The human immunodeficiency virus (HIV) is a retrovirus that causes AIDS (acquired immune deficiency syndrome). The retrovirus primarily attacks the immune defense system, making the body extremely vulnerable to opportunistic infections, including fungal infections. Opportunistic infections occur in individuals who have weakened immune systems.
HIV is transmitted from person to person via bodily fluids, including blood, semen, vaginal discharge, and breast milk. Therefore, it can be spread by sexual contact with an infected person, by sharing needles/syringes with someone who is infected, through breastfeeding, during vaginal childbirth or, less commonly (and rare in countries where blood is screened for HIV antibodies), through transfusions with infected blood. HIV has been found in saliva and tears in very low concentrations in some AIDS patients. However, contact with saliva, tears, or sweat has never been shown to result in transmission.
Currently, there is no cure for HIV/AIDS. Patients receive antiretroviral drugs that help suppress the virus. These drugs do not reduce the risk of transmitting the disease to someone else.
HIV can infect and kill many different types of cells in the body but the primary targets are the CD4 T-cells, which are white blood cells that helps coordinate the immune system's response to infections and diseases.
The first stage of HIV, known as the primary or acute infection, is the most infectious stage of the disease and it typically lasts several weeks. During this phase, the virus replicates rapidly, which leads to an abundance of the virus in the bloodstream and a drastic decline in the number of CD4 T-cells.
The CD8 T-cells (cells that kill abnormal or infected body cells) are then activated to destroy HIV-infected cells and antibodies are produced. An estimated 80-90% of HIV patients experience flu-like symptoms during this stage.
The next stage, called clinical latency, may last anywhere from two weeks to 20 years. During this phase, HIV is active in the lymph nodes, where large amounts of the virus become trapped. The surrounding tissues, which contain high levels of CD4 T-cells, may also become infected. The virus accumulates in infected cells and in the blood as free virus.
Patients progress to AIDS (acquired immune deficiency syndrome) when their CD4 cell counts drop below 200 cells per microliter of blood. Healthy individuals have a CD4 cell count between 600 and 1,200 cells per microliter of blood.
Fungal infections are among some of the most common opportunistic infections (OIs) that occur in HIV patients. Most people have been exposed to the disease-causing fungi because they are everywhere. However, infections only occur in individuals who have weakened immune systems that cannot prevent the fungus from growing. Common fungal infections include Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii pneumonia or PCP), pulmonary aspergillosis, cryptococcal meningitis, and candidiasis. Most of these infections primarily affect the lungs as the fungus spores are inhaled.
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pneumocystis jiroveci pneumonitis
Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii or PCP) is the most common opportunistic infection among HIV patients. Originally, researchers thought a one-cell organism called Pneumocystis carinii caused the disease, but it has been discovered that a fungus called Pneumocystis jiroveci is the cause. The condition is still commonly referred to as Pneumocystis carinii pneumonia (PCP).
According to the U.S. Centers for Disease Control and Prevention (CDC), PCP is considered an AIDS-defining illness. This means that when HIV-infected patients develop PCP, their condition has progressed to AIDS.
This disease almost always affects the lungs causing a type of pneumonia. The first signs of PCP are difficulty breathing, fever, and a dry cough. Other common symptoms include chest discomfort, weight loss, chills, spitting up blood (rare), rapid breathing, fast heart rate, cyanosis (bluish discoloration of the skin), nasal flaring, and intercostal retractions (visible use of muscles between the ribs that indicates labored breathing). During a physical examination, a healthcare provider may hear mild crackles (bubbling or rattling sounds that occur when air moves through fluid-filled airways in the lungs).
Historically, mortality ranged from 20-40%, depending on the severity of the disease when it was diagnosed. However, mortality rates have declined between 10-20%. Today, PCP is almost entirely preventable and it may be treated effectively with antifungal medications. Unfortunately, PCP is still common in patients who have been infected with HIV for a long time prior to initiation of antiretroviral therapy (ART). In fact, 30-40% of HIV patients develop PCP if they begin ART when their CD4 cell counts are about 50 cells per microliter of blood.
A diagnosis can only be confirmed after the fungus is identified. Samples may be taken from the patient's sputum or via bronchoalveolar lavage (BAL) or lung biopsy. During a BAL, a bronchoscope (thin, flexible tube) is passed through the mouth or nose into the lungs. Saline is then squirted into a small part of the lung and then collected for analysis. A lung biopsy is the most invasive test and it should only be performed in rare cases when a BAL is non-diagnostic. A BAL may be non-diagnostic if it is not performed correctly.
TMP/SMX (Bactrim® or Septra®) is the most effective treatment for PCP. The drug is a combination of two antibiotics, trimethoprim (TMP) and sulfamethoxazole (SMX), which work synergistically to kill the fungus. Patients typically receive treatment for the rest of their lives to prevent the infection from recurring. Allergic reactions to the drug usually cause a skin rash and sometimes a fever.
The Aspergillus fungus causes aspergillosis pulmonary infections. Although there are more than 100 Aspergillus species, most human illnesses are caused by Aspergillus fumigatus or Aspergillus niger or, less frequently, Aspergillus flavus or Aspergillus clavatus.
According to the U.S. Centers for Disease Control and Prevention (CDC), aspergillosis is not considered an AIDS-defining illness. This means that patients who develop aspergillosis do not necessarily have AIDS.
There are four main types of aspergillosis: allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing Aspergillus pneumonia (CNAP), aspergilloma, and invasive aspergillosis. ABPA is a hypersensitive reaction to A. fumigatus, which causes inflammation of the airways and air sacs of the lungs. CNAP is a rare condition that usually occurs in patients who have weakened immune systems. An aspergilloma is a fungus ball (mycetoma) that develops in a preexisting lung cavity (abnormal space between the membranes that line the lungs). Invasive aspergillosis is a rapidly progressive, often fatal infection that occurs in patients who have extremely weakened immune systems.
When a human host inhales the fungus spores, the organism enters the lungs. Macrophages (white blood cells that kill microorganisms that enter the body) and neutrophils (white blood cells that destroy foreign substances that enter the body) will engulf the invading fungus to prevent infection.
However, many species of Aspergillus produce toxic metabolites that may prevent macrophages and neutrophils from engulfing them. Individuals who are taking corticosteroids or have immunodeficiencies (like HIV/AIDS) have impaired macrophage and neutrophil function, making it even more difficult to fight off the fungus. Consequently, HIV patients are unable to fight off the invading fungus and therefore suffer from pulmonary infections.
Although this infection primarily affects the lungs, it may spread to other organs. In such cases, the infection may cause endophthalmitis (inflammation of the eye that is a medical emergency), endocarditis (infection of the lining of the heart), and abscesses (collection of pus) in the heart muscle, kidney, liver, spleen, soft tissue (fat, muscle, blood vessels, tendons, and ligaments), and bone.
Common symptoms include fever, cough, dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain, hypoxemia (low levels of oxygen in the blood), and sometimes hemoptysis (blood in sputum).
Aspergillosis is diagnosed once the fungus has been identified in the patient's tissue. Procedures and tests, such as a sputum sample analysis, bronchoalveolar lavage, lung biopsy, chest X-ray, and computerized tomography (CT) scan, are performed to identify the fungus and to assess the tissue damage.
Treatment varies depending on the specific type of aspergillosis. An antifungal called voriconazole (Vfend®) is commonly used to treat pulmonary aspergillosis. Other antifungals, such as itraconazole (Sporanox®), caspofungin (Cancidas), or amphotericin B formulations (Fungilin®, Fungizone®, Abelcet®, AmBisome®, Fungisome®, Amphocil®, and Amphotec®), have also been used.
Cryptococcus neoformans, a type of yeast found worldwide, can cause pulmonary and central nervous system (CNS) infections that can potentially spread to other areas of the body. This infection is called cryptococcosis. HIV/AIDS patients are especially vulnerable to developing the infection.
If the infection spreads from the lungs to the CNS (brain and spinal cord) of an HIV patient, the condition is considered an AIDS-defining illness. This means the patient's condition has progressed to AIDS.
Most infections develop after the yeast has been inhaled into the lungs. The fungus strongly resists phagocytosis. This means the immune system cells have to work hard to engulf the organism.
Cryptococcosis usually starts with a pulmonary (lung) infection, which then spreads to the CNS. If left untreated, the infection may continue to spread to other organs in the body, including the skin, prostate and medullary cavity of the bones. Common symptoms of pulmonary involvement include fever, general feeling of discomfort, dry cough, pain in the membrane surrounding the lungs, and rarely, hemoptysis (blood in sputum).
Common symptoms of CNS involvement include symptoms such as headache, altered mental status (such as personality changes, confusion, lethargy, and reduced alertness), coma, nausea, and vomiting. If the infection spreads to the skin, it may cause papules, pustules, nodules, ulcers, or draining sinuses. Umbilicated papules in HIV patients may look similar to a chicken pox infection. If it spreads to the bones, the infection may cause bone lesions.
The diagnosis is made on the basis of a series of tests, including a cerebrospinal fluid (CSF) culture and positive identification of the yeast.
Initially, amphotericin B (Amphocin® or Fungizone®), a type of antifungal medication, is administered at 0.7-1 milligrams/kilogram/day for two weeks, with or without two weeks 100 milligrams/kilogram/day of flucytosine. Once initial treatment is completed, a maintenance therapy of 200-400 milligrams/day of fluconazole for life is recommended as a preventative measure against future Cryptococcus infections.
candidiasis (oral thrush)
Mucocutaneous candidiasis is an opportunistic infection caused by the fungus Candida albicans that may affect the mouth (oral candidiasis, oral thrush), esophagus (esophageal candidiasis), or vagina (vulvovaginal candidiasis, yeast infections).
The Candida albicans fungus, which is responsible for the development of candidiasis, is found almost everywhere in the environment. Most people have small amounts of Candida albicans present in their mouths and/or vagina at any given time, but healthy individuals are able to prevent the fungus from multiplying and causing an infection.
Oral candidiasis, commonly known as oral thrush, usually develops in HIV patients once their CD4 cell count drops below 350. Candidiasis causes an inflammation and thick white coating and lesions on the mucous membranes of the mouth, including the cheeks, roof of the mouth, gums, tonsils and tongue. The lesions are often painful and may bleed slightly when rubbed or scraped. While oral thrush is the least serious of the fungal infections associated with HIV, it may indicate that a patient's HIV condition is worsening. The oral infection can progress to esophageal candidiasis, which occurs when thrush spreads to the esophagus.
Esophageal candidiasis typically occurs when the HIV patient's CD4 cell counts are 200 or less. Esophageal candidiasis is the only type of candidiasis that is considered an AIDS-defining illness. This means that when HIV-infected patients develop esophageal candidiasis, their condition has progressed to AIDS.
Vaginal candidiasis (yeast infection) is common in both immunocompetent and immunocompromised individuals. Researchers estimate that about 75% of all women are likely to have at least one vaginal Candida infection during their lifetime, and up to 45% experience two or more. Individuals who become pregnant, take high-estrogen oral contraceptives (like birth control pills), have uncontrolled diabetes mellitus, wear tight-fitting clothes, receive antibiotic therapy, and individuals who have sexually transmitted diseases have an increased risk of developing yeast infections. Common symptoms include itching, watery or curd-like vaginal discharge that is white in color, vaginal erythema (reddening of the skin), dyspareunia (pain during sexual intercourse), external dysuria (painful urination), swollen labia and vulva, and vaginal lesions.
In most cases, diagnoses of candidiasis infections can be determined after a physical examination. If a diagnosis is uncertain, the physician may scrape surface cells of the mouth, esophagus, or vagina (depending on where symptoms are) or culture a tissue sample to determine whether the fungus is present.
Candidiasis infections are treatable. HIV patients who have candidiasis infections usually receive treatment with antifungals to clear the infection. Amphotericin B, fluconazole, ketoconazole, and nystatin are the drugs most commonly used to treat oral and esophageal candidiasis. Treatment generally lasts 10 to 14 days. Some of these medications may cause liver damage. Therefore, blood tests should be performed regularly during. Yeast infections may be treated with over-the-counter medications such as butoconazole (Femstat®), clotrimazole (Gyne-Lotrimin®), miconazole (Monistat 3®), tioconazole (Vagistat®, Trosyd®), and terconazole (Vagistat-1®). Treatment generally lasts one to seven days.