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Histoplasmosis

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Description: Histoplasmosis is a fungal infection caused by inhaling spores of the Histoplasma capsulatum fungus, often found in bird and bat droppings.
Type: Histoplasmosis is an infectious disease caused by the fungus Histoplasma capsulatum. It is not a genetic disease and therefore does not involve genetic transmission. Instead, it is primarily acquired through the inhalation of spores from contaminated soil, often in areas with a high concentration of bird or bat droppings.
Signs And Symptoms: If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can resemble tuberculosis; disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Lesions often left calcification nodules as they are healed.Presumed ocular histoplasmosis syndrome causes chorioretinitis, where the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to Histoplasma is controversial. Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.
Prognosis: About 90% of patients with normal immune systems regain health without any intervention. Less than 5% need serious treatments.
Onset: Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. The onset of symptoms typically occurs between 3 to 17 days after exposure to the fungal spores. The severity of symptoms can vary, ranging from mild, flu-like symptoms to more severe respiratory issues, and in rare cases, it can become a chronic, disseminated infection affecting multiple organs.
Prevalence: Histoplasmosis is a fungal infection caused by inhalation of spores of the fungus Histoplasma capsulatum. It is most prevalent in regions of North America, particularly in the Ohio and Mississippi River valleys. The prevalence varies, but it is estimated that up to 80% of individuals in endemic areas may have been exposed to the fungus at some point, although not all exposed individuals develop symptoms. The disease can manifest in various forms, ranging from asymptomatic to severe disseminated disease, particularly in immunocompromised individuals.
Epidemiology: H. capsulatum is found throughout the world. It is endemic in certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River. The humidity and acidity patterns of soil are associated with endemicity. Bird and bat droppings in soil promote the growth of Histoplasma. Contact with such soil aerosolizes the microconidia, which can infect humans. It is also common in caves in Southern and East Africa. Positive histoplasmin skin tests occur in as many as 90% of the people living in areas where H. capsulatum is common, such as the eastern and central United States.In Canada, the St. Lawrence River Valley is the site of the most frequent infections, with 20–30% of the population testing positive. A review of reported cases in 2018 showed disease presence throughout Southeast Asia, In India, the Gangetic West Bengal is the site of most frequent infections, with 9.4% of the population testing positive. H. c. capsulatum was isolated from the local soil proving endemicity of histoplasmosis in West Bengal.In non-endemic countries, 40-50% of histoplasmosis cases are diagnosed in immunocompromised patients (HIV/AIDS, transplanted patients, cancer patients).
Intractability: Histoplasmosis is typically not considered intractable. It is a fungal infection caused by Histoplasma capsulatum. Most cases are mild and self-limiting, particularly in healthy individuals. However, it can be severe and potentially intractable in immunocompromised patients, such as those with HIV/AIDS or those undergoing immunosuppressive therapy. Effective antifungal treatments are available, such as itraconazole, that can manage and often cure the disease.
Disease Severity: Histoplasmosis severity can vary. It ranges from mild, self-limiting respiratory illness to severe, disseminated disease, especially in immunocompromised individuals.
Healthcare Professionals: Disease Ontology ID - DOID:1731
Pathophysiology: **Pathophysiology of Histoplasmosis:**

Histoplasmosis is caused by the inhalation of microconidia (spores) from the fungus *Histoplasma capsulatum*. This fungus is found in soil, often contaminated with bird or bat droppings. The spores are aerosolized and inhaled, primarily affecting the lungs.

Once inhaled, the microconidia are phagocytosed by alveolar macrophages, where they convert to the yeast form. The yeast form can survive and replicate within macrophages by inhibiting phagosome-lysosome fusion. The infected macrophages can disseminate the yeast through the lymphatic system to other organs and tissues, particularly in immunocompromised individuals.

The immune response to *Histoplasma* involves both innate and adaptive immunity. T-cells, particularly TH1 cells, play a crucial role by secreting cytokines like interferon-gamma (IFN-γ), which activates macrophages to kill the yeast. In most immunocompetent individuals, this leads to the formation of granulomas that contain the infection.

In immunocompromised individuals, such as those with HIV/AIDS, the containment of the infection may fail, leading to disseminated histoplasmosis, which can affect multiple organs and be life-threatening.
Carrier Status: Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. Humans cannot be carriers in the traditional sense, as the disease is acquired by inhaling the fungal spores from the environment. Once infected, some people may remain asymptomatic while the infection resides in their bodies, which can reactivate later, especially if their immune system becomes compromised. There is no "carrier status" like in some bacterial or viral infections, but individuals can have a latent infection without symptoms.
Mechanism: Histoplasmosis is a fungal infection caused by inhaling the spores of Histoplasma capsulatum.

**Mechanism:**
1. **Inhalation and Initial Infection**: When spores are inhaled, they settle in the alveoli of the lungs.
2. **Transformation and Immune Response**: The spores transform into yeast form at human body temperature. Macrophages in the lungs phagocytose the yeast cells but often fail to kill them.
3. **Dissemination**: The yeast cells can multiply within macrophages and travel through the lymphatic system and bloodstream to other parts of the body, potentially leading to disseminated histoplasmosis.

**Molecular Mechanisms:**
1. **Adhesion**: Histoplasma capsulatum spores adhere to alveolar macrophages via surface receptors.
2. **Survival in Macrophages**: The yeast cells modulate the pH of phagolysosomes to inhibit the degradative functions of macrophages. They also secrete enzymes and other factors that neutralize reactive oxygen species.
3. **Iron Acquisition**: The fungus expresses siderophores and other iron-binding proteins to acquire iron crucial for its growth, particularly within the iron-limited environment of the macrophage.
4. **Immune Evasion**: The yeast cells can modulate the host immune response by altering cytokine profiles and impairing antigen presentation, which helps in evading the immune system.

Understanding these mechanisms is crucial for developing targeted therapies and improving the management of histoplasmosis.
Treatment: In the majority of immunocompetent individuals, histoplasmosis resolves without any treatment. Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole.Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients who might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function. Liposomal amphotericin B is better at treating people with progressive disseminated Histoplasmosis and underlying HIV when compared to deoxycholate amphotericin B. Meanwhile, fluconazole performs poorly when compared to other azoles.Treatment with itraconazole must continue for at least a year in severe cases, while in acute pulmonary Histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function.
Compassionate Use Treatment: Histoplasmosis is typically treated with antifungal medications, and the need for compassionate use treatment or off-label/experimental treatments usually arises in severe or refractory cases. Here are some relevant details:

1. **Compassionate Use Treatment**:
- For patients who do not respond to standard treatments or cannot tolerate them, compassionate use of investigational drugs may be considered. This involves the use of a new, unapproved drug outside of a clinical trial when no other treatment options are available.

2. **Off-Label Treatments**:
- Occasionally, healthcare providers may prescribe medications off-label. For example, posaconazole, usually used for other fungal infections, might be prescribed for histoplasmosis in tough cases where first-line treatments are ineffective.

3. **Experimental Treatments**:
- Clinical trials may offer access to new treatments. For instance, newer antifungal agents or adjunctive therapies that modulate the immune system to enhance the body's ability to fight the infection may be explored.

All treatment decisions should be guided by a healthcare professional with careful consideration of the individual patient's condition and needs.
Lifestyle Recommendations: For histoplasmosis, lifestyle recommendations include the following:

1. **Avoid Exposure**: Stay away from areas known to be contaminated with Histoplasma capsulatum, such as locations with bird or bat droppings, especially in places like caves, chicken coops, or old buildings.

2. **Protective Measures**: If you must be in areas where the fungus is likely present, wear protective gear such as masks or respirators to reduce inhalation of the fungal spores.

3. **Hygiene**: Practice good hygiene by thoroughly washing hands after potential exposure and before eating.

4. **Handling Soil Safely**: Wet the soil before disturbing it to reduce the amount of dust that might contain fungal spores.

5. **Stay Informed**: Be aware of regional advisories if you live in or visit areas where histoplasmosis is endemic, such as the central and eastern United States, parts of Central and South America, Africa, Asia, and Australia.

These recommendations aim to minimize the risk of contracting or exacerbating histoplasmosis.
Medication: The primary medications used to treat histoplasmosis are antifungal agents. The most commonly prescribed include:

1. **Itraconazole**: Often the first line of treatment for mild to moderate histoplasmosis.
2. **Amphotericin B**: Used for severe or disseminated infections, often initiated in a hospital setting.

Treatment duration typically ranges from a few months to a year, depending on the severity and patient response.
Repurposable Drugs: For histoplasmosis, potential repurposable drugs include:

1. Itraconazole: An antifungal medication commonly used as the first-line treatment for mild to moderate histoplasmosis.
2. Amphotericin B: Often used for severe cases, especially in immunocompromised patients.
3. Posaconazole and Voriconazole: These antifungal agents have shown effectiveness and may be considered in certain cases, although they're not first-line treatments.

Please consult with a healthcare provider for personalized medical advice.
Metabolites: In the context of histoplasmosis, the major metabolites of interest include those involved in the pathogenicity of the Histoplasma capsulatum fungus, such as siderophores (e.g., ferricrocin) which facilitate iron acquisition, and various enzymes and lipid molecules that aid in survival and replication within the host. Additionally, histoplasmosis can lead to the production of host metabolites associated with inflammatory and immune responses. Specific nanomaterials or nanoparticles (nan) have been explored in research for targeted drug delivery and diagnostic purposes in treating and identifying histoplasmosis, taking advantage of their small size and ability to be functionalized for specific interactions.
Nutraceuticals: Histoplasmosis is primarily managed with antifungal medications, but there isn't significant evidence supporting the use of nutraceuticals to treat or prevent the disease. Focus remains on medical treatments and preventative measures to avoid exposure to Histoplasma capsulatum. Always consult with healthcare providers for appropriate care.
Peptides: Histoplasmosis is a fungal infection caused by inhaling spores of the fungus Histoplasma capsulatum. Peptides from this fungus play a role in the immune response and can be studied to develop diagnostic tools or treatments. The "nan" might refer to nanoparticles, which could be used to improve drug delivery systems for antifungal medications targeting Histoplasma capsulatum.