Burkholderia pseudomallei group

BURKHOLDERIA PSEUDOMALLEI GROUP^ref

Burkholderia pseudomallei (a.k.a. Pseudomonas pseudomallei, Whitmore's bacillus)

Burkholderia pseudomallei (Ara⁺ biotype)

Burkholderia thailandensis (much less virulent. Formerly considered to be a separate biotype, these L-arabinoside assimilators account for about 25% of soil isolates in Thailand (M5)^ref)

Table of contents :

Epidemiology

Transmission

Symptoms & signs

Laboratory examinations

Therapy

Prognosis

Prevention

Epidemiology : first described in Rangoon, Burma (now Myanmar) by Whitmore and Krishnaswami in 1912 among homeless, debilitated morphine addicts. Most documented cases occur in the tropical north of Australia (38 melioidosis cases (11 deaths) in North Queensland^ref in 2000, 8 cases in 2001, 23 in 2002, and 8 in 2003^ref), South and Central America, and the Middle East (particularly relevant here)^ref. Cases were subsequently described with isolation of the organism from clinical specimens and soil from many countries primarily in eastern Asia. The infection was recognized in both Allied and Japanese soldiers during the Second World War and subsequently was recognized in Northern Australia, possibly introduced there by returning troops. Anyway it is unlikely that melioidosis was introduced by returning Australian soldiers following WW2. There is extensive molecular diversity of isolates throughout northern Australia, including many isolated coastal islands with little external contact^ref. Introduction of melioidosis is believed to have occurred to areas outside the endemic area such as a focus in southwest West Australia, where clinical isolates over 25 years were clonal on ribotyping^ref. Later, during the Vietnamese war of independence with France and, more so, the USA involvement, there were many more cases described. Because of the infection's potential to produce potentially life-threatening reactivations several decades after exposure, the term "Vietnam time bomb" was used. It is likely that many of the acute and fatal cases in troops remained undiagnosed. Also a disease of animals (endemic and enzootic to Ovis aries , Capra hircus , Sus scrofa , Equus caballus , Bos taurus , Rodentia and Aves spp. in Southeast Asia), melioidosis is not truly a zoonosis, since it is not transmitted from animals to man but rather both acquire the infection from its soil reservoir. It may cause infection in many species and has become a significant veterinary pathogen in zoological gardens. As pointed out by White, the infamous L'affaire du Jardin des Plantes was said to have occurred after a panda donated in 1973 by Mao Tse-Tung to the French president Pompidou was the index case of melioidosis that significantly affected several French zoos as well as race and equestrian horses. The disease is endemic in South East Asia and as noted above more recently in Northern Australia^ref, but cases have been described in the western hemisphere without travel histories as well. Only a few cases have been reported in South America^ref and Africa^ref. In the islands of the southwest Indian Ocean, although no human cases have been reported, B. pseudomallei has been isolated from pigs in Madagascar as far back as 1936 (Girard G. Le porc peut-il etre un porteur sain de bacille de Whitmore? Bull Soc Pathol Exot. 1936;29:712-6) and from the soil in Madagascar and La Reunion^ref. The 1st case of human melioidosis in the southwest Indian Ocean island of Mauritius was a 40-year-old housewife with systemic lupus erythematosus (SLE) living in Cite La Cure, a poor suburb of the capital city Port-Louis admitted to the hospital on 29 Jan 2004. She had never traveled abroad. According to her mother, her home becomes very muddy after heavy rainfall, and her feet were often in mud while performing her household duties. Veterinary cases do not appear to have been reported previously in Mauritius. Before 1998, oxidase-positive gram-negative bacilli other than P. aeruginosa were not identified to species level in laboratories in Mauritius. Since then, such organisms are routinely identified by API 20NE when isolated in pure culture from blood, but only occasionally when isolated from nonsterile sites such as sputum and pus swabs. Thus, nonsepticemic cases of melioidosis in Mauritius could easily have been missed. An association between rainfall and melioidosis has long been recognized; most cases in Thailand^ref and northern Australia^ref occur during the wet season. The increased number of cases noted during the rainy season may be caused by the movement of B. pseudomallei from deeper layers toward the surface when dry topsoil is moistened by rainfall^ref. In Mauritius, the rainy season is December to March. In January 2004, 196 mm rainfall was recorded in Port-Louis, which is 37% higher than the 1971-2000 mean rainfall for the region during this month. January 2004 was the 6th wettest January of the past 30 years in Port-Louis. Similarly, above-average rainfall was recorded throughout the island in 2004^ref. Those most at risk are immunosuppressed groups, including conditions such as diabetes mellitus (commonest risk factor), renal disease, cirrhosis, thalassemia, alcohol dependence, cancer, immunosuppressive therapy, chronic obstructive lung disease, cystic fibrosis, and excess kava consumption (kava is an herbal member of the pepper family that can be associated with chronic liver disease). Melioidosis may present at any age, but peaks in the 4th and 5th decades of life, affecting men more than women. In addition, although severe fulminating infection can and does occur in healthy individuals, severe disease and fatalities are much less common in those without risk factors. It has occasionally been acquired in Fiji
Transmission : an environmental saprophyte living in soil and surface water in endemic areas, particularly in rice paddies, in mud and damp soil, enters the body through ...

inoculation through a break in the skin (cuts and sores)
ingestion of contaminated water. This is a hard-core survivalist organism that can persist in triple-distilled water for long periods of time
inhalation of dust droplets (after aerosolization of soil or water)
nasal instillation
very rarely from person to person

2 outbreaks in Australia have also implicated potable water supplies rather than surface water as a potential source of the infection. It a wet-season disease and cases commonly increased after heavy rain and flooding. The association between rainfall and cases is well-described, with a shift in the presentation of disease to pneumonia and more severe disease after heavy rain^ref. Clustering has also been noted after other severe weather events such as the Katherine floods in Jan 1998 and heavy rainfall after tropical cyclone Thelma in Dec 1998. The organism may exist in a viable, non-cultivable state in the environment, interacting with other organisms, particularly protozoa, which might explain its adaptation to an intracellular niche
=> asymptomatic
=> melioidosis / rodent glanders / Whitmore's fever / Nightcliff gardeners' disease (the term melioidosis as related by White was coined by Fletcher and Stanton from Kuala Lumpur, Malaysia from the Greek words melis (a distemper of asses) and eidos (resemblance)) after 2 days-some years incubation : high fever

, significant muscle aches, chest pain and -- although the cough

can be nonproductive -- respiratory secretions can be purulent, significant in quantity, and associated with on-and-off bright red blood, pulmonary infection

acute melioidosis may range from bronchitis to severe community-acquired rapidly progressive necrotizing pneumonia, often of the upper lobes with or without metastatic abscesses that coalesce

acute septicemic melioidosis is the most severe complication of the infection. It presents as a typical sepsis syndrome with hypotension, high cardiac output, and low systemic vascular resistance. In many cases, a primary focus in the soft tissues or lung can be found. The syndrome, usually in patients with risk factor comorbidities, is characteristically associated with multiple abscesses involving the cutaneous tissues (nodule , lymphangitis , lymphadenitis ),meningitis , gastroenteritis , the lung, the liver, and spleen and a very high mortality rate of 80-95%. With prompt optimal therapy, the case fatality rate can be decreased to 40-50%

chronic suppurative melioidosis includes skin ulcers not healing, abscesses in skin, lung abscess => cavities (may resemble cavitary tuberculosis), brain, liver, spleen, bones, joints, lymph nodes and eye

=> 'reactivation' disease in the lungs and elsewhere even 26 years after exposure !
Laboratory examinations : recognizing the disease depends on awareness on the part of clinicians and on the ability of microbiology laboratories to identify the causative organism^ref1,
ref2. Diagnosis also depends on appropriate specimens being sent to the laboratory. Some clinicians routinely request blood cultures from patients with high fever before starting antimicrobial drugs, although in practice, the specimen is often collected by nursing staff after the 1st dose has already been administered. Other clinicians only request blood cultures if fever persists after a few days of empiric antimicrobial therapy. Prior administration of cefotaxime may delay B. pseudomallei culture from blood until 5 days of incubation, when the median time to obtain a positive blood culture result is typically 48 hours^ref. After 5 days of incubation, an oxidase positive Gram negative bacillus is isolated from blood cultures. It produced colonies that appear dry and rugose on the plates after 48 h and was identified as B. pseudomallei by using API 20NE (BioMerieux, Marcy l'Etoile, France) with the profile 1156577.
Therapy : usually susceptible to tetracyclines (doxycycline

), chloramphenicol

, cotrimoxazole

, antipseudomonal penicillins (piperacillin), carbapenems (meropenem, imipenem

), cephalosporins

(ceftazidime

(ceftriaxone

and cefotaxime

have good in vitro activity but poor efficacy; and cefepime did not appear, as well, to be equivalent to ceftazidime in a mouse model)), and amoxicillin/clavulanate (clavamox

) or ampicillin/sulbactam

. Resistance to polymyxin E / colistin

, polymyxin B

, ampicillin, cephalexin, ciprofloxacin and the aminoglycosides

(gentamicin). A large zone of inhibition is seen around the trimethoprim/sulfamethoxazole disc, within which a thin film of growth was observed.

a commonly recommended initial parenteral therapy for severe disease is a 10- to 14-day course of ceftazidime or imipenem followed by oral doxycycline plus cotrimoxazole and often chloramphenicol to finish 20 weeks of treatment -- the chloramphenicol for the first 8 weeks. This prolonged course is to diminish the risk of relapse
in mild infections, an entirely oral course can be used
the formerly standard therapy of chloramphenicol , doxycycline , and cotrimoxazole combination had a higher mortality rate than therapy with ceftazidime , imipenem/cilastatin , or parenteral amoxicillin/clavulanate (or ampicillin/sulbactam ). The b-lactam-b-lactamase inhibitor therapy, however, seemed to have a higher failure rate
these penicillin-b-lactamase inhibitors, as available, are also used for oral follow up therapy.

It is considered by CDC as a category B biological weapon

: it should be noted that bioterrorism strains may be engineered to be even more resistant
Prognosis : mortality = 22%
Prevention :

wearing waterproof footwear and protective gloves when handling soil in the Wet.
there is no commercially available vaccine for melioidosis prevention in man, although experimental vaccines are under development and have been used in animals. A conjugate of flagellin and lipopolysaccharide has been found to produce IgG antibodies that protected diabetic rats from a challenge with heterologous B. pseudomallei^ref. Antibodies against the LPS II of the organisms seemed to correlate with human survival from melioidosis when examined retrospectively^ref. Since B. thailandensis is much less virulent that B. pseudomallei, Reickseidler et al used subtraction hybridization to analyze virulence factors^ref. The capsular polysaccharide seemed to represent a major virulence determinant and capsular mutants in a mouse model did not seem to be protective for subsequent wild-type challenge. Indeed, since the attenuation of B. thailandensis is stable, it might be useful as a live, attenuated vaccine itself. B. pseudomallei auxotrophic mutants are also attenuated and have been found to be protective in a mouse model^ref. Vaccines for melioidosis have recently been reviewed by Warawa and Woods^ref