Melioidosis

Melioidosis, also known as pseudoglanders and Whitmore's disease (after Capt Alfred Whitmore) is an uncommon infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei, found in soil and water. It exists in acute and chronic forms.

The causative organism, Burkholderia pseudomallei, was thought to be a member of the Pseudomonas genus and was previously known as Pseudomonas pseudomallei. This organism is phylogenetically related closely to Burkholderia mallei, the organism that causes glanders. Another closely-related but less virulent bacterium is found in soil in Thailand and is called Burkholderia thailandensis.

Melioidosis is endemic in parts of south east Asia (including Thailand, Singapore, Malaysia, Burma and Vietnam) and northern Australia. Multiple cases have also been described in southern China and Hong Kong, Brunei, Taiwan, India and Laos, and sporadic cases in Central and South America, the Middle East, the Pacific and several African countries. An outbreak at the Paris Zoo in the 1970s ("l’affaire du jardin des plantes") was thought that have resulted from imported animals.

Up to 30% of adults in some endemic areas may test positive for antibodies against B. pseudomallei (depending on the population and test). It affects humans as well as other animals such as goats, sheep, horses and cattle. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. The mode of infection is believed to be either through a break in the skin, or through the inhalation of aerosolized B. pseudomallei.

There has also been increasing interest in melioidosis because it has the potential to be developed as a biological weapon. It is classed by the US Centers for Disease Control (CDC) as a category B agent.

Symptoms and signs

The incubation period can range from 2 days to several decades, but the median incubation period of acute melioidosis is 9 days. Patients with latent melioidosis may be symptom free for decades; the longest duration between presumed exposure and clinical presentation is 62 years. There is a wide spectrum of severity; in chronic presentations, symptoms may last months, but fulminant infection may present with severe symptoms over hours.

A patient with active melioidosis usually presents with fever. There may be pains in multiple sites around his/her body due to bacteremia and abscess formation. Patients with melioidosis usually have risk factors for disease, such as diabetes, thalassemia, hazardous alcohol use or renal disease. However, otherwise healthy patients, including children, may also get melioidosis.

If there is pulmonary involvement, there may be signs and symptoms of pneumonia.

If hepatic or splenic abscesses are present, the patient may present with abdominal pain. If there are brain abscesses present, the patient may present with neurological signs and symptoms. An encephalomyelitis syndrome is recognised in northern Australia.

Melioidosis may also cause osteomyelitis and present with bony pain. In Thailand, parotid abscesses in children are common.Other sites of infection include the urinary tract (with prostatic abscesses common in Australia), skin and soft tissue abscesses. Less common manifestation include intravascular infection, lymph node abscesses, pyopericardium and myocarditis, mediastinal infection, and thyroid and scrotal abscesses and ocular infection.

Diagnosis

A definite history of contact with soil may not be elicited as melioidosis can be dormant for many years before becoming acute. Attention should be paid to a history of travel to endemic areas in returned travellers. Patients with diabetes mellitus often have a more serious presentation of melioidosis. Some authors recommend considering possibility of melioidosis in every febrile patient with a history of traveling to and/or staying at endemic areas.

The Differential diagnosis is extensive; melioidosis may mimic many other infections, including tuberculosis.

A definitive diagnosis can be made by growing B. pseudomallei from any site, including blood cultures, pus aspirated from an abscess, sputum or urine cultures. A throat swab is not sensitive but is 100% specific if positive. Ashdown's medium, containing gentamicin, may be required for cultures from non-sterile sites. Burkholderia cepacia medium may be a useful alternative selective medium in non-endemic areas.

There is also a serological test for melioidosis, but this is not commercially available in most countries. A high background titre may reduce the positive predictive value of serology in endemic countries.

If clinically indicated, CT scans (or, in some cases, ultrasound scans) of the thorax and abdomen are useful to investigate for the presence of abscesses and to rule out other diseases.

Treatment

Intravenous ceftazidime is the drug of choice for treatment of acute melioidosis. Intravenous amoxicillin-clavulanate (co-amoxiclav), meropenem or imipenem are also active. Intravenous antibiotics should be given for at least 10-14 days. Following the treatment of the acute disease, it is recommended that oral antibiotics such as co-trimoxazole be used for three to six months to clear the organism from the body, so as to prevent a recurrence. A clinical trial has established that the combination of cotrimoxazole and doxycycline is as effective as, and better tolerated than, the combination of cotrimoxazole, doxycycline and chloramphenicol.

Prognosis

Before the era of modern antibiotics, the septicemic form of melioidosis had a high mortality rate exceeding 90%. With modern antibiotics, the mortality rate is about 10% for uncomplicated cases but up to 80% for cases with severe sepsis. It seems certain that access to intensive care facilities is also important, and probably explains why total mortality is 20% in Northern Australia but 40% in Northeast Thailand.

Recurrence may occur in 10-20% of patients. Risk factors include poor compliance with eradication therapy and duration of eradication therapy less than 8 weeks. Molecular studies have established that the majority of recurrences are due to the original infecting strain, but a significant proportion of recurrences in endemic areas may be due to reinfection, particularly after 2 years.

Prevention

There are only few cases documented for person-to-person transmission; no isolation is required for patients with melioidosis. Lab workers should handle Burkholderia pseudomallei under PC3 isolation conditions, as laboratory acquired melioidosis has been described.

In endemic areas, people (rice-paddy farmers in particular) are warned to avoid contact with soil, mud and surface water where possible. Case clusters have been described following flooding and cyclones and probably relate to exposure. Other case clusters have related to contamination of drinking water supplies. Populations at risk include patients with diabetes mellitus, chronic renal failure, chronic lung disease or patients with an immune deficiency of any kind. The effectiveness of measures to reduce exposure to the causative organism have not been established. A vaccine is not yet available.

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Infectious diseases