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Melioidosis

Disease Details

Family Health Simplified

Description
Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, typically found in soil and water in tropical and subtropical regions.
Type
Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. It is not a genetically transmitted disease; it is acquired through environmental exposure, typically through direct contact with contaminated soil or water. There is no genetic transmission associated with melioidosis.
Signs And Symptoms
Melioidosis, caused by the bacterium Burkholderia pseudomallei, can present with a wide range of signs and symptoms. These can vary depending on the route of infection and the organs involved. Common signs and symptoms include:

1. **General Symptoms**
- Fever
- Weight loss
- Muscle or joint pain
- Headache

2. **Pulmonary Melioidosis**
- Cough (with or without mucus)
- Chest pain
- Breathing difficulties

3. **Localised Infection**
- Pain or swelling at the site of the infection
- Abscess formation

4. **Bloodstream Infection (Septicemia)**
- Fever
- Confusion
- Respiratory distress

5. **Chronic Melioidosis**
- Chronic cough
- Chest pain
- Fever
- Weight loss

The symptoms can vary greatly and mimic other diseases, making diagnosis challenging.
Prognosis
In well-resourced settings, where the disease can be detected and treated early, the risk of death is 10%. In resource-poor settings, the risk of death from the disease is more than 40%.Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of B. pseudomallei bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur.
Onset
Melioidosis typically has an incubation period ranging from a few days to several weeks after exposure to the bacterium *Burkholderia pseudomallei*. The onset of symptoms can be acute, with rapid development of fever, pneumonia, and sepsis, or chronic, with symptoms developing gradually over weeks to months, including weight loss, fever, and abscess formation in various tissues.
Prevalence
Melioidosis is an infectious disease caused by the bacterium *Burkholderia pseudomallei*. It is most commonly found in tropical and subtropical regions, notably Southeast Asia and northern Australia. The prevalence of melioidosis can vary significantly by region, but in hyperendemic areas like northeast Thailand and northern Australia, it can be a substantial public health concern. Cases are reported less frequently from other parts of Asia, South America, and the Caribbean. The disease can manifest in both humans and animals, contributing to its spread and persistence in endemic areas.
Epidemiology
Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. In approximately half of those cases (54% or 89,000), people will die. Under-reporting is a common problem as only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on the modelling. Lack of laboratory diagnostic capabilities and lack of disease awareness amongst health care providers also causes under diagnosis. Even if bacterial cultures show positive result for B. pesudomallei, they can be discarded as contaminants especially in laboratories in non-endemic areas. In 2015, it was estimated that the yearly disability-adjusted life year (DALY) was 84.3 per 100,000 people. As of 2022, melioidosis is not included in the WHO list of neglected tropical diseases.
Intractability
Melioidosis, caused by the bacterium *Burkholderia pseudomallei*, can be challenging to treat due to its varied clinical presentations and potential for high mortality. However, it is not considered intractable as it can be managed with appropriate antibiotic therapy. Treatment typically involves an intensive phase with intravenous antibiotics like ceftazidime or meropenem for 10-14 days, followed by an eradication phase with oral antibiotics such as trimethoprim-sulfamethoxazole for 3-6 months. Early diagnosis and consistent treatment are crucial for effective management.
Disease Severity
Melioidosis can range from mild to severe depending on the infection site and the patient’s health status. It can cause localized, acute, subacute, or chronic infections and, if untreated, it may lead to severe complications or even death. The severity is largely contingent on early diagnosis and prompt treatment.
Healthcare Professionals
Disease Ontology ID - DOID:5052
Pathophysiology
Melioidosis is caused by the bacterium Burkholderia pseudomallei. The pathophysiology involves the bacteria gaining entry into the body through inhalation, ingestion, or skin abrasions. Once inside, B. pseudomallei evades the host's immune system and can survive and replicate within phagocytes, leading to granuloma formation in tissues. The bacteria can infect multiple organ systems, leading to a wide range of clinical manifestations, from localized infections to severe disseminated disease and septicemia. Key pathological processes include acute inflammation, abscess formation, and extensive tissue necrosis.
Carrier Status
Melioidosis is an infectious disease caused by the bacterium *Burkholderia pseudomallei*. There is no known carrier status for melioidosis; infection typically occurs through direct contact with contaminated soil or water. The disease is not considered contagious between humans under normal circumstances.
Mechanism
Melioidosis is primarily caused by the Gram-negative bacterium Burkholderia pseudomallei.

### Mechanism:
1. **Transmission**: Human infection typically occurs through direct contact with contaminated soil or water, often via skin abrasions, inhalation, or ingestion.
2. **Colonization and Invasion**: Upon entry, B. pseudomallei can adhere to and invade epithelial cells and macrophages, rapidly spreading through the bloodstream to various organs.

### Molecular Mechanisms:
1. **Virulence Factors**:
- **Type III and Type VI Secretion Systems (T3SS and T6SS)**: These systems inject effector proteins into host cells, which manipulate host cell processes to the bacteria's advantage, aiding in invasion and immune evasion.
- **Quorum Sensing**: A regulatory system that coordinates the expression of virulence genes based on bacterial population density, enhancing pathogenicity.
- **LPS (Lipopolysaccharides)**: The bacterial outer membrane component triggers strong immune responses but can be modified to resist host immune defenses.

2. **Intracellular Survival**:
- **Actin-Based Motility**: B. pseudomallei utilizes actin polymerization to move within and between cells, evading immune detection.
- **Phagosomal Escape**: After being phagocytosed by macrophages, the bacteria can escape from phagosomes into the cytoplasm, avoiding degradation.

3. **Immune Evasion**:
- **Antioxidant Enzymes**: Production of enzymes like catalases and superoxide dismutases help neutralize reactive oxygen species generated by the host's immune cells.
- **Biofilm Formation**: Facilitates chronic infection and resistance to antimicrobial agents.

Understanding these mechanisms is crucial for developing effective treatments and preventive measures against melioidosis.
Treatment
The treatment of melioidosis is divided into two stages: an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various antibiotics. B. pesudomallei are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs generally kill bacteria. B. pseudomallei is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs generally inhibit the growth of the bacteria. However, the bacteria are resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins. On the other hand, 86% of the B. pseudomallei isolates from the region of Sarawak, Malaysia are susceptible to gentamicin and this has not been found elsewhere in other parts of the world.Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer used unless no other alternatives are available. All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline.
Compassionate Use Treatment
For melioidosis, compassionate use treatments and off-label or experimental treatments may include:

1. **Ceftazidime**: Typically the primary treatment, but also used under compassionate conditions if standard treatments are unavailable.
2. **Meropenem**: An alternative to ceftazidime, often considered for severe cases or when resistance is noted.
3. **Cotrimoxazole (Trimethoprim/Sulfamethoxazole)**: Sometimes used off-label in combination with other antibiotics for prolonged therapy.
4. **Combination therapy**: Using a combination of antibiotics (e.g., ceftazidime and cotrimoxazole) might be considered experimental but has been employed in certain resistant or severe cases.
5. **Tigecycline and Eravacycline**: These newer antibiotics have been explored in experimental settings for their efficacy against Burkholderia pseudomallei, the bacteria responsible for melioidosis.

Patients treated under these protocols need careful monitoring due to the potential for severe side effects and the critical nature of the disease.
Lifestyle Recommendations
For melioidosis, lifestyle recommendations focus on reducing exposure and managing health:

1. **Avoiding Exposure:**
- Stay away from soil and standing water in endemic areas, particularly during the rainy season.
- Wear protective clothing, such as gloves and boots, when handling soil, muddy water, or working in agriculture.

2. **Personal Hygiene:**
- Wash hands regularly with soap and water, especially after soil contact.
- Clean and cover skin wounds immediately to prevent infection.

3. **Protecting High-Risk Individuals:**
- People with chronic conditions like diabetes, kidney disease, or weakened immune systems should be extra cautious.

4. **Travel Precautions:**
- Travelers to endemic areas should take preventive measures to avoid exposure to contaminated soil and water.

5. **Educating Others:**
- Raise awareness about melioidosis in at-risk communities to encourage preventive behaviors.
Medication
The primary medication used to treat melioidosis is antibiotics. The initial phase typically involves intravenous antibiotics such as ceftazidime or meropenem for at least 10-14 days, followed by an eradication phase with oral antibiotics like trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months to prevent relapse. Treatment plans can vary based on the severity of the disease and patient response.
Repurposable Drugs
Repurposable drugs for melioidosis include **ceftazidime**, **meropenem**, **imipenem**, **trimethoprim-sulfamethoxazole**, **doxycycline**, and **amoxicillin-clavulanate**. These antibiotics have shown efficacy in treating Burkholderia pseudomallei infections, the bacterium responsible for melioidosis.
Metabolites
For melioidosis, specific information about metabolites may vary depending on the context of the disease and its study. However, a notable metabolite related to the pathogen Burkholderia pseudomallei, which causes melioidosis, is the siderophore known as malleobactin. Siderophores are molecules that bind and transport iron, which is essential for the bacterial growth and virulence. Malleobactin helps Burkholderia pseudomallei to obtain iron from its environment, contributing to its ability to cause infection.

The term "nan" suggests that there might be non-availability of certain data related to specific metabolites under different conditions or stages of infection. If you need precise profiling of metabolites during melioidosis, it typically requires advanced analytical techniques such as mass spectrometry or NMR spectroscopy applied to clinical or laboratory samples.
Nutraceuticals
There is currently no clear evidence supporting the use of nutraceuticals in the treatment or prevention of melioidosis. Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, typically treated with specific antibiotics such as ceftazidime, meropenem, or trimethoprim-sulfamethoxazole. Always consult healthcare professionals for proper diagnosis and treatment.
Peptides
Melioidosis is caused by the bacterium Burkholderia pseudomallei. Peptides play a role in the immune response to this infection; for instance, antimicrobial peptides like defensins help combat the bacterial infection. Additionally, synthetic peptides are being studied for their potential in vaccine development against melioidosis.

Nanotechnology is being researched for its potential in diagnosing and treating melioidosis. Nanoparticles can enhance drug delivery, improving the efficacy of antibiotics and potentially reducing side effects. Nanotechnology also offers advanced diagnostic tools, enabling more rapid and sensitive detection of Burkholderia pseudomallei.