Thursday, February 16, 2017

PRO/EDR> Buruli ulcer - Sao Tome and Principe (03): A. fumigatus, PCR, bone biopsy, RFI

BURULI ULCER - SAO TOMA AND PRINCIPE (03): ASPERGILLUS FUMIGATUS, PCR,
BONE BIOPSY, REQUEST FOR INFORMATION
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Date: Wed 8 Feb 2017
From: Raquel Tavares <raquelmrtavares@gmail.com> [edited]


[Re: ProMED-mail posts Buruli ulcer - Sao Tome and Principe
http://promedmail.org/post/20170208.4824961 and
http://promedmail.org/post/20170210.4830051]
----------------------------------------------------------------------
In March 2016 we started following a patient from Sao Tome with severe
leg ulcer, complicated with bacterial infection and extension to bone.
In December 2016, an _Aspergillus fumigatus_ DNA was found in a bone
biopsy.

The patient has improved since, with anti-fungal therapy (first with
itraconazole and in the last 2 months changed to voriconazole). I
think this is a possible etiology.

It was a very difficult diagnosis, because normal fungal cultures were
negative. We also did DNA and culture for _Mycobacterium ulcerans_ and
it was negative.

--
Raquel Tavares, MD
Infectious Diseases Specialist
Hospital Beatriz Angelo
Loures
Portugal
<raquelmrtavares@gmail.com>

[Dr Tavares sent in additional information on this patient:

- Male, 39 years of age, born at Democratic [Republic of Sao Tome and
Principe] (STP), with a 2-year history of an extensive ulcer on the
anterolateral side of the left leg, starting as nodules that ulcerated
and coalesced, and associated with severe hypochromic microcytic
anemia and loss of 24 kg, living in Portugal since March 2016, working
as a taxi driver.
- History of chronic hepatitis B infection
- In STP, went daily to his farm, bathing daily in a river or small
lakes.
- No known allergies to any drugs.
- No treatment to Buruli ulcer
- In STP: November 2015: ampicillin 2 weeks
- In Portugal: March 2016: amoxicillin, clarithromycin, metronidazole,
pantoprazol for 2 weeks for _H. pylori_ infection; April 2016:
ciprofloxacin for 1 week, piperacillin/tazobactam for 1 week;
ivermectin 18 mg oral once for ascariasis and strongyloidiasis;
June-July 2016: empiric treatment with itraconazole for 6 weeks;
October-November: itraconazole and vancomycin for 42 days; and since
December 2016: voriconazole.
- In August 2016: deep venous thrombosis complicated by pulmonary
thromboembolism
- No contaminated traumatic, burn, or surgical wounds, intravenous
catheters, or use of occlusive dressings, adhesive tape, and plaster
casts
- Negative culture and DNA test (PCR) of ulcer tissue for
_Mycobacterium ulcerans_
- Histology of ulcer tissue, April 2016: "stasis dermis, fibrosis area
and inflammatory foreign body reaction and necrosis, PAS [Periodic
Acid-Schiff], and Grocott [for fungi], and Ziehl-Neelsen [for
mycobacteria] stains were negative."

The patient from STP described above with a leg ulcer had a positive
PCR for _Aspergillus fumigatus_ in a bone biopsy and a presumptive
diagnosis of primary cutaneous aspergillosis in an immunocompetent
patient.

_Aspergillus fumigatus_ represents a major cause of morbidity and
mortality in immunocompromised patients. In these patients, cutaneous
aspergillosis is usually a manifestation of disseminated _Aspergillus_
infection. Primary cutaneous disease is uncommon and can develop at
the sites of contaminated traumatic, burn, and surgical wounds,
intravenous catheters, and use of occlusive dressings, adhesive tape,
and plaster casts
(<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC105285/>), which this
patient did not have.

Transmission of _M. ulcerans_ is thought to occur from contact with
_M. ulcerans_-contaminated water, soil or vegetation, which the
patient could have had when he bathed daily in a river or lakes in
STP. Secondary, usually bacterial, infection is known to complicate
Buruli ulcer, which the patient also apparently had
(<http://www.who.int/buruli/information/diagnosis/en/index6.html>).
The histology of the patient's ulcer biopsy was consistent with that
of Buruli ulcer
(<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000137/>), but
staining of tissue was negative for mycobacteria and the culture and
PCR for _Mycobacterium ulcerans_ were negative. However, the
sensitivity for _M. ulcerans_ culture is reported to be only 50
percent for Buruli ulcer tissue, and only 20 percent for bone
(<http://www.who.int/buruli/information/diagnosis/en/index8.html>);
sensitivity of staining for mycobacteria in Buruli ulcer is only 40-60
percent
(<http://www.who.int/buruli/information/diagnosis/en/index8.html> and
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1233911/>). However, the
sensitivity of _M. ulcerans_ PCR is reported to be greater than 90
percent for ulcer tissue
(<http://www.who.int/buruli/information/diagnosis/en/index8.html> and
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1233911/>).

The patient's diagnosis of primary cutaneous aspergillosis is based
solely on a positive PCR in bone for _Aspergillus_. Considering that
_Aspergillus_ is a ubiquitous organism, a positive PCR for this
organism may very well be due to minute contamination of the bone
specimen with fungal DNA. Cutaneous aspergillosis, if the diagnosis is
correct, may be secondary to whatever caused the initial leg ulcer.

In any case, what does this patient's diagnosis, if correct, imply
about the diagnoses in the other 1094 cases of ulcer disease that have
been reported in STP since October 2016? It would be very unusual if
any of the others in STP has cutaneous aspergillosis, unless, as
ProMED-mail Mod.MPP suggested, others have used some medication
contaminated with _Aspergillus_ that was applied to their ulcers.

Nevertheless, more information on this outbreak in Sao Tome is needed
-- a clear clinical description of the skin lesions, the results of
tests used to confirm a diagnosis of Buruli ulcer, that is, polymerase
chain reaction (PCR), acid-fast staining, histopathology, and culture,
and evaluation for other conditions that could cause cutaneous ulcer
disease in this population.

A HealthMap/ProMED-mail map can be accessed at:
<http://healthmap.org/promed/p/63>. - Mod.ML]

[See Also:
Buruli ulcer - São Tomé and Príncipe (02): comment, RFI
http://promedmail.org/post/20170210.4830051
Buruli ulcer - São Tomé and Príncipe
http://promedmail.org/post/20170208.4824961]
.................................................mpp/ml/mj/jh
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