Tuberculosis in relation to HIV

Last updated

The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. [1] Tuberculosis is the most common contagious infection in HIV-Immunocompromised patients leading to death. [2] These diseases act in combination as HIV drives a decline in immunity while tuberculosis progresses due to defective immune status. This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality (see Multi-drug-resistant tuberculosis). Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. A study on gold miners of South Africa revealed that the risk of TB was doubled during the first year after HIV seroconversion. [3] Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection. [4] The risk of TB generally remains high in HIV-infected patients, remaining above the background risk of the general population even with effective immune reconstitution and high CD4 cell counts with antiretroviral therapy. [5]

Contents

Tuberculosis and HIV infection

Mycobacterium tuberculosis is the most common cause of Tuberculosis disease (TB). Airborne transmission typically causes TB infection in both immunocompetent and immunocompromised hosts.[ citation needed ]

Tuberculosis, is categorized into two types of infection: latent infection or active TB disease.[ citation needed ]

After penetration into the respiratory tract, the Mycobacterium bacilli infect macrophages. T-lymphocytes start producing many cytokines (interferon gamma, interleukin-2, tumour necrosis factor alpha, and macrophage colony-stimulating factor) to activate macrophages and cytotoxic cells to inhibit their intracellular growth.[ citation needed ]

In those infected, there is a 5–10% chance that latent TB infection will progress into active tuberculosis disease. If proper treatment is not given in case of active disease, then death rate is about 50%. [6]

HIV infection is a lifelong illness with three stages of disease. Medicine to treat HIV can slow or prevent progression from one stage to the next. Treatment can also reduce the chance of transmitting HIV to someone else.[ citation needed ]

Pathogenesis of co-infection of HIV and tuberculosis

HIV/TB infection is a bi-directional interaction of the two pathogens.[ citation needed ]

TB disease appears when the immune response is unable to stop the growth of mycobacteria. The cytokine IFN-γ plays a pivotal role in signaling of the immune system during infection. Reduced production of IFN-γ or its cellular receptors lead to severe and fatal TB. During HIV infection, IFN-γ production is decreased dramatically which leads to an increased risk of developing reactivation or reinfection by M. tuberculosis in these HIV/TB patients. [8]

TB also influences HIV evolution. Proinflammatory cytokine production by tuberculous granulomas (in particular TNFα) has been associated with increased HIV viraemia, which might accelerate the course of disease. [9] The risk of death in HIV/TB infected patients is twice that of HIV-infected patients without TB, with most deaths caused by progressive HIV infection, rather than TB. [10]

Prevention

When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. [11] A Cochrane review [12] investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.[ citation needed ]

Treatment

It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. [13] Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. [14] The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART. [15]

A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. [16] The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.[ citation needed ]

Research at molecular level

A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. [17] Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). [18] It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology. [19]

Related Research Articles

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

The spread of HIV/AIDS has affected millions of people worldwide; AIDS is considered a pandemic. The World Health Organization (WHO) estimated that in 2016 there were 36.7 million people worldwide living with HIV/AIDS, with 1.8 million new HIV infections per year and 1 million deaths due to AIDS. Misconceptions about HIV and AIDS arise from several different sources, from simple ignorance and misunderstandings about scientific knowledge regarding HIV infections and the cause of AIDS to misinformation propagated by individuals and groups with ideological stances that deny a causative relationship between HIV infection and the development of AIDS. Below is a list and explanations of some common misconceptions and their rebuttals.

<span class="mw-page-title-main">Cryptococcosis</span> Potentially fatal fungal disease

Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and brain, where it appears as a meningitis. Cough, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity and confusion or changes in behavior. It can also affect other parts of the body including skin, where it may appear as several fluid-filled nodules with dead tissue.

<span class="mw-page-title-main">Tuberculosis management</span>

Tuberculosis management describes the techniques and procedures utilized for treating tuberculosis (TB) or simply a treatment plan for TB.

HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.

Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in some cases of HIV/AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

<i>Mycobacterium avium-intracellulare</i> infection Medical condition

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex (MAC), which is made of two Mycobacterium species, M. avium and M. intracellulare. This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS, it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) is when a person is infected with Mycobacterium tuberculosis, but does not have active tuberculosis (TB). Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these people will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.

<span class="mw-page-title-main">HIV/AIDS</span> Spectrum of conditions caused by HIV infection

HIV(human immunodeficiency virus) is a retrovirus that attacks the immune system. It can be managed with treatment. Without treatment it can lead to a spectrum of conditions including AIDS (acquired immunodeficiency syndrome).

<span class="mw-page-title-main">Extensively drug-resistant tuberculosis</span> Tuberculosis that is resistant to the most effective drugs

Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-TB).

CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region, similarly known as immunoglobulin. It belongs to the antibody (Ig) gene family. CD4 is a surface receptor for human immunodeficiency virus (HIV). The CD4 immunoadhesin molecular fusion allow the protein to possess key functions from each independent subunit. The CD4 specific properties include the gp120-binding and HIV-blocking capabilities. Properties specific to immunoglobulin are the long plasma half-life and Fc receptor binding. The properties of the protein means that it has potential to be used in AIDS therapy as of 2017. Specifically, CD4 immunoadhesin plays a role in antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells. While natural anti-gp120 antibodies exhibit a response towards uninfected CD4-expressing cells that have a soluble gp120 bound to the CD4 on the cell surface, CD4 immunoadhesin, however, will not exhibit a response. One of the most relevant of these possibilities is its ability to cross the placenta.

T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been termed as Treg17 cells.

Diffuse infiltrative lymphocytosis syndrome (DILS) is a rare multi-system complication of HIV believed to occur secondary to an abnormal persistence of the initial CD8+ T cell expansion that regularly occurs in an HIV infection. This persistent CD8+ T cell expansion occurs in the setting of a low CD4+/CD8+ T cell ratio and ultimately invades and destroys tissues and organs resulting in the various complications of DILS. DILS classically presents with bilateral salivary gland enlargement (parotitis), cervical lymphadenopathy, and sicca symptoms such as xerophthalmia and xerostomia, but it may also involve the lungs, nervous system, kidneys, liver, digestive tract, and muscles. Once suspected, current diagnostic workups include (1) confirming HIV infection, (2) confirming six or greater months of characteristic signs and symptoms, (3) confirming organ infiltration by CD8+ T cells, and (4) exclusion of other autoimmune conditions. Once the diagnosis of DILS is confirmed, management includes highly active antiretroviral therapy (HAART) and as-needed steroids. With proper treatment, the overall prognosis of DILS is favorable.

<span class="mw-page-title-main">HIV disease–related drug reaction</span>

HIV disease–related drug reaction is an adverse drug reaction caused by drugs used for the treatment of HIV/AIDS.

<span class="mw-page-title-main">Signs and symptoms of HIV/AIDS</span>

The stages of HIV infection are acute infection, latency, and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, swollen lymph nodes, inflammation of the throat, rash, muscle pain, malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts, various opportunistic infections, cancers, and other conditions.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Harriet Mayanja-Kizza, MBChB, MMed, MSc, FACP, is a Ugandan physician, researcher, and academic administrator. She is the former Dean of Makerere University School of Medicine, the oldest medical school in East Africa, established in 1924.

<span class="mw-page-title-main">Sharon Lewin</span> Australian infectious disease physician and researcher

Sharon Ruth Lewin, FRACP, FAHMS is an Australian physician who is the inaugural Director of The Peter Doherty Institute for Infection and Immunity. She is also a Professor of Medicine at The University of Melbourne, a National Health and Medical Research Council (NHMRC) Practitioner Fellow, Director of the Cumming Global Centre for Pandemic Therapeutics, and President of the International AIDS Society (IAS).

<span class="mw-page-title-main">Henry Mwandumba</span> African professor of medicine

Henry Charles Mwandumba is an African Professor of Medicine and the Director of the Malawi-Liverpool-Wellcome Programme. He works on the tuberculosis phagosome in the University of Malawi College of Medicine, and serves as President of the Federation of African Immunological Societies. In 2019 Mwandumba was awarded the Royal Society Africa Prize.

Andrew Ddungu Kambugu is a Ugandan physician who serves as The Sande-McKinnell Executive Director at Uganda Infectious Disease Institute and a Honorary Senior lecturer at Makerere University College of Sciences. He is also an Adjunct Associate Professor at the University of Minnesota. In July 2020, he was appointed to the United Nations 2021 Food System Scientific Group.

References

  1. ↑ World Health Organization (2012). Global Tuberculosis Report 2012 (PDF). ISBN   978-92-4-156450-2.
  2. ↑ World Health Organization (1999). "Tuberculosis infection control in the era of expanding HIV care and treatment" (PDF).{{cite journal}}: Cite journal requires |journal= (help)
  3. ↑ "Tuberculosis and HIV". January 2013. Archived from the original on 2018-07-29. Retrieved 2013-05-06.{{cite journal}}: Cite journal requires |journal= (help)
  4. ↑ Tuberculosis (TB) Archived 2018-07-23 at the Wayback Machine . AIDS InfoNet. February 4, 2014.
  5. ↑ Worodria, W.; Massinga-Loembe, M.; Mazakpwe, D.; Luzinda, K.; Menten, J.; Van Leth, F.; Mayanja-Kizza, H.; Kestens, L.; Mugerwa, R. D.; Reiss, P.; Colebunders, R.; TB-IRIS Study Group (2011). "Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy" . Journal of Acquired Immune Deficiency Syndromes. 58 (1): 32–37. doi: 10.1097/QAI.0b013e3182255dc2 . PMID   21654499. S2CID   45100392. Archived from the original on June 24, 2012.
  6. ↑ L, Aaron; D, Saadoun; I, Calatroni; O, Launay; N, Mémain; V, Vincent; G, Marchal; B, Dupont; O, Bouchaud; D, Valeyre; O, Lortholary (May 2004). "Tuberculosis in HIV-infected patients: a comprehensive review". Clinical Microbiology and Infection. 10 (5): 388–398. doi: 10.1111/j.1469-0691.2004.00758.x . PMID   15113314.
  7. ↑ U.S. Department of Health & Human Services. "STAGES OF HIV INFECTION". AIDS.gov. Retrieved 7 December 2015.
  8. ↑ Ottenhoff, Tom H.M; Kumararatne, Dinakantha; Casanova, Jean-Laurent (November 1998). "Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria". Immunology Today. 19 (11): 491–494. doi:10.1016/S0167-5699(98)01321-8. PMID   9818540.
  9. ↑ Garrait, V; Cadranel, J; Esvant, H; Herry, I; Morinet, P; Mayaud, C; IsraelBiet, D (September 1997). "Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV". Journal of Immunology. 159 (6): 2824–2830. doi: 10.4049/jimmunol.159.6.2824 . PMID   9300705. S2CID   28911458 . Retrieved 7 December 2015.
  10. ↑ WHALEN, C; HORSBURGH, CR; HOM, D; LAHART, C; SIMBERKOFF, M; ELLNER, J (January 1995). "Accelerated course of human immunodeficiency virus infection after tuberculosis". American Journal of Respiratory and Critical Care Medicine. 151 (1): 129–135. doi:10.1164/ajrccm.151.1.7812542. PMID   7812542 . Retrieved 7 December 2015.
  11. ↑ Smieja, M. J.; Marchettu, C. A.; Cook, D. J.; Smaill, F. M. (1999). "Isoniazid for preventing tuberculosis in non-HIV infected persons". Cochrane Database of Systematic Reviews. 1999 (2): CD001363. doi:10.1002/14651858.CD001363. PMC   6532737 . PMID   10796642.
  12. ↑ Zunza, M.; Gray, D. M.; Young, T.; Cotton, M.; Zar, H. J. (2017). "Isoniazid for preventing tuberculosis in HIV-infected children". Cochrane Database of Systematic Reviews. 2017 (8): CD006418. doi:10.1002/14651858.CD006418.pub3. PMC   5618450 . PMID   28850172.
  13. ↑ Clinical trial number NCT00933790 for "Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis" at ClinicalTrials.gov
  14. ↑ Lawn, Stephen D; Harries, Anthony D; Anglaret, Xavier; Myer, Landon; Wood, Robin (October 2008). "Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa" (PDF). AIDS. 22 (15): 1897–1908. doi:10.1097/qad.0b013e32830007cd. ISSN   0269-9370. PMC   3816249 . PMID   18784453.
  15. ↑ Kapoor, Gauri; Singh, Neha (2018). "Role of apoptotic markers in paediatric acute lymphoblastic leukaemia". Indian Journal of Medical Research. 147 (3): 225–227. doi: 10.4103/ijmr.ijmr_906_17 . ISSN   0971-5916. PMC   6022391 . PMID   29923509.
  16. ↑ Uthman, Olalekan A.; Okwundu, Charles; Gbenga, Kayode; Volmink, Jimmy; Dowdy, David; Zumla, Alimuddin; Nachega, Jean B. (7 July 2015). "Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis". Annals of Internal Medicine. 163 (1): 32–9. doi:10.7326/M14-2979. PMID   26148280. S2CID   207538325.
  17. ↑ Ramaseri Sunder, S.; Hanumanth, S. R.; Nagaraju, R. T.; Venkata, S. K.; Suryadevara, N. C.; Pydi, S. S.; Gaddam, S.; Jonnalagada, S.; Valluri, V. L. (2012). "IL-10 high producing genotype predisposes HIV infected individuals to TB infection". Human Immunology. 73 (6): 605–611. doi:10.1016/j.humimm.2012.03.012. PMID   22507621.
  18. ↑ Tadokera, Rebecca; Wilkinson, Katalin A.; Meintjes, Graeme A.; Skolimowska, Keira H.; Matthews, Kerryn; Seldon, Ronnett; Rangaka, Molebogeng X.; Maartens, Gary; Wilkinson, Robert J. (April 2013). "Role of the Interleukin 10 Family of Cytokines in Patients With Immune Reconstitution Inflammatory Syndrome Associated With HIV Infection and Tuberculosis". The Journal of Infectious Diseases. 207 (7): 1148–1156. doi:10.1093/infdis/jit002. ISSN   0022-1899. PMC   3583273 . PMID   23303806.
  19. ↑ Walker, N. F.; Clark, S. O.; Oni, T.; Andreu, N.; Tezera, L.; Singh, S.; Saraiva, L. S.; Pedersen, B.; Kelly, D. L.; Tree, J. A.; d'Armiento, J. M.; Meintjes, G.; Mauri, F. A.; Williams, A.; Wilkinson, R. J.; Friedland, J. S.; Elkington, P. T. (2012). "Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases". American Journal of Respiratory and Critical Care Medicine. 185 (9): 989–997. doi:10.1164/rccm.201110-1769OC. PMC   3359940 . PMID   22345579.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.