Chronic Disease PDF

Ministry of Higher Education and Scientific Research University of Wasit/College of Medicine Third Year Module: infection and immunity S5 Chronic disease Sheama Alali  Chronic infectious diseases are long-lasting infections caused by var...

Ministry of Higher Education and Scientific Research University of Wasit/College of Medicine Third Year Module: infection and immunity S5 Chronic disease Sheama Alali  Chronic infectious diseases are long-lasting infections caused by various pathogens, such as bacteria, viruses, fungi, or parasites, that persist in the body for months or even years. Unlike acute infections, which typically resolve after a short period, chronic infections can have ongoing or recurrent symptoms and may contribute to long-term health complications  Key Characteristics 1. Prolonged Duration: Symptoms and the presence of the pathogen last for an extended period, often beyond 6 months. 2. Persistence: The pathogen is not completely eradicated by the host’s immune system or treatment. 3. Subclinical or Latent Phases: The disease may have periods with minimal or no symptoms (latent phase) but can reactivate or worsen over time  Common Chronic Infectious Diseases 1. HIV/AIDS: Caused by the Human Immunodeficiency Virus (HIV), this disease weakens the immune system over time, leading to increased vulnerability to opportunistic infections. 2. Tuberculosis (TB): A bacterial infection caused by Mycobacterium tuberculosis, which primarily affects the lungs but can spread to other parts of the body. 3. Hepatitis B and C: Viral infections that primarily affect the liver, leading to chronic liver disease, cirrhosis, and liver cancer if untreated. 4. Lyme Disease: Caused by the Borrelia burgdorferi bacterium, transmitted through tick bites. It can lead to persistent symptoms even after initial treatment. 5. Chronic Fungal Infections: Infections like chronic pulmonary aspergillosis, which can persist in individuals with weakened immune systems or underlying lung conditions. 6. Leprosy (Hansen’s Disease): A bacterial infection caused by Mycobacterium leprae, affecting the skin, nerves, and mucous membranes.  HIV/AIDS Human immune deficiency virus (HIV) types, derived from primate lentviruses, are the etiologic agents of AIDS. The illness was first described in 1981, and HIV- 1 was isolated by the end of 1983. Since then, AIDS has become a worldwide epidemic, expanding in scope and magnitude as HIV infections have affected different populations and geographic regions. Millions are now infected worldwide; People living with HIV AIDS world map.  The structure of the HIV The structure of the HIV virus is complex and consists of several key components. Here’s a breakdown of its main parts: 1. Envelope (Outer Layer): Lipid Bilayer: The outermost layer of HIV is a lipid bilayer derived from the host cell’s membrane. This layer helps the virus merge with host cells to initiate infection. Glycoproteins (gp120 and gp41): Two major glycoproteins are embedded in the envelope: gp120: Facilitates attachment to the CD4 receptor on host cells. gp41: Assists in the fusion of the viral envelope with the host cell membrane, allowing the viral genome to enter the cell. 2. Capsid (Protein Shell): Located within the envelope, the capsid is a cone-shaped structure made up of a protein called p24. This shell protects the viral RNA and enzymes inside. 3. Viral Genome: HIV is a single-stranded RNA virus. It contains two identical strands of RNA as its genetic material. 4. Enzymes: HIV carries several essential enzymes for its life cycle: Reverse Transcriptase: Converts viral RNA into DNA once the virus enters a host cell. Integrase: Integrates the viral DNA into the host cell’s genome. Protease: Processes the newly formed viral proteins to create mature infectious virus particles. 5. Matrix: The matrix is a protein layer (composed of p17 proteins) found between the envelope and the capsid. It helps maintain the integrity of the virus particle. 6. Nucleocapsid: This structure surrounds the viral RNA and is composed of p7 proteins, providing additional stability to the RNA strands.  Clinical Findings Symptoms of acute HIV infection are nonspecific and include fatigue, rash, headache, nausea, and night sweats. AIDS is characterized by pronounced suppression of the immune system and development of a wide variety of severe opportunistic infections or unusual neoplasms (especially Kaposi sarcoma). The more serious symptoms in adults are often preceded by a prodrome (“diarrhea and dwindling”) that can include fatigue, malaise, weight loss, fever, shortness of breath, chronic diarrhea, white patches on the tongue (hairy leukoplakia, oral candidiasis), and lymphadenopathy. Disease symptoms in the gastrointestinal tract from the esophagus to the colon are a major cause of debility. With no treatment, the interval between primary infection with HIV and the first appearance of clinical disease is usually long in adults, averaging about 8–10 years. Death occurs about 2 years later.  Plasma Viral Load The amount of HIV in the blood (viral load) is of significant prognostic value. There are continual rounds of viral replication and cell killing in each patient, and the steady-state level of virus in the blood (viral set point) varies from individual to individual during the asymptomatic period. This level reflects the total number of productively infected cells and their average burst size. A single measurement of plasma viral load about 6 months after infection is able to predict the subsequent risk of development of AIDS in men several years later in the absence of treatment  Pediatric AIDS The responses of infected neonates are different from those observed in HIV- infected adults. Pediatric AIDS—acquired from infected mothers—usually presents with clinical symptoms by 2 years of age; death follows in another 2 years. The neonate is particularly susceptible to the devastating effects of HIV because the immune system has not developed at the time of primary infection. Clinical findings may include lymphoid interstitial pneumonitis, pneumonia, severe oral candidiasis, encephalopathy, wasting, generalized lymphade nopathy, bacterial sepsis, hepatosplenomegaly, diarrhea, and growth retardation  Neurologic Disease Neurologic dysfunction occurs frequently in HIV- infected persons. Forty to ninety percent of patients have neurologic symptoms, and many are found during autopsy to have neuropathologic abnormalities. Several distinct neurologic syndromes that occur frequently include subacute encephalitis, vacuolar myelopathy, aseptic meningitis, and peripheral neuropathy  Opportunistic Infections The predominant causes of morbidity and mortality among patients with late-stage HIV infection are opportunistic infections The most common opportunistic infections in untreated AIDS patients include the following: 1. Protozoa: Toxoplasma gondii, Isospora belli, Cryptosporidium species. 2. Fungi: Candida albicans, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Pneumocystis jiroveci. 3. Bacteria: Mycobacterium avium-intracellulare, M tuberculosis, Listeria monocytogenes, Nocardia asteroides, Salmonella species, Streptococcus species. 4. Viruses: Cytomegalovirus, herpes simplex virus, varicella zoster virus, adenovirus, polyomavirus JC virus, hepatitis B virus, hepatitis C virus.  Laboratory Diagnosis Evidence of infection by HIV can be detected in three ways: (1) virus isolation; (2) serologic determination of antiviral antibodies; and (3) measurement of viral nucleic acid or antigens  Prevention, Treatment, and Control A. Antiviral Drugs A growing number of antiviral drugs are approved for treatment of HIV infections Classes of drugs include both nucleoside and nonnucleoside inhibitors of the viral enzyme reverse transcriptase and inhibitors of the viral protease enzyme. B. Vaccines Against HIV A safe and effective vaccine offers the best hope of controlling the worldwide AIDS epidemic. Viral vaccines are typically preventive, ie, given to uninfected individuals to prevent either infection or disease  D. Control Measures Without control by drugs or vaccines, the only way to avoid epidemic spread of HIV is to maintain a lifestyle that minimizes or eliminates the high-risk factors discussed above. No cases have been documented to result from such common exposures as sneezing, coughing, sharing meals, or other casual contacts. E. Health Education Without a vaccine or treatment, the prevention of cases of AIDS relies on the success of education projects involving behavioral changes.  Tuberculosis (TB) and Leprosy (Hansen’s Disease Discusesed in the last year S4  Hepatitis Viruses Viral hepatitis is a systemic disease primarily involving the liver. Most cases of acute viral hepatitis in children and adults are caused by one of the following five agents: hepatitis A virus (HAV), the etiologic agent of viral hepatitis type A (infectious hepatitis); hepatitis B virus (HBV), which is associated with viral hepatitis B (serum hepatitis); hepatitis C virus (HCV), the agent of hepatitis C (common cause of posttransfusion hepatitis); hepatitis D (HDV), a defective virus dependent on co infection with HBV; or hepatitis E virus (HEV),  Hepatitis Type B HBV is classified as a hepadnavirus HBV establishes chronic infections, especially in those infected as infants; it is a major factor in the eventual development of liver disease and hepatocellular carcinoma in those individuals.. Structure and Composition  Hepatitis Type C Clinical and epidemiologic studies and cross- challenge experiments in chimpanzees in the past had suggested that there were several non-A, non- B (NANB) hepatitis agents that, based on serologic tests, were not related to HAV or HBV. The major agent was identified as HCV. HCV is a pos itive- stranded RNA virus, classified as family Flaviviridae, genus Hepacivirus  Laboratory Features Liver biopsy permits a tissue diagnosis of hepatitis. Tests for abnormal liver function, such as serum alanine aminotrans ferase (ALT) and bilirubin, supplement the clinical, pathologic, and epidemiologic findings.  Epidemiology The global distributions of hepatitis A, B, and C infections are shown in Figure  Treatment Treatment of patients with hepatitis is supportive and directed at allowing hepatocellular damage to resolve and repair itself. Only HBV and HCV have specific treatments, and those are only partially effective. Recombinant IFN-α and pegylated IFN-α are currently the therapy of proven benefit in the treatment of patients chronically infected with HBV or HCV. Many who responded clinically and biochemically relapsed after cessation of treatment. Only about 35% of patients with chronic HBV infections have long-lasting remissions, and about 25% of those with chronic HCV infection have a sustained response. IFN-based therapy is associated with many side effects. Several antiviral drugs are available for use against chronic hepatitis infections. With nucleoside and nucleotide analogs, such as lamivudine  Prevention and Control Viral vaccines and protective IG preparations are available against HAV and HBV. Neither type of reagent is currently available to prevent HCV infections  BORRELIA BURGDORFERI AND LYME DISEASE Lyme disease is named after the town of Lyme, Connecticut, where clusters of cases in children were identified. Since 1992, three species of Borrelia have been associated with Lyme disease, Borrelia burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii. All three species cause disease in Europe, but only B burgdorferi is responsible for disease in North America.  The spirochete B. burgdorferi is transmitted to humans by the bite of a small Ixodes tick. The disease has early manifestations with a characteristic skin lesion, erythemamigrans, along with flulike symptoms, and late manifestations often with arthralgia and arthritis  Morphology and Identification A. Typical Organisms B burgdorferi is a spiral organism 20–30 μm long and 0.2–0.3 μm wide. The distance between turns varies from 2 to 4 μm. The organisms have variable numbers (7–11) of endo flagella and are highly motile. B burgdorferi stains readily with acid and aniline dyes and by silver impregnation techniques. B. Culture and Growth Characteristics B burgdorferi grows most readily in a complex liquid medium, Barbour-Stoenner-Kelly medium (BSK II). Rifampin, fosfomycin (phosphonomycin), and amphotericin B can be added to BSK II to reduce the rate of culture contamination by other bacteria and fungi. B burgdorferi has been most easily iso lated from erythema migrans skin lesions; isolation of the organism from other sites has been difficult. The organism can also be cultured from ticks. Because culture of the organism is a complex and specialized procedure with a low diagnostic yield,.  Pathogenesis and Clinical Findings The transmission of B burgdorferi to humans is by injection of the organism in tick saliva or by regurgitation of the tick’s midgut contents Common Symptoms of Lyme Disease 1. Early Localized Stage (3–30 days after tick bite) Erythema Migrans (EM) Rash: The hallmark sign is a red, circular or oval-shaped rash that often expands over time. The rash may have a “bull’s-eye” appearance, with a clear center and a red ring surrounding it. It is usually not itchy or painful, and it appears at the site of the tick bite. Flu-like Symptoms: Fever and chills Fatigue Headache Muscle and joint aches Swollen lymph nodes 2. Early Disseminated Stage (days to weeks after bite) Multiple EM Rashes: Indicating the spread of the bacteria. Neurological Symptoms: Facial palsy (loss of muscle tone or droop on one or both sides of the face). Meningitis-like symptoms (severe headache, neck stiffness). Peripheral neuropathy (numbness, tingling in hands or feet). Cardiac Symptoms: Lyme carditis (irregular heartbeats or palpitations). Dizziness or shortness of breath. Pain and Swelling in Large Joints (e.g., knees). 3. Late Disseminated Stage (months to years after bite, if untreated) Arthritis: Severe joint pain and swelling, especially in large joints like the knees. Chronic Neurological Problems: Cognitive issues (memory problems, difficulty concentrating). Chronic pain or numbness. Sleep disturbances. Severe Fatigue: Persistent exhaustion that doesn’t improve with rest. Other Potential Symptoms Sensitivity to light. Vision changes. In rare cases, Lyme disease can affect the eyes, liver (hepatitis), or lead to severe neurological complications (encephalopathy).  Diagnostic Laboratory Tests A. Specimens Blood is obtained for serologic tests. CSF or joint fluid can be obtained, but culture usually is not recommended. B. Smears B. burgdorferi has been found in sections of biopsy specimens, but examination of stained smears is an insensitive method for diagnosis of Lyme disease. C. Culture Culture is generally not performed because it takes 6–8 weeks to complete and lacks sensitivity. D. Nucleic Acid Amplification Methods The PCR assay has been applied to detection of B. burgdorferi DNA in many body fluids. It is rapid, sensitive, and specific,  Treatment Early infection, either local or disseminated, should be treated with doxycycline, amoxicillin, or cefuroxime axetil for 14–21 days. Treatment relieves early symptoms and promotes resolution of skin lesions. Doxycycline may be more effective than amoxicillin in preventing late manifestations. Established arthritis may respond to prolonged therapy with doxycycline or amoxicillin orally or penicillin G or ceftriaxone intravenously  Pulmonary aspergillosis Pulmonary aspergillosis refers to a spectrum of lung diseases caused by inhalation of Aspergillus species, a type of common fungus found in the environment. It primarily affects people with weakened immune systems or underlying lung conditions. There are different forms of pulmonary aspergillosis, each with its own set of symptoms and severity  Morphology and Identification Aspergillus species grow rapidly, producing aerial hyphae that bear characteristic conidial structures: long conidiophores with terminal vesicles on which phialides produce basipetal chains of conidia  Types of Pulmonary Aspergillosis 1. Allergic Bronchopulmonary Aspergillosis (ABPA A hypersensitivity reaction to Aspergillus, usually seen in patients with asthma or cystic fibrosis. Symptoms: Wheezing Coughing (with mucus plugs or blood) Shortness of breath Fever Increased asthma symptoms 2. Chronic Pulmonary Aspergillosis (CPA): Long-term infection of the lungs, often occurring in people with pre-existing lung diseases like tuberculosis or chronic obstructive pulmonary disease (COPD). Symptoms: Chronic cough (often with blood-tinged sputum) Unintentional weight loss Fatigue Shortness of breath Chest pain 3. Aspergilloma (Fungal Ball): A mass of Aspergillus hyphae, mucus, and cellular debris that forms in lung cavities, often seen in patients with prior lung damage. Symptoms: Hemoptysis (coughing up blood) is the most common symptom. Persistent cough Mild to severe chest pain 4. Invasive Pulmonary Aspergillosis (IPA): A severe form of the disease that occurs in people with severe immune suppression (e.g., organ transplant recipients, cancer patients). Symptoms: High fever Severe cough (may produce blood) Chest pain Difficulty breathing Generalized weakness or fatigue In severe cases, it can spread to other organs, causing systemic infection.  Diagnosis of Pulmonary Aspergillosis Imaging: Chest X-ray or CT scans may show characteristic signs such as aspergillomas, cavitations, or nodules. Serology and Allergy Tests: Blood tests to detect specific antibodies against Aspergillus or markers of allergic reactions (IgE levels). Sputum Culture: Analysis of sputum samples to identify Aspergillus species. Biopsy: In some cases, a lung tissue biopsy may be necessary for confirmation. Thank you