Published Date: 2003-12-17 23:50:00
Subject: PRO/EDR> Melioidosis - Australia (Northern Territory)
Archive Number: 20031217.3084
MELIOIDOSIS - AUSTRALIA (NORTHERN TERRITORY)
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Wed, 17 Dec 2003
Source: News.com.au 14 Dec 12003 [edited]
A Top End [from the Northern Territories - Mod.LL] mother, 47, with
melioidosis is still in intensive care in the Royal Darwin Hospital after
doctors were forced to amputate her limbs to prevent the disease from
killing her. The woman became ill early last month and underwent the
operation later last month.
Melioidisis, also known as Nightcliff Gardeners' Disease, is caused by the
bacteria _Burkholderia pseudomallei_. The bacterium is generally found in
mud and damp soil. It enters the body through cuts and sores, or is inhaled
in dust droplets or ingested through contaminated water [and only very
rarely from person to person - Mod.LL].
Nine people were hospitalized with the disease last Dry [the dry season -
Mod.LL]. The previous highest number in any Dry was 4. Experts say 30
people will contract the disease in the Wet [correspondingly the wet season
- Mod.LL], and 5 will die. Infectious disease specialist Dr Dale Fisher
said the risk of contracting melioidosis would increase in the wet season.
He said symptoms include signs of pneumonia such as shortness of breath and
cough, sputum production, and skin ulcers not healing. "It's clear most
exposures occur through the skin," he said. "An important feature would be
fever, particularly if people have fevers without an obvious source. Those
people definitely need to be assessed."
Those most at risk are immunosuppressed groups, including heavy drinkers,
diabetics and patients with renal or lung disease, cancer, or on
corticosteroid therapies. There is no vaccine but you can lessen infection
by wearing waterproof footwear and protective gloves when handling soil in
[As a category B biowarfare agent, it is reasonable to post natural cases
of this infection periodically as well as outbreaks to remind us about this
potentially fatal disease that can be a cause of severe community-acquired
pneumonia with or without metastatic abscesses or can cause 'reactivation'
disease in the lungs and elsewhere years, even decades after exposure.
The disease was first described in Rangoon, Burma (now Myanmar) by Whitmore
and Krishnaswami in 1912 among homeless, debilitated morphine addicts.
Autopsies performed on the remains of these individuals revealed a process
reminiscent of glanders, an abscess-forming infection of horses and, quite
rarely now, man. Microbiologically, the physicians from Her Majesty's
Indian Health Service could distinguish the isolated organism from the
glanders bacterium and others. The term melioidosis as related by White (1)
was coined by Fletcher and Stanton from Kuala Lumpur, Malaysia from the
Greek words melis (a distemper of asses) and eidos (resemblance). 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. Later, during the Vietnamese
war of independence with France and, more so, the United States
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
Also a disease of animals, 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 (1), 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, but cases have been described in the western
hemisphere without travel histories as well. There are some _B.
pseudomallei_-like organisms that are much less virulent. Formerly
considered to be a separate biotype, these L-arabinoside assimilators are
now classified as _B. thailandensis_ and account for about a quarter of
soil isolates in Thailand (M5). This is a hard-core survivalist organism
that can persist in triple-distilled water for long periods of time.
The melioidosis bacillus is intrinsically insensitive to many
antimicrobials. It should be noted that bioterrorism strains may be
engineered to be even more resistant. _B. pseudomallei_ is usually
inhibited by tetracyclines, chloramphenicol, trimethoprim-sulfamethoxazole,
antipseudomonal penicillins, carbapenems, ceftazidime (ceftriaxone and
cefotaxime have good in vitro activity but poor efficacy), and
amoxicillin/clavulanate or ampicillin/sulbactam. 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
trimethoprim-sulfamethoxazole 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.
Amoxicillin/clavulanate or ampicillin/sulbactam can be used, as available,
as initial parenteral therapy but has a higher failure rate. These
penicillin-betalactamase inhibitors, as available, are also used for oral
follow up therapy.
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_ (2). Antibodies against the
LPS II of the organisms seemed to correlate with human survival from
melioidosis when examined retrospectively (3).
Since _B. thailandensis_ is much less virulent that _B. pseudomallei_,
Reickseidler et al (4) used subtraction hybridization to analyze virulence
factors. 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 (5). 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 (6).
Vaccines for melioidosis have recently been reviewed by Warawa and Woods (7).
1. White NJ. Melioidosis. Lancet 2003; 361: 1715-22.
2. Brett PJ, Woods DE. Structural and immunological characterization of
Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates.
Infect Immun 1996; 64: 2824-28.
3. Charuchaimontri C, Suputtamongkol S, Nilakul C, et al.
Antilipopolysaccharide II: an antibody protective against fatal
melioidosis. Clin Infect Dis 1999; 29; 813-8.
4. Reckseidler SL, DeShazer D, Sokol PA, Woods DE. Detection of bacterial
virulence genes by subtractive hybridization identification of capsular
polysaccharide of _Burkholderia pseudomallei_ as a major virulence
determinant. Infect Immun 2001; 69: 34-44.
5. Atkins T, Prior R, Mack K, et al. Characterisation of an acapsular
mutant of Burkholderia pseudomallei identified by signature tagged
mutagenesis. J Med Microbiol 2002; 51: 539-47.
6. Atkins T, Prior RG, Mack K, et al. A mutant of _Burkholderia
pseudomallei_, auxotrophic in the branched chain amino acid biosynthetic
pathway, is attenuated and protective in a murine model of melioidosis.
Infect Immun 2002; 70: 5290-4.
7. Warawa J, Woods, DE. Melioidosis vaccines. Expert Rev Vaccines 2002; 1: