Melioidosis and Diabetes: Increased Susceptibility and Outcomes

Introduction

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an infectious disease endemic to Southeast Asia and northern Australia. It has a broad spectrum of clinical presentations, ranging from localised skin infections to sepsis and pneumonia. The bacterium thrives in soil and water, making individuals with frequent contact with contaminated environments, such as farmers and construction workers, particularly susceptible.¹

The relationship between melioidosis and diabetes mellitus has garnered significant attention due to diabetes being a major risk factor for severe infection and poor outcomes. Globally, the rising prevalence of diabetes, coupled with the spread of melioidosis beyond endemic regions, has heightened the need for a better understanding and management of this co-infection.¹

In the context of global health, the intersection of melioidosis and diabetes presents unique challenges and opportunities for research, public health initiatives, and clinical management. This article explores the epidemiology, pathophysiology, clinical implications, and public health strategies related to melioidosis in persons with diabetes. Understanding these aspects is crucial for improving patient outcomes and reducing the burden of this neglected tropical disease.¹

Epidemiology

Global distribution 

Melioidosis is predominantly found in Southeast Asia and northern Australia, where Burkholderia pseudomallei is endemic. However, sporadic cases have been reported in other regions, including South Asia, the Middle East, Africa, and the Americas. The exact global burden is difficult to ascertain due to underreporting and misdiagnosis in non-endemic areas.²

Melioidosis rates in the diabetic population

Diabetes mellitus is a significant risk factor for melioidosis, with diabetic patients being several times more likely to develop the infection compared to non-diabetics. Studies have shown that diabetes increases the risk of melioidosis by compromising the immune response, particularly in poorly controlled diabetes. The incidence and prevalence of melioidosis among diabetic populations vary by region and are influenced by local diabetes prevalence rates.²

Demographic trends in affected populations

The demographics of melioidosis patients are influenced by environmental and occupational exposure to Burkholderia pseudomallei-contaminated soil and water. People assigned male at birth are more commonly affected, likely due to occupational exposure, while older age and underlying conditions, such as diabetes and chronic kidney disease, are significant risk factors. Occupational exposure plays a crucial role in endemic areas.²

Pathophysiology 

Overview of Burkholderia pseudomallei 

Burkholderia pseudomallei is a Gram-negative bacterium found in soil and water. It is known for its ability to survive for long periods in the environment, and its resistance to various harsh conditions, making it difficult to eradicate from contaminated areas. The bacterium can infect humans and animals through inhalation, ingestion, or skin inoculation, leading to a wide spectrum of clinical manifestations.^1,2 

Mechanism of Infection 

The pathogenesis of melioidosis involves several virulence factors that enable Burkholderia pseudomallei to invade host cells, evade immune responses, and cause systemic infection. These include:

• Adhesion and invasion. The bacterium adheres to and invades host cells, particularly macrophages, using surface structures and secretion systems
• Intracellular survival. Burkholderia pseudomallei can survive and replicate within host cells, allowing it to evade immune surveillance and antibiotics
• Toxin production. The bacterium produces toxins and exoenzymes that contribute to tissue damage and systemic spread^1,2 

Diabetes as a risk factor

Diabetes mellitus significantly increases the susceptibility to melioidosis through multiple mechanisms:

• Hyperglycaemia and diabetes-related immune dysregulation weaken the immune responses of the body
• Diabetes leads to endothelial dysfunction and impaired vascular integrity
• Burkholderia pseudomallei can utilise glucose and other nutrients available in high concentrations in tissues damaged by diabetes, promoting bacterial growth and dissemination^3,4

Impact of diabetes-related comorbidities on melioidosis outcomes

Diabetic patients with melioidosis often present more severe clinical manifestations and worse outcomes compared to non-diabetics. Diabetes-related comorbidities, such as chronic kidney disease, peripheral vascular disease, and peripheral neuropathy, further exacerbate these outcomes:

• Diabetics are more likely to develop severe forms of melioidosis, including sepsis and pneumonia
• Diabetic patients have higher mortality rates due to delayed diagnosis, treatment challenges, and underlying comorbidities
• Diabetes-related complications often result in longer hospital stays and increased healthcare costs^1,2,3

Clinical manifestations

Melioidosis can present with a wide range of clinical manifestations. Common presentations include:

• Acute pneumonia is the most common presentation, characterised by fever, cough, and respiratory distress 
• Septicemia can occur in severe cases, presenting with high fever, chills, hypotension, and signs of multi-organ dysfunction
• Localised ulcers, abscesses, or cellulitis, often following skin inoculation
• Burkholderia pseudomallei can cause the formation of abscesses in the liver, spleen, and prostate
• Osteomyelitis and septic arthritis may occur, particularly in individuals with pre-existing risk factors, such as diabetes^2,4,5

Variations in diabetic patients

Diabetic patients with melioidosis may exhibit variations in symptoms and severity compared to non-diabetics:

• To present with severe forms of melioidosis
• Diabetes-related neuropathy and vascular insufficiency may obscure typical clinical signs, leading to delayed diagnosis or atypical presentations
• Chronic melioidosis, characterised by recurrent infections, may be more common in diabetic patients due to impaired immune responses and difficulties in bacterial eradication^2,4,5

Diagnostic challenges 

Diagnosing melioidosis, particularly in diabetic patients, can be challenging due to several factors:

• Clinical manifestations can overlap with other infectious diseases, leading to diagnostic confusion
• A chest x-ray may reveal non-specific findings or mimic other respiratory infections, requiring a high index of suspicion for melioidosis
• Culturing Burkholderia pseudomallei from clinical specimens remains the gold standard, but can be time-consuming and may yield false-negative results 
• Diabetic patients may have concurrent infections or comorbidities, complicating diagnosis and management⁵

Treatment

The treatment of melioidosis involves prolonged antibiotic therapy. Commonly used antibiotics include:

• Ceftazidime or a carbapenem for initial intensive therapy
• Trimethoprim-sulfamethoxazole (TMP-SMX) is often used for long-term eradication therapy^6,7,8

Challenges in antibiotic therapy:

• Burkholderia pseudomallei exhibits intrinsic resistance to many antibiotics, necessitating susceptibility testing
• Treatment durations of 12-20 weeks, or longer, are often required, posing challenges for patient adherence and monitoring
• Relapse can occur in patients with underlying conditions such as diabetes^6,7

Public health implications

Preventing and controlling melioidosis in diabetic populations requires targeted strategies:

• Educate diabetic patients and healthcare providers about the risks of melioidosis, especially in endemic regions
• Promote hand hygiene, the use of protective footwear, and avoid exposure to soil and surface water
• Emphasize the importance of maintaining optimal glycaemic control to reduce susceptibility to infections^7,8

Future outlook for management and outcomes

The future outlook for melioidosis management in diabetic populations is optimistic but requires concerted efforts:

• Continued adoption of multidisciplinary approaches involving infectious disease specialists, endocrinologists, and public health officials
• Development of targeted therapies based on a better understanding of bacterial virulence factors and host immune responses
• Strengthening public health infrastructure, surveillance systems, and awareness programs to reduce the burden of melioidosis
• To increase collaboration between researchers, healthcare providers, and policymakers to address melioidosis comprehensively

Continued investment in research and public health efforts is essential to achieve these goals.⁸

Summary

Melioidosis poses a significant threat to diabetic populations worldwide. It is endemic in Southeast Asia and northern Australia, with diabetic patients at increased risk due to impaired immune responses and diabetes-related comorbidities. The pathophysiology enables the bacterium to evade immune surveillance and cause severe infections. Clinical manifestations range from acute pneumonia and septicemia to chronic and atypical presentations, which can be exacerbated in diabetic patients.

Effective management relies on early diagnosis and prolonged antibiotic therapy, tailored to address challenges such as antibiotic resistance. Multidisciplinary approaches involving infectious disease specialists, endocrinologists, and public health officials are essential for optimising outcomes.

Public health implications underscore the importance of surveillance, education, and preventive measures, including promoting glycaemic control and potential vaccine development. Research gaps persist in understanding pathogenesis, optimising treatment regimens, and developing rapid diagnostics and vaccines.

Looking ahead, continued collaboration and innovation in research, clinical practice, and public health are crucial for improving management strategies and reducing the burden of melioidosis in diabetic populations globally. By addressing these challenges, we can enhance patient care, reduce mortality, and mitigate the impact of this neglected tropical disease.