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Published Date: 2004-09-17 23:50:00
Subject: PRO/EDR> Melioidosis - Singapore (04)
Archive Number: 20040917.2578

MELIOIDOSIS - SINGAPORE (04)
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Date: Fri 17 Sep 2004
From: ProMED-mail <promed@promedmail.org>
Source: Straits Times, Singapore [edited]
<http://www.straitstimes.asia1.com.sg/home>

A soil-borne bacterium, causing melioidosis, has killed 24 of the 79
people infected here [Singapore] so far in 2004, a 3-fold rise in the
death rate for the disease.
The overall death rate has jumped from 10 percent of those infected
in 2003 -- 4 deaths out of the 40 -- to about 30 percent this year
[2004], MOH statistics show. The high death rate has led the Ministry
of Health (MOH) to investigate whether the disease was being caused
intentionally, since the bacterium (_Burkholderia pseudomallei_) is a
known agent for potential biological warfare. Fortunately, it was not
caused intentionally: different patients were seen to have different
strains of the bacterium, said Professor K. Satkunanantham, director
of medical services in the ministry.
Professor Satkunanantham, who addressed the World Melioidosis
Congress here [Singapore] yesterday, 16 Sep 2004, said that the death
rate from the disease between January and July 2004 was 3 times that
of SARS. The overall death rate during that period was 40 percent. In
the same time period, SARS, by comparison, had a death rate of 13
percent.
Despite such alarming figures, there is no need to panic, said the
deputy director of the MOH's disease control branch, Dr. Ooi Peng
Lim. He said that 80 percent of those who died had existing health
problems, such as diabetes and hypertension, which are known to
reduce immunity. More than 75 percent of the victims were over 45.
The biggest outbreak -- involving 19 people -- occurred during heavy
rains in March 2004, which brought the bacterium, usually buried in
the soil, to the surface. The rains were the heaviest recorded since
1913, said Dr. Ooi, and this may have been a factor.
Doctors and scientists continue to be baffled by the disease, because
so little is known about it. Dr. Eric Yap of the Defense Science
Organization (DSO), a leading researcher in the field from Singapore,
said "the disease has many different strains and often resists common
antibiotics. There are no vaccines so far."
The DSO has been at the forefront of melioidosis research because of
its potential to affect SAF soldiers in training. Another researcher,
Dr. Patrick Tan of the Genome Institute of Singapore, said that there
was still little evidence to show how the infection could stay
dormant for years in some patients and appear quickly in others, and
why some people who are exposed to the bacterium get infected, while
others do not.
But, some of these questions are likely to be answered soon.
Scientists from Britain's Sanger Institute announced that they had,
for the 1st time, identified all the 6000 genes of the bacterium
which causes melioidosis. This "genetic atlas," said the institute's
Dr. Matthew Holden, will help scientists understand how it causes the
disease and develop better diagnostic tools, drugs, and vaccines.
Dr. Yap and his colleagues from the DSO National Laboratories have
developed a tool, a DNA micro-array, that lets scientists study all
the genes of the melioidosis bacterium at the same time. Previously,
they could study only one or 2 genes at a time. "We hope to
understand how the bacterium causes the disease and identify genes
that are particularly virulent," he said. "That will help us target
treatment better."
Melioidosis is caused through direct contact of bruised skin with the
soil, leading to abscesses and conditions such as septicemia, or
blood poisoning, in which people with low immunity are felled by
bacteria that enter their bloodstream. The melioidosis bacterium
lives mostly in clay soils, 25 to 45 cm deep, but monsoon rains can
bring it to the surface.
--
ProMED-mail
<promed@promedmail.org>
[_Burkholderia pseudomallei_ exists as an environmental saprophyte
living in soil and surface water in endemic areas (South East Asia
and northern, tropical Australia), particularly in rice paddies. In
endemic countries, the organism exists primarily in focal areas and
is not equally distributed throughout the landscape. Sporadic cases
have been reported to have been acquired in parts of Africa and the
Americas. 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. 2 outbreaks in Australia have also implicated potable water
supplies, rather than surface water, as a potential source of the
infection.
Melioidosis is a disease of the rainy season in endemic areas. It
mainly affects people who have had direct contact with soil and
water. Many have an underlying predisposing condition, such as
diabetes (the most common risk factor), renal disease, cirrhosis,
thalassemia, alcohol dependence, immunosuppressive therapy, chronic
obstructive lung disease, cystic fibrosis, or, 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.
The most commonly recognized presentation of melioidosis is
pneumonia, associated with high fever, significant muscle aches,
chest pain, and -- although the cough can be nonproductive --
respiratory secretions that can be purulent, significant in quantity,
and, associated with on-and-off bright red blood. The lung infection
can be rapidly fatal -- with bacteremia and shock -- or somewhat more
indolent.
Acute melioidosis septicemia 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, the lung, the liver, and spleen, and, a very high
mortality rate of 80 to 95 percent. With prompt optimal therapy, the
case fatality rate can be decreased to 40 to 50 percent.
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 (SXT), antipseudomonal penicillins,
carbapenems, ceftazidime, and amoxicillin/clavulanate or
ampicillin/sulbactam. 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. The unusual
antimicrobial profile of resistance to colistin and polymyxin B and
the aminoglycosides, but, sensitivity to amoxicillin/clavulante, is a
useful tool to consider in treatment of infection with the organism.
The randomized and quasi-randomized trials comparing melioidosis
treatment have been reviewed, and it was found that the formerly
standard therapy of chloramphenicol, doxycycline, and SXT combination
had a higher mortality rate than therapy with ceftazidime,
imipenem/cilastatin, or amoxicillin/clavulanate (or
ampicillin/sulbactam). The beta lactam/beta lactamase inhibitor
therapy, however, seemed to have a higher failure rate.
Source: Tolaney P, Lutwick LI. Meliodosis. In: Lutwick LI, Lutwick SM
(eds). Bioterror: the weaponization of infectious diseases. Totowa,
NJ: Humana Press, (in press). - Mod.LL]

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