Melioidosis

Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei, a Gram-negative, motile, and soil-dwelling bacillus. It primarily affects humans and animals in tropical and subtropical regions, particularly in Southeast Asia and Northern Australia. Often referred to as the “great mimicker”, melioidosis presents with a wide range of clinical symptoms, making it difficult to diagnose. The infection can range from mild localised abscesses to severe septicaemia and is potentially fatal if not treated promptly.

Historical Background and Discovery

The disease was first described in 1911 by Alfred Whitmore and C. S. Krishnaswami in Rangoon (now Yangon, Myanmar), who observed it in morphine addicts. Initially termed Whitmore’s disease, it was later named melioidosis, derived from the Greek melis (distemper of asses) and eidos (resemblance), due to its similarity to glanders—a disease caused by Burkholderia mallei.
Since its discovery, melioidosis has emerged as a significant public health concern in tropical regions. Increased awareness and improved diagnostic facilities have revealed that it is more widespread than previously believed, with sporadic cases reported in India, China, the Americas, and Africa.

Causative Agent: Burkholderia pseudomallei

Burkholderia pseudomallei is a saprophytic bacterium found in moist soil, surface water, and rice paddies. It is highly resilient, capable of surviving in harsh environmental conditions for years. The organism is an aerobic, non-spore-forming, bipolar-staining bacillus, characterised by its distinctive “safety-pin” appearance under the microscope.
The bacterium is classified as a Category B bioterrorism agent by the U.S. Centers for Disease Control and Prevention (CDC) due to its environmental persistence, infection potential, and difficulty in eradication.

Epidemiology

Melioidosis is endemic in:

• Southeast Asia: Thailand, Malaysia, Singapore, Vietnam, and Myanmar.
• Northern Australia: Especially the Northern Territory and Queensland.
• South Asia: Increasing cases reported from India and Sri Lanka.
• Other regions: Sporadic cases in Africa, Central America, and the Middle East.

It is estimated that there are 165,000 cases annually worldwide, with about 89,000 deaths, according to a study published in Nature Microbiology (2016). Underreporting is common due to misdiagnosis and limited laboratory capacity in endemic regions.

Mode of Transmission

Infection occurs primarily through environmental exposure rather than human-to-human transmission. The major routes of transmission are:

• Percutaneous inoculation: Entry through cuts, abrasions, or wounds while working with contaminated soil or water (common among farmers).
• Inhalation: Inhalation of dust or aerosols during heavy rains, storms, or floods.
• Ingestion: Consumption of contaminated water.
• Rarely: Person-to-person or vertical transmission (from mother to child).

Occupational risk groups include agricultural workers, construction labourers, and military personnel operating in endemic areas.

Risk Factors

While anyone can contract melioidosis, certain groups are at higher risk due to compromised immunity or environmental exposure:

• Diabetes mellitus (the most significant predisposing factor).
• Chronic kidney or liver disease.
• Chronic lung disease.
• Excessive alcohol consumption.
• Immunosuppressive therapy or cancer.
• Advanced age.

Pathogenesis

After entering the body, B. pseudomallei invades host cells, particularly macrophages, where it multiplies and spreads. It can evade the immune system by forming intracellular colonies and biofilms, leading to persistent infection.
The incubation period varies from 1 day to several years, depending on the route of entry and immune status. The bacterium’s ability to cause both acute and latent infections contributes to its reputation as a “time bomb” infection.

Clinical Manifestations

Melioidosis is known for its diverse clinical presentations, often resembling other diseases such as tuberculosis, pneumonia, or sepsis. The main forms include:

1. Localized Infection:
   • Abscesses or ulcers at the site of inoculation.
   • Fever and regional lymphadenopathy.
2. Pulmonary Infection:
   • The most common presentation.
   • Ranges from mild bronchitis to severe pneumonia.
   • Symptoms: Cough, chest pain, fever, and abscess formation.
3. Septicaemic Melioidosis (Sepsis):
   • Rapidly progressive and often fatal if untreated.
   • Features: High fever, hypotension, multi-organ failure, and abscesses in the liver, spleen, or kidneys.
4. Chronic Melioidosis:
   • Mimics tuberculosis with prolonged fever, weight loss, and lung nodules.
   • May persist for years with intermittent relapse.
5. Latent Infection:
   • The bacterium may remain dormant and reactivate after decades, especially during immune suppression (similar to Mycobacterium tuberculosis).

Diagnosis

Diagnosis of melioidosis requires a high index of suspicion, especially in endemic regions. Common diagnostic methods include:

• Microbiological Culture: Isolation of B. pseudomallei from blood, pus, urine, or sputum on Ashdown’s agar is the gold standard.
• Gram Staining: Reveals characteristic bipolar (“safety-pin”) appearance.
• Serological Tests: Indirect haemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA).
• Molecular Methods: Polymerase chain reaction (PCR) for rapid detection.
• Imaging: Ultrasound or CT scan to detect internal abscesses.

However, due to its similarity to other Gram-negative bacteria, misidentification remains common in resource-limited settings.

Treatment

Effective management of melioidosis requires prolonged antibiotic therapy divided into two phases:

1. Intensive Phase (Initial Treatment):
   • Intravenous (IV) antibiotics for 10–14 days or longer:
     • Ceftazidime (preferred).
     • Meropenem or Imipenem in severe cases.
2. Eradication Phase (Follow-up Treatment):
   • Oral therapy for 3–6 months to prevent relapse:
     • Trimethoprim-sulfamethoxazole (TMP-SMX) ± Doxycycline.

Supportive care for septic shock and organ dysfunction is essential. Relapse is common if the treatment course is incomplete.

Prevention and Control

Currently, there is no licensed vaccine for melioidosis. Preventive measures focus on reducing exposure and improving public awareness:

• Use protective clothing and gloves while handling soil or water.
• Avoid direct contact with stagnant water during floods or monsoons.
• Ensure safe drinking water.
• Control diabetes and other chronic diseases to reduce susceptibility.
• Strengthen diagnostic facilities in endemic areas.

For laboratory workers, strict biosafety level 3 (BSL-3) precautions are necessary when handling B. pseudomallei.

Epidemiological Situation in India

Melioidosis has emerged as an underdiagnosed infection in India, with cases reported from Kerala, Tamil Nadu, Karnataka, Maharashtra, and northeastern states. The Kozhikode and Mangaluru regions in South India are considered endemic. Improved diagnostic awareness has led to increasing detection, particularly among diabetic patients and agricultural workers.

Global and Public Health Importance

Melioidosis poses a serious public health threat due to its high mortality (30–50% in untreated cases), potential for outbreaks after natural disasters, and misdiagnosis as tuberculosis or sepsis. Climate change and increased flooding are expected to expand its geographic range.

Research and Future Directions

Research is ongoing in areas such as:

• Development of vaccines targeting virulence factors of B. pseudomallei.
• Rapid diagnostic kits for use in endemic rural areas.
• Surveillance programmes integrating melioidosis into national infectious disease registries.