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Sara Dong: Hi, everyone.

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Welcome to Febrile, a cultured podcast
about all things infectious disease.

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We use consult questions to dive into
ID clinical reasoning, diagnostics,

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and antimicrobial management.

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I'm Sara Dong, your host
and a MedPeds ID doc.

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I am super pumped to bring you
another international episode today.

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We are joined by a team from Australia.

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First up, I'll introduce our host, Dr.

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Genevieve Martin.

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She is undertaking her training in
ID at the Royal Darwin Hospital in

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the Northern Territory, Australia.

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She completed her PhD in the
immunology of early HIV infection

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and HIV cure approaches at the
University of Oxford in 2018.

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Genevieve Martin: Hi, my
name is Genevieve Martin.

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I'm an infectious diseases registrar
at the Royal Darwin hospital, and

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I'm really glad to be here today.

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Sara Dong: We have two
additional consultants today.

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Dr.

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Catherine Marshall is the co
director of the Department of

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Infectious Diseases and is an ID
physician at Royal Darwin Hospital.

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Catherine Marshall: I'm Dr.

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Catherine Marshall, the co director
of Infectious Diseases at Royal Darwin

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Hospital, and I'm thrilled to be here.

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Thanks.

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Sara Dong: And we are also joined by
Professor Bart Currie, who is an ID

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physician at Royal Darwin and also works
in the Menzies School of Health Research.

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Bart Currie: Good morning or good
evening, I'm Bart Currie, an infectious

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disease physician here at Royal Darwin
Hospital and also working at the

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Menzies School of Health Research.

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Thank you.

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Sara Dong: Great.

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I'm so excited you guys are here.

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Before we jump in, we always
ask one quick question.

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As everyone's favorite cultured podcast,
I'd love to hear you share a little

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piece of culture, you know, something
that brings you joy outside of work.

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Genevieve Martin: It's early days to
call it something good, but I've just

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started reading The Bee Sting by Paul
Murray, and I think it's going to be good.

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Catherine Marshall: So one of my favourite
things to do in Darwin each year is to

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visit the National Aboriginal and Torres
Strait Islander Art Awards that are shown

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at the Museum and Art Gallery of the
Northern Territory, and there's a fabulous

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array of art from all over the country.

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Genevieve Martin: Oh, it's great.

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I went a couple of weeks ago.

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Bart Currie: My naturalist colleagues
here up in the tropical north of

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Australia have told me that the snakes
have been very unusual in their behavior

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over the last three or four months.

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They've been on the move and they've
also been, the newborns have been

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hatching or the eggs have been hatching
and the liveborns have been coming,

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coming out earlier than normal.

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We've had a substantial number of bites
from snakes in the last few months,

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more than I think we've ever seen.

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Genevieve Martin: In addition
to being an infectious disease

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physician, Bart Currie is also our
snake bite management expert up here.

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Bart Currie: I guess it is
mixing work with pleasure.

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Sara Dong: Well, thank you
guys so much for sharing.

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Genevieve, well, I'm looking forward
to hearing about your consult.

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Genevieve Martin: Okay, perfect.

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This scenario is, you receive a call
in late January, the wet season,

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from the emergency department that
a 42 year old male has arrived,

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having been flown in from a remote
community in the Northern Territory.

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The patient's being brought into
his local clinic by family members.

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History reveals two to three days
of cough and subjective fevers.

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The observations taken in the
remote clinic showed a fever of 38.

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9 degrees Celsius, tachycardia
at 108 beats per minute, a blood

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pressure of 109/62, and a respiratory
rate of 28, meeting SIRS criteria.

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One set of blood cultures was taken
and the patient was given a stat dose

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of ceftriaxone and gentamicin, along
with crystalloid fluid resuscitation.

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Having now arrived in the ED, he
remains tachypneic and tachycardic

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with a GCS of 14, scored for confusion.

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He is now requiring 2 litres
of oxygen to maintain oxygen

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saturations greater than 94%.

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Initial blood work is
taken and is pending.

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At this point, what further
information would you like, and what

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investigations would you suggest that
the emergency department request?

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Catherine Marshall: Thanks Genevieve.

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So I guess I would be concerned that
this patient has bacterial sepsis due

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to a lower respiratory tract infection
and I would want to know what their

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comorbidities were and whether they were
a smoker or a heavy drinker of alcohol.

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We know that excessive alcohol
consumption is a risk factor for

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both melioidosis and community
acquired Acinetobacter infection.

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I'd also want to know whether they've
had any water or animal exposures that

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would put them at risk of infections
such as leptospirosis or Q fever,

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and I'd want to know whether they've
had any recent skin infections or

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abscesses that may indicate a risk for
disseminated Staph aureus infection.

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I'd recommend that the emergency
department undertook further blood

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cultures, sputum and urine cultures,
and a chest x ray in the first instance.

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In our emergency department,
they'd also do a gene expert

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PCR for COVID/Influenza/RSV.

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I'd also suggest sending serology
for melioidosis, and we also do a,

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or recommend a throat and rectal
swab that is then incubated in a

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selective media called Ashdown's Media,
looking specifically for melioidosis.

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Given the confusion in this patient, I
think that they're going to likely need

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imaging of the brain with at least a
CT scan and probably a lumbar puncture

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to exclude a meningoencephalitis
after they're stable from an initial

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resuscitation perspective, and I
guess although less likely, I may also

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suggest sending a blood and urine for
say, leptospirosis PCR, and serology.

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Genevieve Martin: Well, we
have some of that information.

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So in terms of past medical history,
the emergency department staff have been

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unable to identify any relevant past
medical history, and they've confirmed

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that the, the patient, uh, does not, has
very little contact with his local clinic.

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With regards to alcohol use, they've
spoken with family who've reported

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that he does not drink any alcohol
and is not a smoker, but that he

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does spend a lot of time fishing
in the rivers around the community.

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Initial blood work is now back, which
shows a raised white cell count at 23.

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2 with a predominant neutrophilia and a
C reactive protein at 391 mg per litre.

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His creatinine is elevated at 156
giving a GFR of 46 with a lactate of 3.

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2, ketones 2.

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4 and sodium 129.

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He has a normal bilirubin of 7
with liver enzyme derangement

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that's predominantly cholestatic.

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The patient's noted to have a
macrocytic anemia with a hemoglobin

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of 110 and an MCV of 105.

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Chest X ray shows bilateral consolidation
and neuroimaging is still pending.

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Despite a further 2 litres of fluid
resuscitation, he remains hypotensive

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and is being transferred to the intensive
care unit for vasopressor support.

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At this stage, what empiric
antimicrobials would you suggest and why?

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Catherine Marshall: So I would initially
recommend treatment for severe community

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acquired pneumonia, which according to
our local guidelines in the wet season

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would include a combination of meropenem
that covers the usual well known organisms

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that cause community acquired pneumonia
such as streptococcal pneumoniae.

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But we'll also cover Burkholderia
pseudomallei, the agent causing

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melioidosis, and community acquired
Acinetobacter baumannii, which also

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can be a cause of community acquired
pneumonia in our tropical region.

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And that would also provide
cover for leptospirosis.

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I'd also recommend vancomycin to
cover for MRSA, and azithromycin

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to provide some atypical cover,
particularly thinking of Legionella.

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Genevieve Martin: Okay,
thank you for that.

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So the patient's been admitted to
the intensive care unit, and on your

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advice has been commenced on meropenem,
vancomycin, and azithromycin, but has

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an ongoing noradrenaline requirement.

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He's requiring oxygen via nasal
prongs, but no additional respiratory

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supports, and has been commenced
on an insulin infusion to assist in

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management of hyperglycemia and ketosis.

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An HbA1c has just returned at 10.

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2%, consistent with
undiagnosed diabetes mellitus.

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The intensive care team have received a
phone call to say that a blood culture

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taken in community is growing in atypical
motile gram negative bacillus, which

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they suspect may be a contaminant.

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The two further sets taken
in the emergency department

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remain negative at this stage.

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Based on this information, Burkholderia
pseudomallei is strongly suspected

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to be the causative organism.

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I'm wondering, Bart, if you could
tell us a little bit more about the

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additional diagnostic tests that
might be available at this stage

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to help us confirm the diagnosis.

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Bart Currie: Yes, thanks Genevieve.

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So, melioidosis is always diagnosed
still by having a culture.

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That's the only thing that will
fulfill the definition of confirmed

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melioidosis is a laboratory culture
for Burkholderia pseudomallei.

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The organism was thought by the
laboratory initially, not our hospital

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laboratory, but the external laboratory,
to maybe be a contaminant, which is

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not unusual for places where they may
not see this organism so commonly.

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So, the thing about the organism is
that it's a motile gram negative rod,

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it's oxidase positive, non lactose
fermenting, and it has bipolar staining.

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In laboratories which do not have a
lot of resources, there's a 3 disk

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diffusion test that can be used,
which is using gentamicin, to which

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Burkholderia pseudomallei is resistant,
and also colistin disc, and also an

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amoxicillin cladolanic acid disc.

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And Burkholderia pseudomallei is
sensitive to amoxi-clav, but resistant

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to gentamicin and colistin, so that
three disc test has been very useful

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to make people think that this is B.

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pseudomallei.

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Then to confirm that the organism is B.

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pseudomallei, there have traditionally
been various biochemical profiles,

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but there are also automated
tests such as Vitek and MaldiTOF.

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The problem with Vitek and MaldiTOF, and
there have been a number of publications

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over the years, is that historically,
they would sometimes misidentify B.

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pseudomallei as another Burkholderia
species or indeed some other organisms,

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but more recently, with improved database
profiles, such as an increased number

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of mass spectra profiles in the MALDI
TOF, the specificity of these automated

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detection systems have been much
improved, so that the final confirmation

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can be made on those systems usually.

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However, in addition to that, there is
also the ability to do a PCR on a culture

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and also there is a non commercial
lateral flow assay that can be used.

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Genevieve Martin: Okay.

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Fantastic.

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That's really helpful.

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So to return briefly to the case, based
on some advice provided by our team, some

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further investigations are performed.

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A CT of the chest and abdomen and pelvis
is performed revealing a dense right

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sided consolidation and left middle
zone changes without any cavitation

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or associated pleural effusion.

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There is evidence of multiple
splenic hypodensities reported to

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favour infection or infarction.

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This CT has also identified a very large
24 by 18 millimetre prosthetic abscess.

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Urology have been referred
to consider drainage of this.

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And the urine sent on admission
has greater than 100 leukocytes on

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microscopy and is now growing a motile
gram negative organism with bipolar

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staining, which the lab has confirmed
is morphologically consistent with

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Burkholderia pseudomallei, and a PCR of a
throat rectal swab cultured in Ashdown's

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media is also positive for this organism.

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Together, these investigations
confirm a diagnosis of melioidosis.

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What is your approach to the initial
management of this infection?

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Catherine Marshall: Thanks Genevieve.

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So I think we'd be comfortable now
that this patient, as you mentioned,

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has disseminated melioidosis with
involvement with pneumonia, likely

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splenic abscesses and a prostatic abscess.

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So, our initial management would include
appropriate antimicrobial therapy,

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which would be intravenous in the
first instance with either meropenem

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or ceftazidime, and we usually prefer
meropenem in the intensive care setting.

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Given that there's deep abscesses,
particularly in the prostate, we

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would also add a second agent, so
cotrimoxazole, as, you know, additional

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agent to improve penetration,
particularly within the prostate.

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The other critical component of initial
management is source control, so in

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this case we would recommend drainage
of the prostatic abscess, which might

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be done either by the urologist or is
sometimes done by our radiology colleagues

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transrectally using ultrasound guidance.

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There would also need to be assessment
of the splenic abscess about whether

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that would need further drainage,
but often we can manage those

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conservatively with antibiotics alone.

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Genevieve Martin: On day four of
ICU admission, the patient's being

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weaned off inotropic support with
improving inflammatory markers.

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Atraumatic swelling of the left knee
is noted and a diagnostic aspirate

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performed at the bedside reveals a
synovial white cell count of 38, 000

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cells with no organisms or crystals seen.

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Burkholderia pseudomallei PCR
and a lateral flow assay for the

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Burkholderia pseudomallei antigen
on synovial fluid is positive.

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How frequently is musculoskeletal
involvement encountered and does

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this change your management?

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Bart Currie: Thanks Genevieve.

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So just taking a step back, this,
this patient represents the severe

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end of the spectrum of melioidiosis.

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So it's a person who has severe sepsis,
they're bacteremic, and the organism is

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primarily probably caused a pneumonia
initially and then seeded to prostate,

225
00:12:28,610 --> 00:12:32,150
spleen, and now, as evident, to a joint.

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00:12:32,760 --> 00:12:37,300
Overall, over half of the patients who
present with melioidiosis are bacteremic,

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00:12:37,940 --> 00:12:42,740
and the primary presentation in around
half of the patients is a pneumonia,

228
00:12:42,820 --> 00:12:44,389
with subsequent seeding in some of them.

229
00:12:44,939 --> 00:12:49,225
Overall, 21 percent of the patients
do present like this with septic shock

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00:12:49,225 --> 00:12:50,805
requiring intensive care management.

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00:12:51,015 --> 00:12:54,765
Then the lesser end of the spectrum of
presentation, which is not this patient,

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00:12:54,815 --> 00:12:58,275
are people who may have a primary
skin lesion without systemic sepsis

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00:12:58,825 --> 00:13:03,214
or people presenting primarily with a
genitourinary infection where the prostate

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00:13:03,214 --> 00:13:07,535
abscess may be the initial presentation
rather than having seeded there, with

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00:13:07,535 --> 00:13:09,325
pneumonia being the primary presentation.

236
00:13:09,875 --> 00:13:14,255
So overall, in answer to the
question, septic arthritis is very

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00:13:14,255 --> 00:13:17,889
rare as a primary presentation,
around about 3 percent of our cases.

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00:13:18,189 --> 00:13:22,869
And osteomyelitis, even less common,
1 percent of our primary cases, but

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00:13:23,259 --> 00:13:27,040
within the three weeks following
initial presentation, seeding to bone

240
00:13:27,040 --> 00:13:29,259
and joint is certainly well recognized.

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00:13:29,319 --> 00:13:33,259
So an additional 3 percent of
patients will seed to joints,

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00:13:33,329 --> 00:13:37,949
such as in this patient, 3 percent
seed to joint with osteomyelitis.

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00:13:38,380 --> 00:13:42,500
And we also have seeding to muscles,
so muscle abscesses in sometimes

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00:13:42,500 --> 00:13:46,600
multiple different muscles will present
in 3 percent of patients, subsequent

245
00:13:46,650 --> 00:13:47,850
to their initial presentation.

246
00:13:48,240 --> 00:13:50,760
So that's the spectrum of melioidiosis.

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00:13:50,779 --> 00:13:55,075
And if the way it changes management
is, is that, as Katherine mentioned,

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00:13:55,865 --> 00:14:00,315
abscesses often need to be drained and
certainly joints need to be, initially

249
00:14:00,315 --> 00:14:02,485
after the aspiration, usually washed out.

250
00:14:02,545 --> 00:14:06,435
And it's not uncommon for joints
to need to have a second washout.

251
00:14:06,724 --> 00:14:10,265
And so what we do is that we reset
the clock for the intravenous

252
00:14:10,265 --> 00:14:14,640
antibiotics every time we do an
aspirate, or a washout, or a drainage

253
00:14:14,640 --> 00:14:18,079
of an abscess, provided that it is
culture positive, which it usually is.

254
00:14:18,119 --> 00:14:21,280
So that then resets our clock
for the antibiotic duration for

255
00:14:21,280 --> 00:14:22,550
the intravenous antibiotics.

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00:14:22,829 --> 00:14:24,770
Genevieve Martin: And I guess
that leads into the next question.

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00:14:24,849 --> 00:14:28,040
Once appropriate source control has been
achieved, and we're happy that that's

258
00:14:28,040 --> 00:14:33,400
the case, the duration of antimicrobials
used for melioidiosis is much longer

259
00:14:33,400 --> 00:14:35,170
than other gram negative infections.

260
00:14:35,640 --> 00:14:38,409
How long do you need to treat for,
and what's the approach to this?

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00:14:38,920 --> 00:14:41,400
Catherine Marshall: As alluded by
Bart, the treatment of melioidiosis

262
00:14:41,420 --> 00:14:45,969
involves an intensive intravenous
phase, which is followed then by an oral

263
00:14:46,020 --> 00:14:51,030
eradication phase, and the duration of
the intensive phase varies depending on

264
00:14:51,030 --> 00:14:52,989
the source and extent of the infection.

265
00:14:53,299 --> 00:14:58,330
For a simple limited bacteremia or
limited mild pneumonia, that may be you

266
00:14:58,330 --> 00:15:00,490
know, two weeks of intravenous therapy.

267
00:15:00,830 --> 00:15:04,160
But if there is disseminated disease,
say, for example, with central

268
00:15:04,160 --> 00:15:07,139
nervous system involvement, this
may be as long as eight weeks.

269
00:15:07,639 --> 00:15:11,920
And as Bart mentioned before, time
is taken from either the date of the

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00:15:11,920 --> 00:15:16,800
last positive culture or the time that
source control has been achieved with

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00:15:16,800 --> 00:15:18,490
either, you know, drainage of an abscess.

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00:15:19,160 --> 00:15:22,920
In this case, where there are deep
collections and septic arthritis, the

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00:15:22,920 --> 00:15:27,349
patient would require a minimum of
four weeks of intravenous therapy from

274
00:15:27,349 --> 00:15:31,030
the time of source control, but if it
subsequently discovered that they had

275
00:15:31,260 --> 00:15:34,980
osteomyelitis associated with their
septic arthritis, then that would

276
00:15:34,980 --> 00:15:36,940
need to be extended to six weeks.

277
00:15:37,820 --> 00:15:42,650
Following the intravenous phase, there
is ongoing eradication therapy, which

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00:15:42,659 --> 00:15:46,770
usually involves oral cotrimoxazole
for a minimum of three months.

279
00:15:47,230 --> 00:15:50,070
That would be extended out to
six months if there were CNS

280
00:15:50,070 --> 00:15:51,790
involvement or osteomyelitis.

281
00:15:52,365 --> 00:15:55,765
If cotrimoxazole is not
tolerated, then doxycycline is

282
00:15:55,765 --> 00:15:57,285
used as a second line therapy.

283
00:15:57,564 --> 00:16:01,165
Genevieve Martin: This patient is
improving and nearing discharge from

284
00:16:01,265 --> 00:16:04,395
our hospital in the home service,
having completed six weeks of

285
00:16:04,405 --> 00:16:06,634
intravenous therapy with ceftazamine.

286
00:16:07,214 --> 00:16:10,825
They've been established on
trimethoprim-sulfamethoxazole at a

287
00:16:10,845 --> 00:16:15,695
high dose of 320 / 1600 milligrams
orally twice a day with additional

288
00:16:15,695 --> 00:16:17,035
folic acid supplementation.

289
00:16:17,165 --> 00:16:20,265
They're tolerating this regimen well
with no significant adverse reactions.

290
00:16:21,305 --> 00:16:25,395
They ask you why they became sick with
this infection in the first place.

291
00:16:26,205 --> 00:16:29,515
How do you counsel them about risk
factors and prevention of infection?

292
00:16:30,175 --> 00:16:33,475
Bart Currie: I think that taking a
step back in, in relation to prevention

293
00:16:33,485 --> 00:16:37,514
of melioidiosis, which would also
be the information passed on to this

294
00:16:37,515 --> 00:16:42,005
patient because people can get a
second infection with melioidiosis.

295
00:16:42,224 --> 00:16:45,795
What we have recognized over time with
our studies here in Darwin is that

296
00:16:46,005 --> 00:16:50,944
melioidiosis is very much considered as an
opportunistic infection, so healthy people

297
00:16:50,944 --> 00:16:53,685
rarely get very sick from melioidiosis.

298
00:16:53,920 --> 00:16:57,660
And indeed, only 16 percent of
our cases are people who have

299
00:16:57,690 --> 00:16:59,230
identified clinical risk factors.

300
00:16:59,895 --> 00:17:03,935
So that our emphasis for public health
is on the people who have the risk

301
00:17:03,935 --> 00:17:08,395
factors and for them to avoid exposure
to the organism during the wet season

302
00:17:08,474 --> 00:17:10,435
when 85 percent of our cases happen.

303
00:17:10,435 --> 00:17:15,005
Our wet season here is from basically
November through to the end of April.

304
00:17:15,395 --> 00:17:18,024
And it's during that time that the
majority of our cases happen when

305
00:17:18,054 --> 00:17:23,524
people have an exposure to wet
season, soil, mud, or surface water.

306
00:17:24,079 --> 00:17:25,280
What are those risk factors?

307
00:17:25,280 --> 00:17:29,409
Well, up to 50 percent of our cases
are people living with diabetes.

308
00:17:29,699 --> 00:17:33,749
Sometimes, diabetes has not been
diagnosed until the episode of meliodosis.

309
00:17:35,110 --> 00:17:38,679
Hazardous alcohol use is unfortunately
common in our part of the world here

310
00:17:38,710 --> 00:17:40,280
as a risk factor for meliodosis.

311
00:17:40,690 --> 00:17:44,845
And then people with chronic lung
disease, chronic kidney disease, and then

312
00:17:44,845 --> 00:17:48,525
increasingly we're seeing our patients
who have malignancies and particularly

313
00:17:48,635 --> 00:17:52,635
after they go on immunosuppression and
most notably corticosteroid therapy, they

314
00:17:52,635 --> 00:17:57,115
are people who are really magnets for
melioidiosis during the wet season and so

315
00:17:57,155 --> 00:17:58,894
for those people in the high risk groups.

316
00:17:59,435 --> 00:18:03,355
We actually recommend that when the
wind and rains come, that they stay

317
00:18:03,355 --> 00:18:07,115
indoors during periods of heavy wind
and rain because while the majority

318
00:18:07,115 --> 00:18:10,874
of infections are thought to be
percutaneous exposure through either

319
00:18:10,875 --> 00:18:16,604
cuts or trauma, there's clearly a shift
to inhalational melioidiosis when there

320
00:18:16,605 --> 00:18:21,495
is actually windy and rainy events and
so we recommend people with those risk

321
00:18:21,605 --> 00:18:25,775
factors stay indoors and if they have
to go outside they even wear a mask.

322
00:18:26,105 --> 00:18:28,920
One of the things we've found most
recently, in the last few years,

323
00:18:28,920 --> 00:18:33,480
is that people using high pressure
hoses to clean off pavements or to

324
00:18:33,480 --> 00:18:37,539
clean their cars have been getting
infected through aerosolization.

325
00:18:37,570 --> 00:18:41,170
So these are all the things that can
put people at risk of melioidiosis.

326
00:18:41,190 --> 00:18:44,925
And the final point is that
children are not at risk

327
00:18:44,955 --> 00:18:47,145
usually of getting melioidiosis.

328
00:18:47,165 --> 00:18:51,265
We of course will have the occasional
case with a single skin sore or an

329
00:18:51,265 --> 00:18:55,224
immunosuppressed child unfortunately may
well get melioidiosis and become sick.

330
00:18:55,224 --> 00:19:01,045
But overall, less than 4 percent of our
patients are children aged under 15 years.

331
00:19:01,534 --> 00:19:03,705
Genevieve Martin: I guess we've
talked a little bit about melioid

332
00:19:03,725 --> 00:19:07,024
up here in the top end, Burkholderia
pseudomallei is found in the soil

333
00:19:07,024 --> 00:19:10,504
in tropical and subtropical regions,
including the top end of Australia

334
00:19:10,504 --> 00:19:12,905
where we work in endemic areas.

335
00:19:12,905 --> 00:19:15,635
The incidence of melioidiosis,
as you've mentioned, has a

336
00:19:15,635 --> 00:19:17,285
strong link with weather events.

337
00:19:17,604 --> 00:19:20,725
What do we know about the
environmental niche of Burkholderia

338
00:19:20,995 --> 00:19:25,014
pseudomallei, and is this linked
to changing regions of endemicity?

339
00:19:25,135 --> 00:19:27,745
Bart Currie: That's a fascinating area,
and there's a lot of our colleagues

340
00:19:27,804 --> 00:19:30,834
around the world and including
in the Americas, working on this.

341
00:19:31,430 --> 00:19:34,940
Issue of what is or what are
the environmental niches for

342
00:19:34,990 --> 00:19:36,800
Burkholderia pseudomallei.

343
00:19:36,820 --> 00:19:41,279
We know that it's been endemic for
a long period of time in much of the

344
00:19:41,289 --> 00:19:44,789
tropics and subtropics and it's only
been when people have brought laboratory

345
00:19:44,949 --> 00:19:50,489
resources to regions such as in parts of
Africa and indeed in South America and

346
00:19:50,489 --> 00:19:54,060
the Caribbean that people have started
to diagnose cases of melioidiosis.

347
00:19:54,635 --> 00:19:58,805
The organism is natural to many of
these tropical environments, and

348
00:19:59,155 --> 00:20:04,195
it has a selective advantage over
other environmental organisms, in

349
00:20:04,605 --> 00:20:09,075
particularly soils which are nutrient
deplete, so poor soils with lower

350
00:20:09,075 --> 00:20:13,794
pH, where the organism is able to
survive and outcompete other organisms.

351
00:20:13,794 --> 00:20:15,395
There's a natural role in the environment.

352
00:20:15,985 --> 00:20:20,790
Its hypothesized to be in symbiosis
with the rhizosphere of various

353
00:20:20,800 --> 00:20:25,379
plants, or the root systems, where this
organism, Burkholderia pseudomallei,

354
00:20:25,400 --> 00:20:29,380
is able, through its vast array
of virulence factors, to provide a

355
00:20:29,380 --> 00:20:33,680
biodefense for those plants against
invading bacteria, fungi, and protozoa.

356
00:20:34,320 --> 00:20:40,030
The issue for the Americas is fascinating
because, while melioidiosis has

357
00:20:40,030 --> 00:20:44,845
been endemic for a long time in many
parts of the world, in the United

358
00:20:44,875 --> 00:20:49,435
States, it is now being found for
the first time to be actually endemic

359
00:20:49,454 --> 00:20:51,195
in the Gulf State of Mississippi.

360
00:20:51,195 --> 00:20:54,775
And this was published in the New
England Journal of Medicine just last

361
00:20:54,775 --> 00:21:00,605
year, following three cases in the years
between 2020 and 2023 from a particular

362
00:21:00,605 --> 00:21:02,675
county on the Gulf Coast of Mississippi.

363
00:21:02,675 --> 00:21:04,125
So this is an emerging issue.

364
00:21:04,560 --> 00:21:06,610
And our colleagues at CDC in the U.

365
00:21:06,610 --> 00:21:06,800
S.

366
00:21:06,800 --> 00:21:10,210
are working hard with the state
health authorities in Mississippi

367
00:21:10,210 --> 00:21:13,980
to find out how it got there
and how widespread it might be.

368
00:21:13,980 --> 00:21:15,919
Is it in other Gulf states
in the United States?

369
00:21:17,250 --> 00:21:19,780
What the genotyping has shown
of those bacteria is that they

370
00:21:19,780 --> 00:21:21,089
are a Western Hemisphere strain.

371
00:21:21,089 --> 00:21:26,620
So it has potentially moved from the
Americas through the Caribbean and then

372
00:21:27,230 --> 00:21:31,729
from Southern America and Caribbean
into the Southern United States.

373
00:21:32,590 --> 00:21:37,310
Our colleagues at the CDC are experts
at advising people on that and they have

374
00:21:37,310 --> 00:21:42,670
resources available for both diagnosis
and advice on therapy as well if there

375
00:21:42,670 --> 00:21:44,110
should be an emerging case somewhere.

376
00:21:44,340 --> 00:21:48,550
And remember that also that of
those 12 cases, the majority have

377
00:21:48,550 --> 00:21:52,820
been imported cases through various
products brought into the U.

378
00:21:52,820 --> 00:21:52,940
S.

379
00:21:52,940 --> 00:21:53,870
or returned travellers.

380
00:21:54,149 --> 00:21:58,870
There was a case in 2019 related
to an aquarium that had fish which

381
00:21:58,870 --> 00:22:00,310
were imported from Southeast Asia.

382
00:22:00,719 --> 00:22:03,815
The, aquarium was positive for
Burkholderia pseudomallei, the

383
00:22:03,815 --> 00:22:07,825
water was, and that linked, uh,
was identical on genotyping to

384
00:22:07,825 --> 00:22:09,725
the isolate from the patient.

385
00:22:09,865 --> 00:22:14,684
You might be aware that there was the
tragedy of the four cases in the U.

386
00:22:14,684 --> 00:22:14,924
S.

387
00:22:14,925 --> 00:22:18,705
which was from imported
aromatherapy spray from India.

388
00:22:19,105 --> 00:22:22,465
Four cases, two fatal, and one of
those fatalities was in a child

389
00:22:22,465 --> 00:22:24,235
who was co infected with COVID.

390
00:22:24,535 --> 00:22:27,715
That was in four different states,
and it was an aromatherapy product

391
00:22:27,715 --> 00:22:29,395
imported, which was contaminated with B.

392
00:22:29,395 --> 00:22:29,915
pseudomallei.

393
00:22:29,934 --> 00:22:32,810
And again, the genotyping, we've
linked the isotopes from the

394
00:22:32,820 --> 00:22:35,320
patients to that aromatherapy spray.

395
00:22:35,985 --> 00:22:40,015
So these are the sort of scenarios, so
imported cases certainly happen, return

396
00:22:40,015 --> 00:22:44,995
travellers have melioid and now you have
it endemic in the US, so watch this space.

397
00:22:45,515 --> 00:22:46,485
Genevieve Martin: Okay, fantastic.

398
00:22:46,705 --> 00:22:50,165
I feel like I'm always learning so much
listening to you talk about melioid.

399
00:22:50,705 --> 00:22:53,714
Before we wrap up, are there
any other pearls of wisdom you

400
00:22:53,714 --> 00:22:55,135
have to share with the audience?

401
00:22:56,850 --> 00:23:00,039
Bart Currie: I guess there's a number
of things of interest and importance.

402
00:23:00,080 --> 00:23:03,559
One is our lack of understanding
still of how quickly it is

403
00:23:03,610 --> 00:23:04,949
spreading around the world.

404
00:23:05,279 --> 00:23:09,719
And so in other words, the unmasking
of long term endemicity versus, uh,

405
00:23:09,769 --> 00:23:13,399
spread such as I mentioned into the
Southern United States, and then what

406
00:23:13,399 --> 00:23:15,069
will happen over the next few decades.

407
00:23:15,580 --> 00:23:19,925
There is modeling suggesting that with
global warming, the organism will continue

408
00:23:19,925 --> 00:23:25,155
to proliferate potentially more rapidly
and in a more diverse geographic range

409
00:23:25,495 --> 00:23:28,784
because of the nature of the weather
that we're facing and the climate

410
00:23:28,874 --> 00:23:30,384
future that we're facing in the world.

411
00:23:30,995 --> 00:23:34,995
The other thing is, is that as an
opportunistic pathogen, which particularly

412
00:23:35,015 --> 00:23:39,810
is an issue for people living with
diabetes, the incredible increase in

413
00:23:39,810 --> 00:23:44,879
diabetes worldwide, particularly in lower
income countries and such as in Southeast

414
00:23:44,879 --> 00:23:50,420
Asia, parts of Southeast Asia, and in
the Americas as well, and also in Africa.

415
00:23:50,849 --> 00:23:53,589
It means that there's going to
be an enormous number of people

416
00:23:53,590 --> 00:23:57,550
who are susceptible to getting
unwell should they become infected.

417
00:23:58,080 --> 00:24:01,420
And I guess the final point is that
the positive side of things is that

418
00:24:02,060 --> 00:24:05,399
there's actually a vaccine on the
horizon, and there are three vaccines

419
00:24:05,399 --> 00:24:09,159
that are currently in active study,
and it's hoped that there will be, in

420
00:24:09,159 --> 00:24:14,580
the next 12 to 18 months, the first
ever in human trial of some of the

421
00:24:14,580 --> 00:24:16,389
first of these vaccines for mellidosis.

422
00:24:17,050 --> 00:24:18,110
Genevieve Martin: Okay, fantastic.

423
00:24:22,785 --> 00:24:25,335
Sara Dong: Thank you so much
to Genevieve, Catherine, and

424
00:24:25,335 --> 00:24:27,135
Bart for joining Febrile today.

425
00:24:27,135 --> 00:24:28,975
This was a really awesome episode.

426
00:24:29,005 --> 00:24:31,295
Don't forget to check out
the website, febrilepodcast.

427
00:24:31,325 --> 00:24:34,045
com, where you'll find the Consult
Notes, which are written complements

428
00:24:34,064 --> 00:24:37,864
of the show with links to references,
our library of ID infographics,

429
00:24:38,104 --> 00:24:39,675
and a link to our merch store.

430
00:24:40,094 --> 00:24:43,515
Febrile is produced with the support
of the ID Society of America.

431
00:24:43,685 --> 00:24:46,425
Audio editing and mixing is
provided by Bentley Brown.

432
00:24:46,905 --> 00:24:49,865
Please reach out if you have any
questions, suggestions for future shows,

433
00:24:49,895 --> 00:24:51,515
or want to be more involved with Febrile.

434
00:24:51,845 --> 00:24:54,145
Thanks for listening, stay safe,
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