10-24 ana de armas lecture guest

TB and HIV: a deadly human syndemic

intro

• TB and HIV are 2 most significant global health challenges
• TB is an infectious disease primarily affecting the lungs, caused by the bacterium mycobacterium TB
• HIV is a viral infection that weakens the immune system, making individuals more susceptible to various infections
• TB/HIV co-infection occurs when an individual is infected with both TB and HIV. this combo poses unique challenges and health risks
• vulnerable populations, such as those with limited access to healthcare or porr living conditions, are at a higher risk

TB and HIV syndeminc - 2 simultanous pandemics

africa

highest prevalence (800ppl/100 thousand ppl)

more

• HIV weakens immune system - allowing latent TB infections to necome active TB more easily
• active TB in HIV + individuals often progresses more rapidly, leading to more severe symptoms and complications
• diagnosing TB in HIV + patients can be challenging, as symptoms can be atypical or masked by other opportunistic infections
• conventional diagnostic tests may produce false negative results
• TB is a leading cause of death among HIV+ individuals
• synergistic effect of TB and HIV can significantly increase the risk of death if not diagnosed and treated promptly

Virus load somewhat controlled until progress to aids

= Where risk of TB infection is highest in HIV+ individuals

w/ initiation of ARV therapy – risk of TB infection still 5x higher than if you are HIV negative

If get TB and have HIV already – affects HIV replication, disease progression, etc.

Important – diagnosing TB in HIV patients can be challenging

Conventional tests – may produce false negative results

lifeitme TB risk in immunocompetent persons is 5-10% but in HIV+ individuals the annual TB risk is 5-15%

If latent infection untreated

- exposure to TB (health care, lab worker, etc, congregate living – higher risk) – highest risk is contact with HIV case

If healthy – likely wont progress to active TB, most likely latent

Immune suppression from HIV infection – very high risk if have TB

detection of immunological memory

use skin tests to detect immunological memory

TST (abt 2-3 days)

• TB skin test
• intradermal inoculation of PPD into volar aspect of forearm
• wait 48-72 hrs
• measure + record diameter of induration

IGRA (abt 2 days)

• quantiferon-TB gold plus IGRA
• take blood -> stimulates / cultures w/ TB antigens – see if t cell response

these tests are NOT rapid

cont.

If test + for immunological memory (the ones on right of last slide) – may have eliminated infection or have latent TB infection

- inability to differentiate btw the 2 possibilities if immunological memory is positive

Chest x ray is needed to fully diagnose

prevention and control

• Routine HIV testing is crucial; Early diagnosis and initiation of antiretroviral therapy (ART) can slow the progression of HIV and reduce the risk of TB.
• Regular screening for TB, including chest X-rays and sputum tests, should be part of the care for HIV-positive individuals.
• Early detection of TB and isoniazid preventive therapy (IPT) can prevent active TB.
• Improved ventilation and the use of personal protective equipment in healthcare facilities can reduce the transmission of TB among patients and healthcare workers
• HIV-positive individuals diagnosed with TB should receive integrated care that addresses both conditions.
• The management of TB in HIV-positive individuals often requires specific drug regimens and close monitoring for drug interactions and side effects.
• Community education and awareness are essential to combat stigma.

Preventative therapy – prevent transmission

Last point at bottom – many ppl don’t wanna be seen going to clinic for HIV or TB – bc of stigma

animal models for studying TB

Models for studying TB

- mouse, nonhuman primate

Human studies – try to identify correlates of latent TB infections

- certains cytokines/markers in blood/B and T cells populations, etc. describes

cellular targets of HIV and MTB

Cells targeted by pathogens

- HIV can infect dentritic cells, t cells, macrophages

Mycobacterium also infects macrophages

The 3 cell types talk to each other – coordinate immune response

- natural function of the 3 cells disrupted by TB (less able to respond, reduced anti HIV and TB response) = overwhelming inflammation constantly

HIV associated immune activation

Immune activation important

- SIV – pathogen affects nonhuman primates – particularly the mangabey

- don’t develop AIDS

- discovered they have very ___ (good?) immune activation

- BUT the rhesus monkey DOES develops AIDS and death

- but these show massive immune activation (more activation past certain amount = bad)

Immune activation is key to trajectory of infection

->Research tries to control immune activation if cannot control virus

->End organ diseases – things that can kill u if ur immune system weak from HIV/AIDS

TB-IRIS

immune reconstitution inflammatory syndrome (IRIS) - describes a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes following the initiation of highly active antirevtroviral therapy (HAART) in HIV infected individuals

preexisting infections may have previously been diagnosed and treated of they may be subclinical and later unmasked by host's regained capacity to mount inflammatory response

How ppl treated for coinfections

- if HIV- individual, a person w/ TB will be returned to latent if have therapy

TB vaccine: BCG

• bacille-calmette guerin (BCG) is the only approved vaccine for the prevention of TB
• live attenuated vaccine developed from mycobacterium bovis
• administered intradermally
• BCG is given neonatally in high TB burden countries
• ppl who were vaccinated with BCG may also test positive in TST but not IGRA
• BCG has limited efficacy
• no vaccine for hiv

Given 1-2 days after birth in countries w/ high amounts of TB

Could also be positive in TST but not IGRA if vaccinated w/ BCG

BCG efficacy

• infant BCG vaccination is beneficial, but not sufficient
• these results suggest that protective immunity against M tuberculosis should be boosted after childhood

provided reduced risk for TB diagnosis for up to 5 years - after was no reduced risk for acquisition

vaccine development

vaccines being developed

BCG - but intravenously instead of intradermally

subunit vaccines - pieces of proteins from bacteria + use those

BCG administration route

9/10 animals

high vs low dose vaccine

aerosol and diff routes used - wanna get in lungs where the TB can be bad

see results