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Published Date: 2004-08-04 23:50:00
Subject: PRO/EDR> Undiagnosed illness - Taiwan (03): meliodosis
Archive Number: 20040804.2133

UNDIAGNOSED ILLNESS - TAIWAN (03): MELIOIDOSIS
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Date: Tue 3 Aug 2004
From: ProMED-mail <promed@promedmail.org>
Source: Taipei Times [edited]
<http://www.taipeitimes.com/News/front/archives/2004/08/03/2003181502>

Center explains demise of student
-----------------------------------
Faced with an avalanche of inquiries into the cause of a military school
student's death last week [final week of July 2004], the Center for Disease
Control yesterday, Mon 2 Aug 2004, confirmed that he died of melioidosis,
raising concerns over the disease's impact. According to the center, the
endemic illness is caused by a bacterium called _Burkholderia
pseudomallei_, which is most commonly found in Southeast Asia and northern
Australia. People acquire the infection by inhalation of infected dust,
ingestion of affected water, and contact with contaminated soil through
skin abrasions. Person-to-person transmission rarely occurs.
"Despite the disease not being common in Taiwan, and its initial mild
symptoms, the bacteria could invade a person's bloodstream and deteriorate
organs. Once it develops into acute bloodstream infection, and chronic
suppurative infection, it could be fatal," Chiu Chan-hsien, director of the
center's division of emerging infectious diseases, said at a press
conference in Taipei.
In the last 4 years in Taiwan, 3 people died, out of the 36 reported cases,
of melioidosis. Among the 57 suspected reported cases of melioidosis, 9
patients came from Kaohsiung County, where the tropical climate aids the
breeding of bacteria. Because of the disease's wide spectrum of clinical
symptoms, and its prolonged incubation period, ranging from 2 days to 25
years, the chance of early identification is fairly low. Also, since
melioidosis is diagnosed by isolating _Burkholderia pseudomallei_ from
blood, saliva, or skin lesions in a laboratory, doctors can hardly yield
accurate diagnoses on the spot.
In this fatal case, health professionals failed to detect the disease in
time. On 21 Jul 2004, the Kaohsiung Armed Forces General Hospital reported
the ailment, to the health bureau, as Q fever. 2 days later, the
19-year-old student was transferred to the Kaohsiung Medical College
Hospital, which reported a host of possible diseases to the center. On 24
Jul 2004, when local health officials arrived to collect tissue samples
from the patient, he had already succumbed to the illness.
"Although there is no delay in our reporting system, our staff and hospital
workers are not alert enough to identify infectious diseases. We need to
reinforce our staff training and raise public awareness of any new threat,"
said the center's deputy director-general, Shih Wen-yi.
"There is no vaccine for melioidosis so far. If it is discovered early, we
can prescribe antibiotics, and, predict any long-term sequellae," said
Chang Shan-chwen, chief of National Taiwan University's infectious disease
section. The center said that the other 23 student patients were not
infected by the bacteria. They have recovered from fever and respiratory
symptoms. 5 students were discharged from the hospital last weekend [31 Jul
- 1 Aug 2004] and are now under medical surveillance. To further verify the
cause of the students' illness, the center will draw blood samples after 2
weeks.
"The student who died is an isolated case. Other students are on the mend,"
the school's army officer, Fan Yu-chuan, told the Taipei Times.
"Our exercises do not expose students to the bacteria. Our students wear
long-sleeved shirts, long pants and boots when they practice fieldwork.
Even if they have wounds, they are well protected from possibly
contaminated soil."
Farmers who work in paddies barefoot, and patients with weakened immune
systems or wounds, are vulnerable to the disease. With no effective
preventive measures, the center called for the public to properly clean any
wounds and avoid contact with contaminated water and soil.
[Byline: Wang Hsiao-wen]
--
ProMED-mail
<promed@promedmail.org>
[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, and,
that it can also cause 'reactivation' disease in the lungs, and elsewhere,
years, even decades after exposure.
The disease is endemic in South East Asia and, 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 (2). 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. _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 being
given for the first 8 weeks. This prolonged course is to diminish the risk
of relapse.
Many infections are entirely asymptomatic, but, can present as
undifferentiated febrile illness, or, with fever and respiratory symptoms
(as in what may have occurred here). In mild, but recognized, 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.
There is no commercially available vaccine for melioidosis prevention in
humans, 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_ (3). Antibodies against the
LPS II of the organisms seemed to correlate with human survival from
melioidosis when examined retrospectively (4).
Since _B. thailandensis_ is much less virulent that _B. pseudomallei_,
Reickseidler et. al. (5) 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).
This may well just be a single fatal, septicemic case of melioidosis in the
setting of a cluster of febrile illness due to another cause. It is
disconcerting, however, because
1 - Fatal septicemic cases of melioidosis occur primarily in individuals
with underlying risk factors such as diabetes, renal failure, or emphysema.
None were stated to be present here;
2 - In murine data, septicemic disease is more common in distinctly high
inocula of exposure, as might occur in an intentional exposure; and
3 - Most primary infections with _Burkholderia pseudomallei_ (formerly
_Pseudomonas pseudomallei_) [in the earlier posting of this case prior to
correct identification -20040730.2075, the organism was referred to as a
pseudomonad] are either asymptomatic, or, associated with undifferentiated
febrile illnesses or pneumonia.
Although it is stated that the other students did not have melioidosis,
cultures are often negative in mild disease, and the diagnosis may need to
be serological in nature. Since melioidosis is not particularly common in
the area of these cases, antibody tests for the organism may be helpful here.
1. White NJ. Melioidosis. Lancet 2003; 361: 1715-22.
2. 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.
3. Brett PJ, Woods DE. Structural and immunological characterization
of Burkholderia pseudomallei O-polysaccharide-flagellin protein
conjugates. Infect Immun 1996; 64: 2824-28.
4. Charuchaimontri C, Suputtamongkol S, Nilakul C, et al.
Antilipopolysaccharide II: an antibody protective against fatal
melioidosis. Clin Infect Dis 1999; 29; 813-8.
5. 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.
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: 477-82. - Mod.LL]

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