hep virus is oncogenic?

HBV (cancer causing)

T or F: HBV is an enveloped, ds or ssDNA virus

true! with HBsAg and HBcAg

what is HBcAg?

hep B core antigen

• forms viral capsid

• elicits Abs

what is HBs window?

when HBsAg is gone but anti-HBs IgGs (protective Abs, diagnostic of lover disease not quite HBV infection) undetectable

• persistent viremia

• HBsAg stay high

• no anti-Hs IgGs (instead IgMs then IgGs)

• liver cells constantly damaged and regenerated

• elevated aminotransferases due to liver injury

• leads to cirrhosis, hepatocellular carcinomas; great regen capacity

chronic HBV infection 5% of cases

what Ag is present with acute HBV infection?

HBsAg

what seroconversion occurs with a resolved HBV infection?

HBsAg → anti-HBs IgG

what Ag is present with chronic HBV infection?

HBsAg for >6mo

the three serological for HBV diagnosis and their types of infection

which serological marker is present for vaccination HBV?

anti-HBs IgGs

• HBsAg: present

• Anti-HBs IgGs: no

• Anti-HBc: yes window IgM

acute HBV

• HBsAg: present

• Anti-HBs IgGs: no

• Anti-HBc: IgG

chronic HBV

• HBsAg: no

• Anti-HBs IgGs: present

• Anti-HBc: IgG

resolved HBV

• HBsAg: no

• Anti-HBs IgGs: present

• Anti-HBc: no

vaccination for HBV

treatment for acute vs chronic HBV?

acute: self-resolving

chronic: no cure but use antivirals like ribavirin to reduce viral load or PEGylated interferon (stabilized interferon)

HBV prevention: active vs passive immunization

active: subunit vax is recombinant HBsAg for infants and healthcare workers

passive: anti-HBV IgGs (HBIG) infants of chronic HBV carriers and take w subunit vax

when to take HBV PEP?

• exposure to HBV-infected blood, vaccine w/in 12 hours of exposure plus HBIG

*but if you have been vax and have documented anti-HBs IgG, you do not need PEP

enveloped, +RNA virus in family of hepacivirus, discovered 1989 (recently). in the US is the leading cause of liver transplant

HCV

HCV encounter, entry, spread

transmitted blood (some risk w razors and toothbrushes and low risk with sex)

spreads to liver, multiplies then to blood

long incubation: 4-26 weeks

of the ~2/3 acute asymptomatic HCV infections how many recover? how many become chronic?

• 20%

• 80%; cirrhosis 20-30% → hepatocellular carcinoma

  • high prevalence bc HCA is an error prone RNA virus that mutates easy with RdRp low fidelity frequent mistakes with no correction = vast genetic diversity

• HCV RNA (genome): yes

• aminotransferase levels: high

• anti-HCV Ab: no early yes later

acute HCV

• HCV RNA (genome): yes

• aminotransferase levels: variable

• anti-HCV Ab: yes

chronic HCV

• HCV RNA (genome): no

• aminotransferase levels: normal

• anti-HCV Ab: yes

resolved HCV

T or F: positive anti-HCV Ab test distinguishes resolved vs chronic infections

FALSE! need to test for HCV RNA

T or F: to distinguish from acute vs chronic infection you check for HCV RNA then check again in 3mo

true :)

how to treat chronic HCV?

antivirals, pegylated interferon (prolong immune response)

outcome of HCV treatment:

SVR (sustained virologic response): no HCV RNA 6mo after end of treatment (45-90% ppts cured?)

no vaccine or PEP

• vaccine: yes

• PEP: yes

• antiviral: yes

• survival on fomite: 1-3 weeks

• risk of infection after needle stick: 7-30% (viral load)

HBV

• vaccine: no

• PEP: no

• antiviral: yes

• survival on fomite: up to 4 days

• risk of infection after needle stick: 2%

HCV

• vaccine: no

• PEP: yes

• antiviral: yes

• survival on fomite: few hours

• risk of infection after needle stick: 0.3%

risk w bloody dental procedures

HBV: prevent w PPE, safe injection practices, HBV vax

risk w needle stick

HCV HIV