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Tularemia

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Description: Tularemia is a rare infectious disease caused by the bacterium Francisella tularensis, often transmitted through tick and insect bites or contact with infected animals.
Type: Tularemia is a bacterial infection caused by the bacterium *Francisella tularensis*. It is not genetically transmitted; it is typically acquired through contact with infected animals, bites from ticks, deer flies, or through exposure to contaminated water, soil, or aerosols.
Signs And Symptoms: Depending on the site of infection, tularemia has six characteristic clinical variants: ulceroglandular (the most common type representing 75% of all forms), glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal.The incubation period for tularemia is 1 to 14 days; most human infections become apparent after three to five days. In most susceptible mammals, the clinical signs include fever, lethargy, loss of appetite, signs of sepsis, and possibly death. Nonhuman mammals rarely develop the skin lesions seen in people. Subclinical infections are common, and animals often develop specific antibodies to the organism. Fever is moderate or very high, and tularemia bacilli can be isolated from blood cultures at this stage. The face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may suppurate (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever.
Prognosis: Since the invention of antibiotics, the rate of death associated with tularemia has decreased from 60% to less than 4%.
Onset: Tularemia typically has an onset of symptoms ranging from 3 to 5 days after exposure, but it can vary from 1 to 14 days.
Prevalence: Tularemia is a relatively rare infectious disease caused by the bacterium *Francisella tularensis*. Its prevalence is low globally, with a higher incidence in rural and semi-rural areas of North America, parts of Europe, and Asia. Outbreaks are sporadic, and the disease remains uncommon. People who have regular exposure to wildlife or tick-infested regions are at a higher risk of contracting tularemia.
Epidemiology: Tularemia is most common in the Northern Hemisphere, including North America and parts of Europe and Asia. It occurs between 30° and 71° north latitude.In the United States, although records show that tularemia was never particularly common, incidence rates continued to drop over the course of the 20th century. Between 1990 and 2000, the rate dropped to less than 1 per one million, meaning the disease is extremely rare in the United States today.In Europe, tularemia is generally rare, though outbreaks with hundreds of cases occur every few years in neighboring Finland and Sweden. In Sweden over a period from 1984 to 2012 a total of 4,830 cases of tularemia occurred (most of the infections were acquired within the country). About 1.86 cases per 100,000 persons occur each year with higher rates in those between 55 and 70.
Intractability: Tularemia is not considered intractable. It can be effectively treated with antibiotics such as streptomycin, gentamicin, doxycycline, or ciprofloxacin. Early diagnosis and appropriate treatment are crucial for a good prognosis.
Disease Severity: Tularemia is a potentially serious infectious disease caused by the bacterium Francisella tularensis. It can range in severity from mild to life-threatening, depending on factors such as the form of the disease and the timeliness of treatment. Without prompt antibiotic treatment, tularemia can lead to severe complications and may be fatal.
Healthcare Professionals: Disease Ontology ID - DOID:2123
Pathophysiology: Tularemia, also known as rabbit fever, is caused by the bacterium Francisella tularensis. The pathophysiology involves the bacterium entering the body through skin, mucous membranes, or inhalation. Once inside the body, F. tularensis is phagocytosed by macrophages but survives and replicates within these cells. This leads to local tissue necrosis and the formation of granulomas. The infection can spread to lymph nodes and subsequently to other organs, causing systemic symptoms. The immune response involves both humoral and cell-mediated pathways, but the bacteria's ability to evade the immune system complicates the disease course.
Carrier Status: Tularemia is primarily a zoonotic disease, meaning it is transmitted from animals to humans. It does not involve a carrier status in humans, as humans are incidental hosts and do not carry or transmit the disease to others. The main carriers are wild animals, particularly rabbits, hares, and rodents, as well as arthropods like ticks and deer flies.
Mechanism: Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium *Francisella tularensis*. Here are the mechanisms and molecular details:

### Mechanism
Tularemia is primarily transmitted to humans via:
- Tick and deer fly bites
- Handling infected animals
- Inhalation of contaminated aerosols or agricultural dust
- Ingestion of contaminated water or food

Once inside the human body, *Francisella tularensis* primarily targets macrophages, which are key cells of the immune system.

### Molecular Mechanisms
1. **Entry and Intracellular Survival**:
- The bacteria enter macrophages through various receptors, including complement receptors and mannose receptors.
- Inside the macrophages, *F. tularensis* escapes from the phagosome (the vesicle that engulfs the bacterium) into the cytosol. This escape is facilitated by the Francisella Pathogenicity Island (FPI), a cluster of genes encoding a type VI secretion system (T6SS) which helps the bacteria breach the phagosomal membrane.

2. **Immune Evasion**:
- *F. tularensis* modulates the host immune response by interfering with signaling pathways. It downregulates pro-inflammatory responses, thus evading early immune detection.
- The bacterium also resists killing by oxidative and other stress mechanisms within the host cells.

3. **Replication**:
- Once in the cytosol, *F. tularensis* replicates efficiently.
- Key metabolic genes help the bacterium utilize host cell nutrients, such as amino acids and fatty acids, for growth.

4. **Spread**:
- After replication, *F. tularensis* can induce cell death in macrophages, often via apoptosis, allowing the bacteria to be released and infect neighboring cells.

Understanding these molecular mechanisms is crucial for developing effective treatments and preventive measures against tularemia.
Treatment: If infection occurs or is suspected, treatment is generally with the antibiotics streptomycin or gentamicin. Doxycycline was previously used. Gentamicin may be easier to obtain than streptomycin. There is also tentative evidence to support the use of quinolone antibiotics.
Compassionate Use Treatment: Tularemia, also known as rabbit fever or deer fly fever, is an infectious disease caused by the bacterium Francisella tularensis. While streptomycin and gentamicin are the antibiotics most commonly used for treatment, there are some compassionate use and off-label or experimental treatments worth noting:

1. **Fluoroquinolones (e.g., ciprofloxacin, levofloxacin):** These have been used off-label for tularemia treatment in cases where first-line treatments are not suitable or available. Both ciprofloxacin and levofloxacin have shown efficacy in treating tularemia, especially in mild to moderate cases.

2. **Doxycycline:** This is another off-label antibiotic that can be used, particularly in situations where aminoglycosides are contraindicated. It has been utilized for both treatment and prophylaxis.

3. **Chloramphenicol:** Although not a first-line treatment, chloramphenicol has been used in certain tularemia cases, particularly those involving central nervous system infections.

4. **Live attenuated vaccine (LVS):** While not available for general public use, there have been cases where this investigational vaccine has been used for high-risk individuals or during outbreaks for compassionate use.

These treatments are considered when the standard therapies are not appropriate due to drug resistance, allergies, or other contraindications. Additionally, ongoing research may provide more information on the efficacy and safety of these and other potential treatments for tularemia.
Lifestyle Recommendations: For tularemia, the following lifestyle recommendations can help prevent infection:

1. **Avoidance of Ticks and Insects**: Use insect repellent containing DEET, wear long sleeves and pants, and perform regular tick checks when spending time in areas where ticks are common.

2. **Protective Clothing**: Wear gloves and masks when handling sick or dead animals, especially wild animals, to prevent direct contact with infectious agents.

3. **Safe Drinking Water**: Do not drink untreated surface water or water from sources that may be contaminated.

4. **Food Safety**: Ensure that meat, particularly from wild game, is thoroughly cooked to an internal temperature that kills bacteria.

5. **Pest Control**: Implement measures to reduce exposure to rodents and other small animals that may carry tularemia, such as keeping living areas clean and storing food properly.

6. **Hygiene**: Wash hands thoroughly with soap and water after handling animals or being outdoors, especially before eating or touching the face.
Medication: Tularemia, also known as rabbit fever, is commonly treated with antibiotics. The most effective antibiotics include streptomycin and gentamicin. Doxycycline and ciprofloxacin can also be used as alternative treatments. The choice of antibiotic and duration of treatment depend on the form and severity of the disease. Treatment typically lasts for 10-21 days.
Repurposable Drugs: There is limited data on repurposable drugs for tularemia, a disease caused by the bacterium Francisella tularensis. Standard treatment typically involves antibiotics such as streptomycin, gentamicin, doxycycline, and ciprofloxacin.

For repurposed drugs, options are not well-established, but there is some interest in exploring the efficacy of fluoroquinolones and tetracyclines beyond their traditional use. However, these need further validation through clinical trials to confirm their effectiveness and safety for tularemia treatment.
Metabolites: Tularemia, also known as "rabbit fever," is a bacterial infection caused by Francisella tularensis. It is a serious infectious disease that primarily affects rodents, rabbits, and hares but can also infect humans. While the specific metabolites of F. tularensis have been studied for diagnostic and therapeutic purposes, the primary focus is on understanding the pathogenic mechanisms and immune responses.

In the context of tularemia, important metabolic activities include:

1. **Carbohydrate metabolism** - F. tularensis can utilize various carbohydrates for energy, growing in specific carbohydrate-rich media.
2. **Amino acid metabolism** - The bacterium can synthesize some amino acids and depends on the host for others.
3. **Lipid metabolism** - F. tularensis alters host lipid metabolism to survive and replicate within host cells.
4. **Iron acquisition** - The organism has mechanisms to acquire iron from the host, which is vital for its growth and survival.

Understanding these metabolic pathways is crucial for developing diagnostic tools and treatments. Scientists are researching metabolic biomarkers that may assist in detecting and monitoring the disease.
Nutraceuticals: Nutraceuticals have not been established as a standard treatment for tularemia. Management of tularemia typically involves the use of antibiotics such as streptomycin, gentamicin, doxycycline, or ciprofloxacin. Nutraceuticals might be considered for supporting overall health, but they should not replace conventional therapies. Always consult a healthcare professional for tularemia treatment.
Peptides: Tularemia, also known as "rabbit fever," is caused by the bacterium *Francisella tularensis*. Peptides could play a role in diagnostic or therapeutic applications for tularemia. Peptide-based vaccines and diagnostic tests are areas of ongoing research, aiming to exploit the immune response they can elicit.

Nanotechnology (nan) can enhance diagnostics and treatments for tularemia. Nanoparticles can be used to improve the delivery of antibiotics or vaccines, ensuring that they are more effective. Additionally, nanotechnology-based diagnostic tools can provide rapid and sensitive detection of *F. tularensis* in clinical samples.