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 known 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.
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, it is estimated that mortality rates have declined between 10 and 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 (Fungizone©, Abelcet©, AmBisome©, 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.
Good scientific evidence
: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Evidence from human trials suggests that zinc pyrithione shampoo may be an effective treatment for tinea versicolor fungal infections of the scalp. Side effects were not noted. Additional research is needed before a strong recommendation can be made.
Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used since studies cannot rule out the possibility of harm to the fetus.
Unclear or conflicting scientific evidence
: Limited available human study used 8-methoxypsoralen (8-MOP), a photoreactive plant compound from bishopsweed, for the treatment of tinea versicolor. Clinical studies are needed before a conclusion can be made.
Use cautiously in patients with photosensitivity as bishop's weed may be photoreactive, and cause phototoxic skin damage, phototoxic dermatitis, and pigmentary retinopathy. Use cautiously in patients with bleeding disorders or taking anticoagulants, NSAIDs/anti-platelet agents, or herbs or supplements that increase risk of bleeding because bishop's weed may have additive effects and increase the risk of bleeding. Use cautiously in patients taking drugs or herbs or supplements metabolized by cytochrome P450 as bishop's weed may increase the effects of these agents. Use cautiously in patients with eye disorders, as bishop's weed may cause ocular toxicity. Avoid in patients with known allergy/hypersensitivity to bishop's weed, its constituents, or members of the Apiaceae family.
: Limited available human study found promising results using the oil of bitter orange for treatment of fungal infections. However, due to methodological weakness of this research, further evidence is needed to confirm these results.
Avoid if allergic or hypersensitive to bitter orange or any members of the Rutaceae family. Avoid with heart disease, narrow-angel glaucoma, intestinal colic, or long QT interval syndrome. Avoid if taking anti-adrenergic agents, beta-blockers, QT-interval prolonging drugs, monoamine oxidase inhibitors (MAOIs), stimulants, or honey. Use cautiously with headache, hyperthyroidism (overactive thyroid), or if fair-skinned. Avoid if pregnant or breastfeeding.
: There is currently a lack of available evidence to support the use of cinnamon for AIDS patients with advanced oral candidiasis. More study is needed in this area.
Avoid if allergic or hypersensitive to cinnamon, its constituents, members of the Lauraceae family, or Balsam of Peru. Use cautiously if prone to atopic reactions or if taking cytochrome P450 metabolized agents, anticoagulants (blood thinners), insulin or blood sugar-altering medications, antibiotics, or cardiovascular agents. Avoid if pregnant or breastfeeding.
: Limited laboratory research has examined the antifungal activity of cranberry. Reliable human studies supporting the use of cranberry for fungal infections are currently lacking. Further research is warranted in this area.
Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.
: Garlic is used both medicinally and as a food spice. Several studies describe the use of garlic as a topical antifungal to treat fungal infections of the skin, including yeast infections. More research is needed in this area.
Use cautiously as garlic can cause severe burns and rash when applied to the skin of sensitive individuals.
Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae
(lily) family (e.g. hyacinth, tulip, onion, leek, or chive). Avoid with a history of bleeding problems, asthma, diabetes, low blood pressure, or thyroid disorders. Stop using supplemental garlic two weeks before and immediately after dental/surgical/diagnostic procedures with bleeding risks. Avoid in supplemental doses if pregnant or breastfeeding.
: In clinical study, an extract of pomegranate was shown to be as effective as a commonly used oral gel when used topically to treat candidiasis associated with denture stomatitis (mouth sores). Additional study is needed to confirm pomegranate's antifungal effects.
Avoid if allergic or hypersensitive to pomegranate. Avoid with diarrhea or high or low blood pressure. Avoid taking pomegranate fruit husk with oil or fats to treat parasites. Pomegranate root/stem bark should only be used under the supervision of a qualified healthcare professional. Use cautiously with liver damage or liver disease. Pomegranate supplementation may be unsafe during pregnancy when taken by mouth. The bark, root, and fruit rind may cause menstruation or uterine contractions. Avoid if breastfeeding due to a lack of scientific data.
: Early research suggests that cheese containing probiotics may help reduce the risk of a fungal mouth infection, called thrush, in the elderly. More research is needed in this area.
Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.
: Propolis is a natural resin created by bees to make their hives. Propolis is made from the buds of conifer and poplar trees and combined with beeswax and other bee secretions. In human study, a commercial propolis ethanol extract from Brazil, formulated to ensure physical and chemical stability, was found to inhibit fungal infections of the mouth, such as oral candidiasis. Additional research is needed to confirm these findings.
Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
Seaweed, kelp, bladderwrack
: Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, and
it is often combined with bladderwrack in kelp preparations. Laboratory research suggests that bladderwrack may have antifungal activity. However, reliable human studies to support this use are currently lacking in the available literature.
Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
: Selenium is a mineral found in soil, water, and some foods. Commercially available 1% selenium sulfide shampoo has been reported as equivalent to sporicidal therapy in the adjunctive treatment of the yeast infection tinea capitis. However, further high-quality evidence is warranted.
Selenium sulfide shampoo has also been studied as a possible treatment for tinea versicolor. However, research results are inconclusive.
Avoid if allergic or hypersensitive to products containing selenium. Avoid with a history of non-melanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
Tea tree oil
: Although tea tree oil has been found to have activity against several fungus species in laboratory study, there is currently insufficient human evidence to determine if it is an effective topical treatment for onychomycosis, tinea pedis (athlete's foot), or thrush (oral Candida albicans).
Tea tree oil may be toxic when taken by mouth and therefore, should not be swallowed. Avoid if allergic to tea tree oil or plants of the Myrtle (Myrtaceae) family, Balsam of Peru, or benzoin. Use cautiously with a history of eczema. Avoid if pregnant or breastfeeding.
: Thyme has been used medicinally for thousands of years. Beyond its common culinary application, it has been recommended for many indications based on proposed antimicrobial, antitussive, spasmolytic, and antioxidant activity. Thyme essential oil and thymol have been shown to have antifungal effects. Topical thymol has been used traditionally to treat paronychia (skin infection around a finger or toenail) and onycholysis (fungal nail infection). Currently, there is insufficient reliable human evidence to recommend for or against the use of thyme or thymol as a treatment for fungal infections.
Avoid if allergic or hypersensitive to thyme, members of the Lamiaceae (mint) family, any component of thyme, or rosemary (Rosmarinus officinalis). Avoid oral ingestion or non-diluted topical application of thyme oil due to potential toxicity. Avoid topical preparations in areas of skin breakdown or injury or in atopic patients due to multiple reports of contact dermatitis. Use cautiously with gastrointestinal irritation or peptic ulcer disease due to anecdotal reports of gastrointestinal irritation. Use cautiously with thyroid disorders due to observed anti-thyrotropic effects in animal research of the related species Thymus serpyllum. Avoid if pregnant or breastfeeding.
Traditional or theoretical uses lacking sufficient evidence
: The aconite plant grows in rocky areas. It is often found in the mountainous woodlands of many parts of Europe, especially France, Austria, Germany, and Denmark. Although aconite has been suggested as a potential antifungal agent, human studies are currently lacking.
Aconite is highly toxic and is not safe for human consumption. Avoid with heart disease, heart dysfunction, irregular heartbeat, hemodynamic instability (abnormal blood flow), gastrointestinal disorders, ulcers, reflux esophagitis, ulcerative colitis, spastic colitis, or diverticulosis. Use cautiously with diabetes or suicidal tendencies. Avoid if younger than 18 years old. Avoid if pregnant or breastfeeding.
: Shiitake mushrooms were originally grown on natural oak logs found in Japan. Today, they are available in the United States. In laboratory study, lentin, isolated from Lentinula edodes, inhibited mycelial growth in several fungal species including Candida albicans,
Physalospora piricola, Botrytis cinerea, and Mycosphaerella arachidicola. However, clinical studies are needed to determine if shiitake is an effective antifungal agent in humans.
Avoid if allergic or hypersensitive to shiitake mushrooms. Avoid if pregnant or breastfeeding.
Most fungal infections are less likely to develop in individuals who have healthy immune systems. Therefore, patients who have HIV/AIDS should receive highly active antiretroviral therapy (HAART), which suppresses HIV and subsequently boosts the body's immune system.
Preventative antifungal therapy and the use of laminar air flow (LAF) or high-efficiency particulate air (HEPA) filters in hospital rooms of patients who receive bone marrow transplants and other high-risk patients may prevent fungal infections. These filters help trap the microscopic fungal spores before they are able to circulate in the air.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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- Centers for Disease Control and Prevention (CDC). www.cdc.gov. Accessed May 20, 2009.
- HIV InSite. www.hivinsite.org.
- National Institute of Allergy and Infectious Diseases. www.niaid.nih.gov. Accessed May 20, 2009.
- Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed May 20, 2009.
- Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group. Medicine (Baltimore). 2000 Jul;79(4):250-60. .View abstract
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