Introduction to Microbiology

1. Introduction to Microbiology Anas Abu-Humaidan M.D. Ph.D. Lecture 31

2. Human immunodeficiency virus (HIV) • HIV is a retrovirus, and a lentivirus. • Retroviruses are a family ofEnveloped (+) RNA viruses that encode reverse transcriptase enzyme, which converts retroviral RNA genome into double-stranded DNA. • Lentivirus is a genus of the retrovirus family, they cause a long clinical latency period in infected patients in the presence of viremia before causing disease • HIV-1 surface glycoprotein gp120 attaches to CD4 cell and chemokine coreceptors, CCR5 or CXCR4

3. HIV reverse transcriptase is Highly error-prone, and mutants are regularly generated during infection This might explain the failure of the immune system to control the infection, the increases in viral virulence that appear to occur during the course of the infection, and the difficulty of developing an effective vaccine

4. Human immunodeficiency virus (HIV) • HIV is transmitted between humans in three ways: Sexually, vertically, and by exposure to contaminated blood or blood-derived products. • The virus has been demonstrated in particularly high titers in semen and cervical secretions. The probability of HIV transmission per unprotected sexual act is estimated at 0.0003 to 0.0015. • Mother to- child transmission can occur prepartum (via transplacental route 30% risk), intrapartum (through birth canal), and postpartum (through breast milk). • Transmission of infection to healthcare workers through accidental needlesticks that are potentially contaminated is very rare (considerably <1%). Intravenous drug abusers are at extremely high risk • Transmission does not occur through day-to-day nonsexual contact with infected individuals because of the fragility of the virus and the need for direct mucosal or blood contact.

5. Human immunodeficiency virus (HIV) • HIV infection is typically characterized by: • Transmission of HIV (common route: sexual transmission); • (2) an acute phase of intense viral replication and dissemination to lymphoid tissues (antiretroviral syndrome; flu- or mononucleosis-like illness in infected individuals); • (3) activation of innate and adaptive immune response but unable to • contain the highly replicating and mutating virus; • (4) A chronic (persistent) asymptomatic phase (clinical latency) of continued viral replication and immune activation • (5) An advanced phase of marked depletion of CD4 T lymphocytes (immune deficiency) leading to development of AIDS (opportunistic infections).

6. Acquired immune deficiency syndrome • Centers for Disease Control and Prevention (CDC) definition of AIDS stated: • All patients who are HIV antibody positive and have CD4+ T-lymphocyte counts lower • than 200/mm3 or less than 14% of total T lymphocytes have the disease. • Progression to AIDS is highly variable among individuals. • Patients with full-blown, untreated AIDS experience a wide spectrum of infections depending • on the severity of their immune deficiency. Pneumocystosis, candidiasis, mycobacteriosis, and CMV are common. • The diagnosis of HIV infection is most commonly confirmed by demonstrating antibody • to the virus or its components.

7. Acquired immune deficiency syndrome • Treatment involves six classes of antiretroviral agents These inhibitors are used in a combination therapy known as Anti Retroviral Therapy (ART). • Because current therapy is unlikely to eradicate HIV-1 infection, most patients are likely to stay on therapy for life. • Drug resistance is an expected development with treatment • Prophylaxis of opportunistic infections is especially important

8. Human immunodeficiency virus (HIV) • 35 million people living with HIV/AIDS worldwide • New infection declined by 33% in 2012 than 2001 worldwide • AIDS-related deaths decreased by 30% from 2005 to 2012 worldwide. • Since the late 1990s, the increases in early diagnosis, combined with more aggressive, highly active ART (HAART) in the United States, has greatly reduced opportunistic infections and delayed progression to death • Education is the cornerstone of prevention. Condoms prevent transmission. • Much research is underway to develop vaccines against the virus, but the marked mutability of HIV greatly complicates this approach

9. Papillomaviruses • Naked capsid, double-stranded, circular DNA viruses. • Papillomaviruses cause epidermal papillomas and warts (الثآليل).

10. Genital warts

11. Skin warts • Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. • They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful • Warts are very common, the estimated current rate of non-genital warts among the general population is 1–13%.

12. Genital warts • Genital warts are a common cause of morbidity, with estimates of up to 50% of the population HPV at some point in their lifetime • 90% of cases are related to HPV subtypes 6 and 11. • HPV Subtypes 16 and 18 are associated with squamous cell carcinoma. • Women tend to be affected more than men in most settings.

13. Genital warts • On average, physical symptoms begin approximately 2 to 3 months after initial contact, Many studies estimate the rate of subclinical HPV infection to be as high as 40% • Approximately 30 percent of all warts will regress within the first four months of infection. • Significant risk factors for long-term wart persistence include host immunosuppression, infection with high-risk HPV subtypes, and an older patient age • Lesions are rarely considered to be painful; however, they are often associated with severe discomfort, burning, and pruritis

14. Genital warts • A vaccine known as Gardasil protects against four strains of HPV that cause cancer, and is used to prevent genital warts • These vaccines are most effective if given to children before they become sexually active • Pap tests, can help detect vaginal and cervical changes caused by genital warts or the early signs of cervical cancer

15. Genital warts • Current treatment of HPV is usually either cytotoxic or surgical. • Recurrences are common after cessation of treatment because of survival of virus or viral DNA in the basal layers of the epithelium. Warts can be removed by laser or freezing with liquid nitrogen. Imiquimod acts as an immune response modifier, cells treated secrete cytokines like interferons important in defence against viruses

16. Further reading: • Sherris Medical Microbiology, sixth edition • Chapter 18-19