Fulminant tracheobronchial and pulmonary aspergillosis complicating imported Plasmodium falciparum malaria in an apparently immunocompetent woman.
ABSTRACT We describe an unusual case of fulminant tracheobronchial and pulmonary aspergillosis presenting as acute respiratory distress syndrome. The patient, who was apparently immunocompetent, was admitted with severe Plasmodium falciparum malaria but died from aspergillosis.
[show abstract] [hide abstract]
ABSTRACT: Management of severe malaria is an increasing problem worldwide. This paper reviews the pathophysiology and management documenting two years' experience of admissions of severe malaria to an ICU in a non-endemic area. Clinical and laboratory features of severe malaria were analysed for predictors of mortality Twenty-eight patients had clinical or laboratory features compatible with the WHO criteria for severe malaria and, despite treatment with intravenous quinine and supportive ICU care, mortality was 28.5% (8/28). The three pregnant patients died with 100% foetal mortality and the four paediatric patients survived. Of the non-survivors, 8/8 developed ARDS (defined by worst ALI score > 2.5), 7/8 developed shock requiring inotropic support and 7/8 developed acute renal failure requiring CVVHD. Admission haemoglobin, platelet count, parasite count, and lowest Glasgow Coma Score in the first 24 hours were shown not to be predictors of mortality.Anaesthesia and intensive care 04/1996; 24(2):217-23. · 1.28 Impact Factor
Article: Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis.[show abstract] [hide abstract]
ABSTRACT: Invasive aspergillosis is frequently a fatal disease in the setting of immunosuppression, including organ transplant recipients. The fungus usually affects lung parenchyma and may disseminate from there. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. This apparently new form of invasive disease is initially limited to the anastomosis site and large airways. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. In two patients subsequent disseminated aspergillosis occurred with a fatal outcome. In the two single-lung recipients, disease was limited to the transplanted side emphasizing the importance of abnormal local defense mechanisms in the airways of lung transplant recipients. Routine bronchoscopic examination of the airways is important in early detection of this complication. Oral therapy with the new, antifungal agent itraconazole was successful in five of the six patients, with fatal relapse in one. A classification of the various forms of saprophytic, allergic, and invasive forms of aspergillus tracheobronchitis, to include this new entity, is proposed.The American review of respiratory disease 10/1991; 144(3 Pt 1):552-6. · 10.19 Impact Factor
Article: Ulcerative and plaque-like tracheobronchitis due to infection with Aspergillus in patients with AIDS.[show abstract] [hide abstract]
ABSTRACT: Tracheobronchitis is an uncommon manifestation of infection due to Aspergillus species, occurring in < 7% of cases of pulmonary aspergillosis. At least 58 cases of invasive aspergillus tracheobronchitis have been described since 1962. We describe four patients with AIDS, all of whom were severely immunocompromised, who had ulcerative tracheobronchitis due to Aspergillus species demonstrated histologically. Three patients had received corticosteroids or were neutropenic at presentation. At bronchoscopy, three patients had some degree of diffuse tracheobronchitis, multiple ulcerative or "plaque-like" inflammatory lesions, and occasionally nodules involving the mainstem and segmental bronchi. The remaining patient had a single deep ulceration of the proximal trachea. Aspergillus was isolated from biopsy specimens from all four patients. There were varied degrees of invasion of the mucosa, submucosa, and cartilage on histological examination in three patients, one of whom had evidence of disseminated aspergillosis. Two patients subsequently developed pulmonary parenchymal disease due to Aspergillus. A review of aspergillus tracheobronchitis, including a discussion of airway disease in patients infected with human immunodeficiency virus, is presented.Clinical Infectious Diseases 09/1993; 17(3):344-52. · 9.15 Impact Factor
938Brief ReportsCID 2000;30 (June)
ever, Fernandez et al.  recently described a child with re-
current bacteremia despite appropriate repeated antibioticther-
apy who was cured only after the removal of the infected
catheter. In spite of the typically mild nature of this infection,
3 patients have died, 2 of whom were treatedwithinappropriate
antibiotic regimens .
Although infection with M. mesophilicum remains rare, it is
being reported with increasing frequency. Furthermore, even
though most previously reported cases have been nosocomial,
the increasing number of chronically immunocompromised pa-
tients treated as outpatients is likely to bring patients into con-
tact with the environmentalsiteswhereM.mesophilicumoccurs.
John W. Sanders,1James W. Martin,2Maria Hooke,3
and Jeffrey Hooke3
1Division of Infectious Disease, National Naval Medical Center,
Bethesda, Maryland, and
3Department of Pathology, Walter Reed Army Medical Center and
Healthcare System, Washington, D.C.
2Infectious Disease Service and the
1. Kaye KM, Macone A, Powel HK. Catheter infection caused by Methylo-
bacterium in immunocompromised hosts: report of three cases and review
of the literature. Clin Infect Dis 1992;14:1010–4.
2. Austin B, Goodfellow M. Pseudomonas mesophilica, a new species of pink
bacteria isolated from leaf surfaces. Int J Syst Bacteriol 1979;29:373–8.
3. Smith SM, Eng RHK, Forrester C. Pseudomonas mesophilica infections in
humans. J Clin Microbiol 1985;21:314–7.
4. Poirier A, Lapointe R, Claveau S, Joly J. Bacteremia caused by Pseudomonas
mesophilica. CMAJ 1988;139:411–2.
5. Liu JW, Wu JJ, Chen HM, Huang AH, Ko WC, Chuang YC. Methylobac-
terium mesophilicum synovitis in an alcoholic. Clin Infect Dis 1997;24:
6. Gilardi GL, Faur YC. Pseudomonas mesophilica and an unnamed taxon,
clinical isolates of pink-pigmented oxidative bacteria. J Clin Microbiol
7. Brown MA, Greene JN, Sandin RL, Hiemenz JW, Sinnott JT. Methylobac-
terium bacteremia after infusion of contaminated autologous bone mar-
row. Clin Infect Dis 1996;23:1191–2.
8. Gilchrist MJR, Kraft JA, Hammond JG,ConnellyBL,MyersMG.Detection
of Pseudomonas mesophilica as a source of nosocomial infections in a
bone marrow transplant unit. J Clin Microbiol 1986;23:1052–5.
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nonmotile bacterium as a cause of opportunistic infections. Arch Intern
10. Wallace PL, Hollis DG, Weaver RE, Moss CW. Biochemical and chemical
characterization of pink-pigmented oxidative bacteria. J Clin Microbiol
11. Brown WJ, Sautter RL, Crist AE. Susceptibility testing of clinical isolates
of Methylobacterium species. Antimicrob Agents Chemother 1992;36:
12. Hood DW, Dow CS, Green PN. DNA:DNA hybridization studies on the
pink-pigmented facultative methylotrophs. J Gen Microbiol 1987;133:
13. Fernandez M, Dreyer ZA, Hockenberry-Eaton M, Baker CJ. Methylobac-
terium mesophilicum as a cause of persistent bacteremia in a child with
lymphoma. Pediatr Infect Dis J 1997;16:1007–8.
14. Barzaga RA, Schoch PE, Cunha BA. Bacteremia due to CDC group II pink
coccoid bacilli. Clin Infect Dis 1993;16:735–6.
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ium species: an increasingly important opportunistic pathogen. Lab Med
16. Louria DB, Alture-Werber E, O’Hare D. An interesting microorganism
recovered from three patients with systemic disease. Am Rev Respir Dis
17. Lambert WC, Pathan AK, Imaeda T, Kaminski ZC, Reichman LB. Culture
of Vibrio extorquens from severe, chronic skin ulcers in a Puerto Rican
woman. J Am Acad Dermatol 1983;9:262–8.
18. Dewar JW, Wagner KR. Peritonitis due to Methylobacterium mesophilicum
complicating ambulatory peritoneal dialysis: British Columbia. Can Dis
19. Rutherford PC, Narkowicz JE, Wod CJ, Peel MM. Peritonitis caused by
Pseudomonas mesophilica in a patient undergoing continuous ambulatory
peritoneal dialysis. J Clin Microbiol 1988;26:2441–3.
20. Holton J, Miller R, Furst V, Malnick H. Isolation of Protomonas extorquens
(the “red phantom”) from a patient with AIDS. J Infect 1990;21:87–93.
21. Gould FK, Venning MC,FordM.Successfultreatmentwithchloramphenicol
of Pseudomonas mesophilica peritonitis not responding to aztreonam and
gentamicin. J Antimicrob Chemother 1990;26:458–9.
22. Egbert JE, Feder JM, Rapoza PA, Chandler JW, France TD. Keratitis as-
sociated with Pseudomonas mesophilica in a patient taking topical corti-
costeroids. Am J Ophthalmol 1990;110:445–6.
23. Strazzi SR, Baccard M, Puppin D, Plancke L, Morel P. Pseudomonas me-
sophilica cutaneous infection in an immunocompetent patient. Arch Der-
24. Zabrawski RJ, Ellis T, Canaday D. Methylobacterium spp. from a patient
with multiple sclerosis. Clin Microbiol Newsl 1997;19:150–2.
25. Truant AL, Gulati R, Giger O, Satishchandran V, Caya JG. Methylobacter-
ium bacteremia in AIDS. Clin Microbiol Infect 1998;4:112–3.
Fulminant Tracheobronchial and Pulmonary
Aspergillosis Complicating Imported Plasmodium
falciparum Malaria in an Apparently
We describe an unusual case of fulminant tracheobron-
chial and pulmonary aspergillosis presenting as acute res-
piratory distress syndrome. The patient, who was appar-
ently immunocompetent, was admitted with severe Plas-
modium falciparum malaria but died from aspergillosis.
Imported malaria is an increasing problem in many devel-
oped countries. In 1998, 996 cases of imported malaria were
recorded in Germany . The case fatality rate associated with
imported Plasmodium falciparum malaria varies from 0.6% to
3.8% and may be up to 28.5% for severe malaria, even when
Reprints or correspondence: Priv.-Doz. Dr. Med. Markus Ruhnke, Dept.
of Medicine, Charite Campus Virchow Klinikum, Augustenburger Platz 1,
13353 Berlin, Germany (email@example.com).
Clinical Infectious Diseases
? 2000 by the Infectious Diseases Society of America. All rights reserved.
by guest on July 14, 2011
CID 2000;30 (June)Brief Reports 939
with diffuse bilateral pulmonary infiltrates that resemble those asso-
ciated with acute respiratory distress syndrome.
Chest radiograph on day 5 after admission of a patient
treated in intensive care unit conditions . Poor outcome is
predicted by the occurrence of complications during Plasmo-
dium falciparum malaria, such as coma, hypoglycemia, and res-
piratory distress. Adult respiratory distress syndrome (ARDS)
has always had a fatal outcome . We describe an apparently
otherwise healthy woman who died of fulminant tracheobron-
chial and pulmonary aspergillosis under the aspect of ARDS
following P. falciparum malaria.
A 54-year-old woman was admitted to a district hospital
because of fever of unknown origin. The patient reported the
onset of fever 4 days after returning from a 2-week trip to
Kenya. Malaria prophylaxis was not taken. After 2 days of
the patient was admitted to the hospital. On presentation she
had a fever (temperature, 40?C), and examination revealedmild
hepatosplenomegaly and icterus; her condition was otherwise
stable and there were no pulmonary symptoms. No underlying
diseases (such as liver cirrhosis or malignancy) were reported,
other than hysterectomy for uterine myomatosis several years
before. Laboratory evaluation revealed parasitemia with P. fal-
ciparum (15% infected erythrocytes and a hematocrit of 46%),
a WBC count of 5400 cells/mL, a platelet count of 16,000 cells/
mL, a total bilirubin of 7.8 mg/dL (direct bilirubin, 7.1 mg/dL),
a prothrombin time of 60%, an aspartate aminotransferase
(AST) level of 262 U/L, a lactate dehydrogenase (LDH) level
of 1904 U/L, and a creatinine level of 2.9 mg/dL.
Therapy with quinine dihydrochloride plus doxycycline was
initiated. Within 24 h, the patient’s condition deteriorated
markedly because of altered mentalstatuswithsevereconfusion
and delirium, suggestive of cerebral malaria. Midazolam was
started for sedation. She became oliguric, her creatinine level
increased to 4.7 mg/dL, and she underwent dialysis.
The patient was transferred to our intensive care unit. She
presented in a comatose state and was intubated for artificial
ventilation. Clindamycin was added as an antimalarial agent.
Findings of a chest radiograph were normal, but a CT scan of
the brain revealed cerebral edema, which was treated surgically
by intraventricular drainage. Exchange transfusion was per-
formed, and continuous hemofiltration was started 12 h later.
Parasitemia was undetectable after 48 h, but the patient de-
veloped lactic acidosis with progressive deterioration of circu-
latory and pulmonary function as well as liver failure (bilirubin
level, 27.5 mg/dL, AST level, 1550 mg/dL, and LDH level,7270
mg/dL). Chest radiograph on day 5 showed pulmonary infil-
trates (figure 1), and bronchoscopy revealed marked hemor-
rhage and necrosis in the trachea, and the bronchial tree and
trachea were covered with a layer of white mucus. A culture
of a bronchoalveolar lavage specimen yielded Aspergillus fu-
migatus (104cfu/mL) and Enterobacter species. Aspergillus an-
tigen testing from serum was strongly positive (PlateliaELISA;
Sanofi Pasteur, Freiburg, Germany; titer for detection of gal-
actomannan antigen was 5.5 (a titer of 1.5 is considered pos-
itive). Amphotericin B was started, but on the 6th day after
admission to our institution the patient died of ARDS and
multiorgan failure with shock and lactic acidosis. Autopsy re-
vealed invasive pulmonary aspergillosis, and Aspergillus trach-
eobronchitis with macroscopically confluent growth of mold in
the trachea and bronchi were found.
Aspergillus tracheobronchitis has been described predomi-
nantly in patients with AIDS and in lung transplant recipients
[3, 4]. Reports in immunocompetent patients are rare, and the
pathogenesis of this disease in these patients who are not neu-
tropenic or receiving corticosteroids is not well understood
[5–7]. To date, the association of Aspergillus tracheobronchitis
with tropical diseases, such as malaria, has not been described.
In our patient, the clinical presentation suggested the devel-
opment of ARDS caused by severe malaria rather than pul-
monary aspergillosis. The patient had a fulminant course of
disease and died within 3 days of the onset of signs on the chest
radiograph. It is clear that the fatal outcome is strongly influ-
enced by the presentation of cerebral malaria. The diagnosis
could not be made on clinical grounds, but bronchoscopy
showed the typical picture of pseudomembranous tracheo-
bronchitis and a tracheobronchial tree covered with a white
layer of mucus, as described elsewhere .
From this single case, it cannot be concluded that ARDS
with severe malaria is caused bytracheobronchialorpulmonary
aspergillosis. However, the growing number of reports about
Aspergillus tracheobronchitis in apparently immunocompetent
patients should prompt further investigation to understand the
pathogenesis of the disease.
by guest on July 14, 2011
940Brief Reports CID 2000;30 (June)
Markus Ruhnke,1Elisabeth Eichenauer,2Julia Searle,2
and Frank Lippek3
1Department of Medicine, Division of Hematology and Oncology,
3Division of Intensive Care and Nephrology,
Charite ´ Campus Virchow Klinikum, Berlin, Germany
3Institute of Pathology,
1. Robert Koch–Institut. Jahresstatistik ausgewa ¨hltermeldepflichtigerInfektion-
skrankheiten 1998. Epidemiologisches Bulletin [serial online] 1999;14:93-5.
Available at http://www.rki.de/INFEKT/EPIBULL/EPI.htm. Accessed 7
2. Blumberg L, Lee RP, Lipman J, Beards S. Predictors of mortality in severe
malaria: a two year experience in a non-endemic area. Anaesthesia and
Intensive Care 1996;24:217–23.
3. Kramer MR, Denning DW, Marshall SE, et al. Ulcerative tracheobronchitis
after lung transplantation: a new form of invasive aspergillosis. Am Rev
Respir Dis 1991;144:552–6.
4. Kemper CA, Hostetler JS, Follansbee SE, et al. Ulcerative and plaque-like
tracheobronchitis due to infection with Aspergillus in patients with AIDS.
Clin Infect Dis 1993;17:344–52.
5. Cooper JA, Weinbaum DL, Aldrich TK, Mandell GL. Invasive aspergillosis
of the lung and pericardium in a nonimmunocompromised 33-year-old
man. Am J Med 1981;71:903–7.
6. Karam GH, Griffin FM Jr. Invasive pulmonary aspergillosis in nonimmu-
nocompromised, nonneutropenic hosts. Rev Infect Dis 1986;8:357–63.
7. Sidorov J. Aspergillosis in a healthy host [letter]. South Med J 1988;81:679.
8. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26:781–803.
Fatal Invasive Aspergillosis Complicating Severe
Plasmodium falciparum Malaria
We report the first 2 cases of fatal invasive aspergillosis
complicating severe malaria. In 2 nonimmune European
adults without underlying disease, death was directly as-
cribable to invasive aspergillosis. We believe that transient
malaria-induced immunosuppression allowed massive
growth and overwhelming dissemination of preexisting
We report the first 2 cases of invasive aspergillosis compli-
cating severe Plasmodium falciparum malaria and discuss the
pathogenic mechanisms underlying this association. We
searched MEDLINE for studies published from 1968 through
1999 that mention “malaria,” “falciparum” or “plasmodium”
and “aspergillosis” or “A. fumigatus.”
From 1987 through 1998, 205 patients were admitted to our
intensive care unit (ICU) for imported falciparum malaria. The
overall mortality rate was 7.3% (15 deaths). In 2 nonimmune
European patients, death was directly ascribable to invasive
Patient 1, a 40-year-old man, was hospitalized in China in
1987 because of fever and jaundice and received a 3-day course
of iv corticosteroids for suspected hepatitis. Three days later,
because of impaired consciousness(Glasgowcomascore[GCS],
12), the decision was made to repatriate the patient. When he
arrived in France 2 days later, he was referred to our ICU
because of severe malaria with 19% parasitemia, rousablecoma
(GCS, 11), acute renal failure, and disseminated intravascular
coagulation. A chest radiograph showed an alveolar infiltrate
in the right upper lobe. The patient’s conditionimprovedslowly
Reprints or correspondence: Docteur Fabrice Bruneel, Clinique de Re ´an-
imation des Maladies Infectieuses (Pr REGNIER), Ho ˆpital Bichat-Claude
Bernard, 46 Rue Henri Huchard, 75018 Paris, France (fabrice.bruneel
Clinical Infectious Diseases
? 2000 by the Infectious Diseases Society of America. All rights reserved.
with quinine infusion, antibiotics, mechanical ventilation, and
hemodialysis. The parasitemia abated within 72 h, and neu-
rologic disorders and pneumonia resolved. On day 12, he rap-
idly developed unrousable coma (GCS, 5), flaccid tetraplegia,
and shock. A cerebral CT scan showed hemorrhagic infarction
of the cerebellum and brain. The patient died 4 days later in
a deep coma. Autopsy revealed invasive aspergillosis with ul-
cerated mitral endocarditis and fungal abscesses in the myo-
cardium and lungs (figure 1). The biopsy of a cutaneous lesion
yielded Aspergillus fumigatus.
In 1997, patient 2, a 32-year-old man, returned from a trip
to Gabon. He had been given oral cefuroxime by his physician
for suspected acutesinusitis.Fourdayslaterhewashospitalized
through the emergency room of our hospital because of fever
and jaundice. P. falciparum parasitemia was 48%. A quinine
infusion was started and the patient was referred to our ICU.
Over the following 24 h his condition worsened rapidly, and
acidosis, acute renal failure, and acute respiratory distress syn-
drome. Upon intubation of the patient, macroscopic evidence
of esophageal mycosis was noted. Specific tests excluded HIV
infection or primary infection. Despite supportive careandpar-
asite clearance within 72 h, his neurologic status failed to im-
prove. On day 3, a bronchoalveolar lavage yielded Aspergillus
nidulans and Candida albicans. Intravenous amphotericin B (1
mg/kg/d) was started. On day 5, a tracheal aspirate yielded
Pseudomonas aeruginosa, Staphylococcus aureus, and A. fumi-
gatus. Aztreonam and ciprofloxacin therapy was instituted and
amphotericin was discontinued, as fungal presence wasthought
to be a colonization. On day 11, cardiac arrest occurred and
resuscitation efforts failed. Autopsy disclosed disseminated as-
pergillosis with cerebral and pulmonary fungal abscesses.
Fungal infection is thought to be uncommon during severe
malaria [1, 2]. In our cases, coincidental occurrence of asper-
gillosis and malaria is very unlikely because invasive aspergil-
losis is extremely rare in healthy patients . The absence of a
coincident aspergillosis outbreak in our ICU and the short time
from admission to aspergillosis onset militate against ICU-
by guest on July 14, 2011