Melioidosis

Introduction

Melioidosis refers to a spectrum of diseases caused by Burkholderia pseudomallei. The disease may present with recurrent or prolonged pyrexia with or without lymphadenitis, pyogenic abscesses of the skin, subcutaneous tissue, liver, spleen, or brain, osteomyelitis, pneumonia or septicemia.

A heither-to-undescribed microorganism was first detected and described in 1912 by an Indian Bacteriologist C.S. Krishnaswami while working with Capt. A. Whitmore, a British Physician at Rangoon General Hospital, Burma (now called Myanmar).¹ The organism was included in the genus Bacillus for many years and later shifted to the genus Pseudomonas. The inclusion was due to the similarities in the morphologic characteristics, biochemical properties and culture, with species of Pseudomonas. It was called Pseudomonas pseudomallei for a long time. Stanton and Fletcher labeled the disease state as Melioidosis in 1932.² The term means ‘a similarity to distemper of asses’.

In 1992, the organism was assigned to a newly named genus Berkholderia.³ The name was given in honor of the American plant Pathologist, Walter Burkholder who described a particular species of this group following an outbreak of infection in onion growers in New York State in 1949, which turned out to be another species included in this genus. The causative agent was later called Burkholdaeria cepacia (Latin for ‘like onion’).

Epidemiology

Melioidosis is endemic in Far East, Southeast Asia, Northern Australia and India. Meliodosis forms the most common cause of septicemia in Northern Thailand. The initial report of existence of melioidosis in India was recorded in foreigners who visited India. Ives and Thompson reported the first case in 1953 from Scotland who got infected in Central India where he was working as a mining engineer.⁴ The second report came from Germany after 35 years, of a septic melioidosis following a visit to India.⁵ In both cases, the travelers had contacted the disease in India and the disease was manifested after return to their homeland.

In 1991, Raghavan and colleagues reported the first case of melioidosis in a child in Mumbai.⁶ Since then melioidosis has been reported in different parts of the country including Kerala, Maharashtra, Karnataka, Tamil Nadu, Pondicherry, Andhra Pradesh, Odisha, West Bengal, Assam and Tripura. The 1994 outbreaks of plague-like illness in the form of bubonic plague in Beed, Maharashtra, and pneumonic plague in Surat, Gujarat put the microbiologists on guard to find out alternate aetiologies for conditions simulating plague and it resulted in the detection of widespread prevalence of melioidosis in different parts of India.^7,8 Increasing number of cases of melioidosis have been recognized in India in the recent decade.⁹ It has been observed that more than 90% of reported cases (nearly 1,500 out of 1,700) from India have occurred during last 10 years. In US, several cases of melioidosis were reported following use of aroma spray of lavender and chamomile imported from India, implying transmission of B pseudomallei through commercial liquid agents.¹⁰

B pseudomallei is found as a saprophyte in the soil and water (paddy fields). The infection may be acquired either through abrasion, or penetrating wound in the skin, or by inhalation or ingestion.

Many American soldiers were infected during invasion of Viet Nam. They manifested pulmonary or other forms of melioidosis following their return to their homeland. Lung disease was commonly observed in helicopterborne soldiers. Inhalation of dust raised by landing helicopters appeared to be the reason for the disease and the condition had been nicknamed as ‘Vietnam tuberculosis’. Many other soldiers who fought in Viet Nam, developed different forms of melioidosis many years after return to US. It was given the name ‘Viet Nam time bomb’.¹¹

Aetiolopathology

B pseudomallei is a motile, aerobic, Gram-negative bacillus, often mistaken for Pseudomonas species. The incubation period is not clear. It may be as short as two days or can be clinically unapparent by remaining latent for many years. The infection remains latent for a prolonged period and later may present features mimicking tuberculosis. Histopathologic examination of the lesions may show granuloma and necrosis. Though it may be mistaken for tuberculous lesion, it lacks presence of acid-fast bacteria. Yersinia pestis, causative organism of plague and pseudomallei share the properties of bipolar staining, giving a ‘safety pin’ appearance in Gram-stained smears.¹² B pseudomallei grows in filamentous chains and staining with methylene blue or Wright’s stain shows bipolar ‘safety pin’ pattern.

The pathogenesis of melioidosis is not fully established. The condition mimics pyogenic bacterial infections, gram-negative septicemia, or tuberculosis. A bacteraemia is followed by development of abscess (es) in many organs. The manifestations depend on the size of inoculums, route of infection, virulence of infecting strain and the host’s immune system. The organism may also develop as an opportunistic pathogen. The infection may remain latent for prolonged period and later manifest with features simulating tuberculosis. The infection develops as a primary pathogen in many subjects with good health.

Many underlying diseases such as diabetes mellitus, alcoholism, chronic renal failure, cirrhosis of the liver and severe burns appear to predispose the activation of dormant infection.

Clinical features

Melioidosis presents with a wide variety of clinical features as a ‘remarkable imitator’ of many diseases.¹³ The condition may present with acute or chronic manifestations or it may remain as a subclinical or latent infection.

The infection with B pseudomallei may remain mild without any symptoms. The individual remains as a chronic carrier. Probably the robust immune system of the individual prevents the development of the disease. The condition may remain latent for many years and later becomes clinically apparent. There can be relapse of the condition during suppressed immune state.

The common presentations are in the form of septicemia, suppuration or acute pulmonary infection. Chronic presentation occurs in the form of suppurative condition.

Septic syndrome

After a short history of exposure to the infection, the patient presents with high fever with rigors. Many exhibit marked weight loss. The primary focus of infection may be in the skin, subcutaneous tissue or lung. In those with bacteraemia complicating pneumonia, there is severe degree of dyspnoea, severe pustular skin lesions, and deterioration of general condition. Patient may exhibit jaundice, diarrhoea, confusion and stupor. Most are profoundly ill. Clinical examination shows marked muscle tenderness. There may be mild hepatosplenomegaly and signs of arthritis or meningitis. Lung may not reveal any abnormal signs except some crackles. Many patients succumb to septic shock. Bilateral patchy infiltrates seen in the chest radiograph may progress to abscess or cavitation if the patient survives.

Acute localized suppuration

Entry of B pseudomallei through an abrasion in the skin results in a nodular swelling with acute lymphangitis and regional lymphadenopathy. The condition may progress to acute septic syndrome.

Acute pulmonary infection

Pulmonary infection forms one of the commonest form of presentation of the disease. Lungs may become the seat of the disease following primary infection or after a haematogenous dissemination of sepsis. The condition may begin suddenly without any prodromal features or gradually with fever, headache, and loss of appetite. The patient complains of generalized muscle ache. There may be cough, expectoration, hemoptysis and marked weight loss. Radiologic examination of the chest shows presence of nodular infiltration or thin-walled cavities with a predilection to the upper lobes. However, the cavitation may affect any lobe. The condition may lead to complications such as pneumothorax, emphysema and septicemia.

Chronic suppuration

Some patients may present with abscesses involving many organs such as lung, liver, spleen, bones, lymph nodes, brain and skin.

Pulmonary mass lesion

The infection may present as a mass lesion in chronic smokers which may require Endobronchial Ultrasound (EBUS) guide sheath technique to locate the lesion and culture bronchial brushings.¹⁴

Investigations

Hematologic examination reveals leucocytosis, and raised levels of C-reactive protein. Bipolar- or irregular staining Gram-negative rods may be demonstrable in the microscopic examination of the sputum, or pus. The culture of blood, sputum or pus gives a sweet smell of putrefaction in initial stages of culture and later colonies give a wrinkled appearance. The colonies resemble a cream to orange colour flower with folds radiating from a central core. Specific B pseudomallei antibodies are demonstrable by hemagglutination, direct agglutination and complement-fixing antibody tests. Enzyme-linked immunosorbent assay (ELISA) is helpful in detecting IgG.¹⁵

Pulmonary melioidosis needs to be considered in differential diagnosis of any febrile illness in patients coming from endemic regions if they have diabetes mellitus and give a history of exposure to contaminated soil and exhibit rapidly progressive pneumonia or cavitary lung disease.¹⁶

Prognosis

Pulmonary or septic disease has a very high mortality rate. They are to be treated aggressively with ceftazidine when suspected. Those with septicemia are often gravely ill and show a high mortality. Prognosis for the patients with localized disease is excellent with appropriate therapy. The infection has the ability to remain dormant with recrudescence, like tuberculosis, occurring many years following the initial infection.

Treatment

B pseudomallei is resistant to aminoglycosides, penicillin and cephalosporins. Anti-tuberculosis drugs when administered on a mistaken diagnosis of tuberculosis do not show any response. Melioidosis is treated with ceftazidime, a third-generation cephalosporin, at a dose of 120 mg/kg a day in divided doses. Ceftazidime may be administered intraveneously in the initial 2-4 weeks to be followed by oral therapy for six months or longer to prevent recrudescence. Instead, in the follow-up period, doxycycline may be administered at a daily dose of 200 mg for 2-3 months to prevent relapse. Tetracyclines, amoxicillin-clavulanic acid, and /or trimethoprim-sulphamethoxazole are also useful in the later part of the treatment to reduce relapses with its associated mortality. The abscesses should be drained surgically.

The sporadic reports of melioidosis from different parts of India have drawn the attention of its endemicity. The condition can present in many guises such as prolonged fever, abscess, pneumonia, osteomyelitis, tuberculosis, plague, septicemia or multi-organ failure. Many a times the diagnosis of melioidosis is missed and treated with a variety of antibiotics to most of which it is resistant.

As the organism is found in the soil as a saprophyte, many villagers involved in agriculture are exposed and are prone to infection with B pseudomallei. This condition must be included in the differential diagnosis and the physician must be aware of this neglected killer disease. As Jacob John stated, the disease becomes killer only if not diagnosed and treated correctly.⁸

Conflict of Interest

None