AM Baciewicz

AO Soubani

B Dupont

BH Thompson

CA Kauffman

Christian Pohl

Elirehema Mfinanga

Fredrick Haraka

H Grysczyk

JF Regnard

JG Lee

JH Campbell

Joseph M. Vinetz

Khadija Said

KJ Hammerman

Klaus Reither

Levan Jugheli

M Kousha

PC Hopewell

S Kawamura

TJ Walsh

PLoS Neglected Tropical Diseases

English

PubMed

Crossref

Pulmonary Aspergilloma: A Treatment Challenge in Sub-Saharan Africa

Pohl, Christian

Jugheli, Levan

Haraka, Fredrick

Mfinanga, Elirehema

Said, Khadija

Reither, Klaus

edoc

SymposiumPulmonary Aspergilloma: A Treatment Challenge in Sub-Saharan AfricaChristian Pohl1,2,3*, Levan Jugheli1,2,3, Fredrick Haraka1, Elirehema Mfinanga1, Khadija Said1,Klaus Reither1,2,31 Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, United Republic of Tanzania, 2 Swiss Tropical and Public Health Institute, Basel,Switzerland, 3University of Basel, Basel, SwitzerlandPresentation of CaseIn April 2011, a 68-year-old man pre-sented himself at our research clinic in ruralTanzania with a three-month persistentproductive cough, chest pain, night sweats,and recurrent nonmassive haemoptysis. Hedenied fever, night sweats, weight loss, andany recent contact with a known tuberculo-sis case. A prior treatment with a broad-spectrum antibiotic had not been successful.The patient reported having been treatedfor tuberculosis, diagnosed by sputum smearten years ago. On examination he wasafebrile, in a reduced general condition witha body mass index of 17.1 kg/m2. Otherfindings were bilateral reduced breathsounds and mild clubbing. Testing forHIV with two rapid tests (SD Bioline HIV1/2 3.0 and Determine HIV-1/2) wasnegative. Posteroanterior chest radiographyin an erect position showed a cavity of60 mm673 mm diameter in the right upperlobe containing an intracavitary focal massof 47 mm631 mm diameter with adjacentmoon-shaped radiolucency (Figure 1). Asecond radiography in a supine positionshowed a changed position of this focal mass(Figure 2). A chest x-ray of the previous TBepisode was not available for comparison.Smear microscopy of early morning andspot sputum after Ziehl-Neelsen stain wasnegative for acid-fast bacilli. A nucleic acidamplification test (Xpert MTB/RIF) did notdetect Mycobacterium tuberculosis. Both theearly morning and spot sputum sampleswere subsequently cultured on solid (Lo¨w-enstein Jensen) and in liquid (MGIT) media,neither of which showed mycobacterialgrowth after eight and six weeks, respective-ly. In order to isolate Aspergillus, a sabourauddextrose agar was inoculated directly withsputum, but only Enterobacter cloacae could befound. Due to lack of facilities, neither anELISA for IgG antibodies to Aspergillus noran Aspergillus precipitin test could beperformed.Based on radiographies, a diagnosis ofsingle pulmonary aspergilloma was estab-lished, but we could not exclude that thesymptoms were caused by tuberculosisreactivation or reinfection. With negativesputum smears, chest radiography findingsconsistent with tuberculosis, and a lack ofresponse to a trial broad-spectrum antimi-crobial agent, our patient fulfilled theWHO criteria for sputum smear–negativetuberculosis. Without options for surgicaltreatment of pulmonary aspergilloma, wewere now faced with the decision of eitherstarting medication for pulmonary asper-gilloma or sending the patient for tuber-culosis treatment. Considering unavailabil-ity of sputum culture results at this pointand our setting with high prevalence oftuberculosis, we presented the case to theNational Tuberculosis and Leprosy Pro-gram (NTLP) which initiated six-monthstandard tuberculosis treatment accordingto national guidelines, which impliesprescription of rifampin, isoniazid, etham-butol, and pyrazinamide for two months,followed by rifampin and isoniazid for fourmonths. After six months of antitubercu-losis therapy, the patient was still in areduced condition, complaining aboutproductive cough and chest pain, but nohaemoptysis or night sweats. His bodymass index had increased to 19.2 kg/m2.Radiographies, however, did not show anyimprovement. Because of the persistentsymptomology, the patient was subse-quently started on antifungal treatmentwith itraconazole 200 mg daily for sixmonths. At the end of this period, thetreatment was extended for another sixmonths because the patient had reportedthat the dispensary had not been able toprovide him with medication continuouslyand therefore he had not been able to takemedication for the last three months oftreatment. At the last follow-up in October2012 we noticed a clinical improvement ofthe chest pain and no productive coughdespite a follow-up radiography not show-ing any changes.Case DiscussionPulmonary AspergillomaSince the common term mycetoma appliesaccurately to soft tissue infections, it is moreprecise to use pulmonary aspergilloma todescribe an intracavitary fungal mycelialgrowth in the lung. Pulmonary aspergillomacaused by A. fumigatus is the most widespreadof the noninvasive forms of pulmonaryaspergillosis and develops in preexisting lungcavities, most frequently tuberculous cavernsas seen in our case [1,2]. The aspergilloma(fungus ball) consists of masses of fungalmycelia, inflammatory cells, fibrin, mucus,and tissue debris [3]. The diagnosis is usuallymade clinically and radiographically withoutlung biopsy. Mild haemoptysis is commonlyreported as the main symptom, but mostpatients are asymptomatic. Bleeding isusually caused by local invasion and endo-toxic or mechanical irritation of exposedbronchial blood vessels. Symptoms likecough and dyspnoea are more likely relatedto underlying diseases, making a cleardiagnosis difficult [1]. As with our patient,50% of pulmonary aspergilloma sputumcultures for Aspergillus spp. are negative [2].Serum IgG antibodies to Aspergillus arepositive in most cases, but may be falsenegative in patients under corticosteroidtherapy or in rare cases of pulmonaryaspergilloma caused by other species thanCitation: Pohl C, Jugheli L, Haraka F, Mfinanga E, Said K, et al. (2013) Pulmonary Aspergilloma: A TreatmentChallenge in Sub-Saharan Africa. PLoS Negl Trop Dis 7(10): e2352. doi:10.1371/journal.pntd.0002352Editor: Joseph M. Vinetz, University of California San Diego School of Medicine, United States of AmericaPublished October 24, 2013Copyright:  2013 Pohl et al. This is an open-access article distributed under the terms of the CreativeCommons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,provided the original author and source are credited.Funding: The authors have indicated that no funding was received for this work.Competing Interests: The authors have declared that no competing interests exist.* E-mail: christian.pohl@unibas.chPLOS Neglected Tropical Diseases | www.plosntds.org 1 October 2013 | Volume 7 | Issue 10 | e2352A. fumigatus [1,3]. Chest radiographies showintracavitary mass (fungus ball) with an aircrescent (Monod sign) in about two-thirds ofthe cases [2,4]. This pattern is mostlylocalized in the upper lobe and can changeposition with gravity like in our radiogra-phies. Computed tomography can be usefulto detect smaller lesions that may not beapparent on conventional radiographies. Anincrease of wall thickness of the preexistingcavity suggests secondary infection [4]. Riskfactors for poor prognosis of pulmonaryaspergilloma include the severity of theunderlying lung disease, increase in size ornumber of lesions, and immunosuppression[1,3].Treatment DifficultiesThe first major decision is whethertherapy of the aspergilloma is required.With 10% of asymptomatic cases resolvingspontaneously, treatment usually becomesnecessary only when the patient developssymptoms [5]. Definitive treatment for anaspergilloma is surgery of the affected lung,which is indicated in case of recurrent orsevere haemoptysis. However, surgicalresection of the affected lung is associatedwith considerable morbidity and mortality.The mortality rates for surgical resection insymptomatic patients vary between 4–8%,the morbidity approaches 25% [6–8].These rates can be explained partly becauseFigure 1. Chest radiography showing a fungus ball with an air crescent in the right upper lobe.doi:10.1371/journal.pntd.0002352.g001PLOS Neglected Tropical Diseases | www.plosntds.org 2 October 2013 | Volume 7 | Issue 10 | e2352of the poor pulmonary function of manypatients with aspergilloma. Additionally, thedisease is rarely confined to the cavitarylesion seen on chest radiography and theadjacent lung and pleura are also involvedin the inflammatory response [7]. Lobecto-my, segmentectomy, pneumonectomy, andcavernostomy can be used as surgicalprocedures. The risks of compromisedpulmonary function, bronchopleural fistula,bleeding, and infection of the pleural spacemay outweigh the benefits, depending onthe individual patient. In inoperable pa-tients, primary treatment with antifungalagents seems to be an option. To date, thereis no consistent evidence about the appro-priate pharmacological treatment of singlepulmonary aspergilloma. The data guidingthe management of the disease are based onuncontrolled trials and case reports [9].Inhaled, intracavitary, and endobronchialinstillations of antifungal agents have showninconsistent success [1,10]. Among oralantifungals, itraconazole seems to be mosteffective due to its high tissue penetration,but only small studies have shown benefit sofar. Because of its slow effect, treatmentregimens have to last at least six months.The rates of symptomatic improvementvary from 61% to 71%, and those ofradiological improvement from 14% to23% [9–12]. However, due to the unpre-dictable natural history of aspergilloma, it isdifficult to attribute clinical improvement toa specific treatment. Parallel treatment withstandard tuberculosis medication should beavoided, because of the well-documentedinteraction between itraconazole and rifam-pin which may lead to therapeutic failure[13]. The role of newer antifungal azolessuch as voriconazole in the treatment ofaspergilloma has yet to be determined [1].The Presenting CaseThere is no epidemiological data onpulmonary aspergilloma in Tanzania andsub-Saharan Africa. However, the highburden of tuberculosis in these countriessuggests a considerable number of unre-ported cases. The case described hereshould not illustrate a new treatmentapproach but emphasize the limitationsand challenges in diagnosis and treatmentdue to resource limitations, the tuberculosisepidemic, and lack of consensus on thera-peutic approach. The means used in thiscase surpassed the resources of an averagerural setting, where we would have encoun-tered even more limitations. Our initialdiagnosis was purely based on the typicalradiological findings illustrated in Figure 1and Figure 2. Recurrent nonmassive hae-moptysis and other clinical symptoms at theFigure 2. Chest radiography in supine position showing a change of position of the fungus ball.doi:10.1371/journal.pntd.0002352.g002PLOS Neglected Tropical Diseases | www.plosntds.org 3 October 2013 | Volume 7 | Issue 10 | e2352first consultation were consistent withpulmonary aspergilloma and other pulmo-nary conditions, including tuberculosis.Unfortunately, we could not compareradiographies with the tuberculosis episodethat the patient had ten years before anddistinguish between new and old radiolog-ical manifestations. Consequently, our casefulfilled all criteria for a sputum smear–negative case according to national stan-dards [14] and the international standardsfor tuberculosis care in high epidemiccountries [15], and the NTLP decided tostart treatment despite of the unavailabilityof mycobacterial cultures at this point. If wehad attributed the symptoms purely topulmonary aspergilloma, surgical resectionwould have been the best treatment choice.Missing options of surgical treatment due tolack of resources and epidemiological con-cerns led to the decision to treat pharma-cologically, first for tuberculosis and subse-quently for pulmonary aspergilloma. Withtotal treatment duration of at least 12months, it was difficult to guarantee properadherence to both treatments. In our case,insufficient drug supply, as well as logisticaldifficulties in making the antifungal drugsavailable for the patient, led us to extend theantifungal therapy for another six months.It remains unclear if the treatment withtuberculostatica, antifungal medication, orthe natural history of pulmonary aspergil-loma caused the clinical improvement of thepatient, whose symptoms disappeared ex-cept residual chest pain. Retrospectively,although it was initially not possible toexclude a smear-negative tuberculosis case,treatment of pulmonary aspergillomashould have been given priority while TBtreatment should have been started only inthe case of positive cultures.The challenges in differential diagnosisand therapy of pulmonary aspergillomademonstrated in this case underline thenecessity for incorporating management ofthis frequently neglected TB-associateddisease into national TB treatment guide-lines in endemic countries.AcknowledgmentsWritten consent to publish history, findings,and images for educational purposes wasobtained from the patient. The authors wouldlike to acknowledge Dr. Mwinyi Kambi Salum,who is the District Tuberculosis and LeprosyCoordinator at Bagamoyo District Hospital, forhis collaboration in the management of thispatient.References1. Kousha M, Tadi R, Soubani A (2011) Pulmonaryaspergillosis: a clinical review. Eur Respir Rev 20:156–174. doi:10.1183/09059180.00001011.2. Kawamura S, Maesaki S, Tomono K, Tashiro T,Kohno S (2000) Clinical evaluation of 61 patientswith pulmonary aspergilloma. Internal Med 39:209–212.3. Soubani AO, Chandrasekar PH (2002) Theclinical spectrum of pulmonary aspergillosis.Chest 121: 1988–1999.4. Thompson BH, Stanford W, Galvin JR, KuriharaY (1995) Varied radiologic appearances of pulmo-nary aspergillosis. Radiographics 15: 1273–1284.5. Hammerman KJ, Christianson CS, Huntington I,Hurst GA, Zelman M, et al. (1973) Spontaneouslysis of aspergillomata. Chest 64: 697–699.6. Regnard JF, Icard P, Nicolosi M, Spagiarri L,Magdeleinat P, et al. (2000) Aspergilloma: a series of89 surgical cases. Ann Thorac Surg 69: 898–903.7. Kauffman CA (1996) Quandary about treatmentof aspergillomas persists. Lancet 347: 1640.8. Lee JG, Lee CY, Park IK, Kim DJ, Chang J, et al.(2009) Pulmonary aspergilloma: analysis of prog-nosis in relation to symptoms and treatment.J Thorac Cardiovasc Surg 138: 820–825.doi:10.1016/j.jtcvs.2009.01.019.9. Walsh TJ, Anaissie EJ, Denning DW, HerbrechtR, Kontoyiannis DP, et al. (2008) Treatment ofaspergillosis: clinical practice guidelines of theInfectious Diseases Society of America. ClinInfect Dis 46: 327–360. doi:10.1086/525258.10. Campbell JH, Winter JH, Richardson MD,Shankland GS, Banham SW (1991) Treatmentof pulmonary aspergilloma with itraconazole.Thorax 46: 839–841.11. Grysczyk H, De Roux A, Grassot A, Mauch H,Lode H (2002) [Antimycotic treatment of pulmo-nary aspergilloma in patients without neutrope-nia]. Dtsch Med Wochenschr 127: 492–496.doi:10.1055/s-2002-20940.12. Dupont B (1990) Itraconazole therapy in asper-gillosis: study in 49 patients. J Am Acad Dermatol23: 607–614.13. Baciewicz AM, Chrisman CR, Finch CK, SelfTH (2008) Update on rifampin and rifabutin druginteractions. Am J Med Sci 335: 126–136.doi:10.1097/MAJ.0b013e31814a586a.14. Ministry of Health and Social Welfare (2006)Manual of the National Tuberculosis and LeprosyProgramme in Tanzania. 5th edition. UnitedRepublic of Tanzania.15. Hopewell PC, Pai M, Maher D, Uplekar M,Raviglione MC (2006) International standards fortuberculosis care. Lancet Infect Dis 6: 710–725.doi:10.1016/S1473-3099(06)70628-4.Learning PointsN Pulmonary aspergilloma develops most frequently in residual tuberculouscavities.N Symptoms are often unspecific, making imaging the cornerstone of thediagnosis.N A mobile intracavitary mass with an air crescent are pathognomonic x-rayfindings.N In symptomatic patients, surgical resection is the treatment of choice.N Antifungal treatment can be considered as a therapeutic option, if surgery isnot possible.N Parallel treatment with rifampin and itraconazole should be avoided because ofdrug interactions.PLOS Neglected Tropical Diseases | www.plosntds.org 4 October 2013 | Volume 7 | Issue 10 | e2352

[Antimycotic treatment of pulmonary aspergilloma in patients without neutropenia].

Aspergilloma: a series of 89 surgical cases.

Clinical evaluation of 61 patients with pulmonary aspergilloma.

International standards for tuberculosis care.

Itraconazole therapy in aspergillosis: study in 49 patients.

Ministry of Health and Social Welfare

Pulmonary aspergilloma: analysis of prognosis in relation to symptoms and treatment.

Quandary about treatment of aspergillomas persists.

Soubani A

Spontaneous lysis of aspergillomata.

The clinical spectrum of pulmonary aspergillosis.

Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.

Treatment of pulmonary aspergilloma with itraconazole.

Update on rifampin and rifabutin drug interactions.

Varied radiologic appearances of pulmonary aspergillosis.

Pulmonary aspergilloma : a treatment challenge in sub-Saharan Africa

Directory of Open Access Journals

Pulmonary aspergilloma: a treatment challenge in sub-Saharan Africa.

Digital Library of the Tanzania Health Community

Symposium
Pulmonary Aspergilloma: A Treatment Challenge in Sub-
Saharan Africa
Christian Pohl
1,2,3*, Levan Jugheli
1,2,3, Fredrick Haraka
1, Elirehema Mfinanga
1, Khadija Said
1,
Klaus Reither
1,2,3
1Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, United Republic of Tanzania, 2Swiss Tropical and Public Health Institute, Basel,
Switzerland, 3University of Basel, Basel, Switzerland
Presentation of Case
In April 2011, a 68-year-old man pre-
sented himself at our research clinic in rural
Tanzania with a three-month persistent
productive cough, chest pain, night sweats,
and recurrent nonmassive haemoptysis. He
denied fever, night sweats, weight loss, and
any recent contact with a known tuberculo-
sis case. A prior treatment with a broad-
spectrum antibiotic had not been successful.
The patient reported having been treated
for tuberculosis, diagnosed by sputum smear
ten years ago. On examination he was
afebrile, in a reduced general condition with
a body mass index of 17.1 kg/m
2.O t h e r
findings were bilateral reduced breath
sounds and mild clubbing. Testing for
HIV with two rapid tests (SD Bioline HIV
1/2 3.0 and Determine HIV-1/2) was
negative. Posteroanterior chest radiography
in an erect position showed a cavity of
60 mm673 mm diameter in the right upper
lobe containing an intracavitary focal mass
of 47 mm631 mm diameter with adjacent
moon-shaped radiolucency (Figure 1). A
second radiography in a supine position
showed a changed position of this focal mass
(Figure 2). A chest x-ray of the previous TB
episode was not available for comparison.
Smear microscopy of early morning and
spot sputum after Ziehl-Neelsen stain was
negative for acid-fast bacilli. A nucleic acid
amplification test (Xpert MTB/RIF) did not
detect Mycobacterium tuberculosis.B o t ht h e
early morning and spot sputum samples
were subsequently cultured on solid (Lo ¨w-
enstein Jensen) and in liquid (MGIT) media,
neither of which showed mycobacterial
growth after eight and six weeks, respective-
ly. In order to isolate Aspergillus, a sabouraud
dextrose agar was inoculated directly with
sputum, but only Enterobacter cloacae could be
found. Due to lack of facilities, neither an
ELISA for IgG antibodies to Aspergillus nor
an Aspergillus precipitin test could be
performed.
Based on radiographies, a diagnosis of
single pulmonary aspergilloma was estab-
lished, but we could not exclude that the
symptoms were caused by tuberculosis
reactivation or reinfection. With negative
sputum smears, chest radiography findings
consistent with tuberculosis, and a lack of
response to a trial broad-spectrum antimi-
crobial agent, our patient fulfilled the
WHO criteria for sputum smear–negative
tuberculosis. Without options for surgical
treatment of pulmonary aspergilloma, we
were now faced with the decision of either
starting medication for pulmonary asper-
gilloma or sending the patient for tuber-
culosis treatment. Considering unavailabil-
ity of sputum culture results at this point
and our setting with high prevalence of
tuberculosis, we presented the case to the
National Tuberculosis and Leprosy Pro-
gram (NTLP) which initiated six-month
standard tuberculosis treatment according
to national guidelines, which implies
prescription of rifampin, isoniazid, etham-
butol, and pyrazinamide for two months,
followed by rifampin and isoniazid for four
months. After six months of antitubercu-
losis therapy, the patient was still in a
reduced condition, complaining about
productive cough and chest pain, but no
haemoptysis or night sweats. His body
mass index had increased to 19.2 kg/m
2.
Radiographies, however, did not show any
improvement. Because of the persistent
symptomology, the patient was subse-
quently started on antifungal treatment
with itraconazole 200 mg daily for six
months. At the end of this period, the
treatment was extended for another six
months because the patient had reported
that the dispensary had not been able to
provide him with medication continuously
and therefore he had not been able to take
medication for the last three months of
treatment. At the last follow-up in October
2012 we noticed a clinical improvement of
the chest pain and no productive cough
despite a follow-up radiography not show-
ing any changes.
Case Discussion
Pulmonary Aspergilloma
Since the common term mycetoma applies
accurately to soft tissue infections, it is more
precise to use pulmonary aspergilloma to
describe an intracavitary fungal mycelial
growth in the lung. Pulmonary aspergilloma
caused by A. fumigatus is the most widespread
of the noninvasive forms of pulmonary
aspergillosis and develops in preexisting lung
cavities,most frequently tuberculous caverns
as seen in our case [1,2]. The aspergilloma
(fungus ball) consists of masses of fungal
mycelia, inflammatory cells, fibrin, mucus,
and tissue debris [3]. The diagnosis is usually
made clinically and radiographically without
lung biopsy. Mild haemoptysis is commonly
reported as the main symptom, but most
patients are asymptomatic. Bleeding is
usually caused by local invasion and endo-
toxic or mechanical irritation of exposed
bronchial blood vessels. Symptoms like
cough and dyspnoea are more likely related
to underlying diseases, making a clear
diagnosis difficult [1]. As with our patient,
50% of pulmonary aspergilloma sputum
cultures for Aspergillus s p p .a r en e g a t i v e[ 2 ] .
Serum IgG antibodies to Aspergillus are
positive in most cases, but may be false
negative in patients under corticosteroid
therapy or in rare cases of pulmonary
aspergilloma caused by other species than
Citation: Pohl C, Jugheli L, Haraka F, Mfinanga E, Said K, et al. (2013) Pulmonary Aspergilloma: A Treatment
Challenge in Sub-Saharan Africa. PLoS Negl Trop Dis 7(10): e2352. doi:10.1371/journal.pntd.0002352
Editor: Joseph M. Vinetz, University of California San Diego School of Medicine, United States of America
Published October 24, 2013
Copyright:  2013 Pohl et al. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Funding: The authors have indicated that no funding was received for this work.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: christian.pohl@unibas.ch
PLOS Neglected Tropical Diseases | www.plosntds.org 1 October 2013 | Volume 7 | Issue 10 | e2352A. fumigatus [1,3]. Chest radiographies show
intracavitary mass (fungus ball) with an air
crescent (Monod sign) in about two-thirds of
the cases [2,4]. This pattern is mostly
localized in the upper lobe and can change
position with gravity like in our radiogra-
phies. Computed tomography can be useful
to detect smaller lesions that may not be
apparent on conventional radiographies. An
increase of wall thickness of the preexisting
cavity suggests secondary infection [4]. Risk
factors for poor prognosis of pulmonary
aspergilloma include the severity of the
underlying lung disease, increase in size or
number of lesions, and immunosuppression
[1,3].
Treatment Difficulties
The first major decision is whether
therapy of the aspergilloma is required.
With 10% of asymptomatic cases resolving
spontaneously, treatment usually becomes
necessary only when the patient develops
symptoms [5]. Definitive treatment for an
aspergilloma is surgery of the affected lung,
which is indicated in case of recurrent or
severe haemoptysis. However, surgical
resection of the affected lung is associated
with considerable morbidity and mortality.
The mortality rates for surgical resection in
symptomatic patients vary between 4–8%,
the morbidity approaches 25% [6–8].
These rates canbe explained partly because
Figure 1. Chest radiography showing a fungus ball with an air crescent in the right upper lobe.
doi:10.1371/journal.pntd.0002352.g001
PLOS Neglected Tropical Diseases | www.plosntds.org 2 October 2013 | Volume 7 | Issue 10 | e2352of the poor pulmonary function of many
patientswithaspergilloma.Additionally,the
disease is rarely confined to the cavitary
lesion seen on chest radiography and the
adjacent lung and pleura are also involved
in the inflammatory response [7]. Lobecto-
my, segmentectomy, pneumonectomy, and
cavernostomy can be used as surgical
procedures. The risks of compromised
pulmonary function, bronchopleural fistula,
bleeding, and infection of the pleural space
may outweigh the benefits, depending on
the individual patient. In inoperable pa-
tients, primary treatment with antifungal
agents seems to be an option. To date, there
is no consistent evidence about the appro-
priate pharmacological treatment of single
pulmonary aspergilloma. The data guiding
the management of the disease are based on
uncontrolled trials and case reports [9].
Inhaled, intracavitary, and endobronchial
instillations of antifungal agents have shown
inconsistent success [1,10]. Among oral
antifungals, itraconazole seems to be most
effective due to its high tissue penetration,
but only small studies have shown benefit so
far. Because of its slow effect, treatment
regimens have to last at least six months.
The rates of symptomatic improvement
vary from 61% to 71%, and those of
radiological improvement from 14% to
23% [9–12]. However, due to the unpre-
dictable natural history of aspergilloma, it is
difficult to attribute clinical improvement to
a specific treatment. Parallel treatment with
standard tuberculosis medication should be
avoided, because of the well-documented
interaction between itraconazole and rifam-
pin which may lead to therapeutic failure
[13]. The role of newer antifungal azoles
such as voriconazole in the treatment of
aspergilloma has yet to be determined [1].
The Presenting Case
There is no epidemiological data on
pulmonary aspergilloma in Tanzania and
sub-Saharan Africa. However, the high
burden of tuberculosis in these countries
suggests a considerable number of unre-
ported cases. The case described here
should not illustrate a new treatment
approach but emphasize the limitations
and challenges in diagnosis and treatment
due to resource limitations, the tuberculosis
epidemic, and lack of consensus on thera-
peutic approach. The means used in this
case surpassed the resources of an average
rural setting, where we would have encoun-
tered even more limitations. Our initial
diagnosis was purely based on the typical
radiological findings illustrated in Figure 1
and Figure 2. Recurrent nonmassive hae-
moptysis and other clinical symptoms at the
Figure 2. Chest radiography in supine position showing a change of position of the fungus ball.
doi:10.1371/journal.pntd.0002352.g002
PLOS Neglected Tropical Diseases | www.plosntds.org 3 October 2013 | Volume 7 | Issue 10 | e2352first consultation were consistent with
pulmonary aspergilloma and other pulmo-
nary conditions, including tuberculosis.
Unfortunately, we could not compare
radiographies with the tuberculosis episode
that the patient had ten years before and
distinguish between new and old radiolog-
ical manifestations. Consequently, our case
fulfilled all criteria for a sputum smear–
negative case according to national stan-
dards [14] and the international standards
for tuberculosis care in high epidemic
countries [15], and the NTLP decided to
start treatment despite of the unavailability
of mycobacterial cultures at this point. If we
had attributed the symptoms purely to
pulmonary aspergilloma, surgical resection
would have been the best treatment choice.
Missing options of surgical treatment due to
lack of resources and epidemiological con-
cerns led to the decision to treat pharma-
cologically, first for tuberculosis and subse-
quently for pulmonary aspergilloma. With
total treatment duration of at least 12
months, it was difficult to guarantee proper
adherence to both treatments. In our case,
insufficient drug supply, as well as logistical
difficulties in making the antifungal drugs
available for thepatient, led ustoextend the
antifungal therapy for another six months.
It remains unclear if the treatment with
tuberculostatica, antifungal medication, or
the natural history of pulmonary aspergil-
lomacausedtheclinicalimprovementofthe
patient, whose symptoms disappeared ex-
cept residual chest pain. Retrospectively,
although it was initially not possible to
exclude a smear-negative tuberculosis case,
treatment of pulmonary aspergilloma
should have been given priority while TB
treatment should have been started only in
the case of positive cultures.
The challenges in differential diagnosis
and therapy of pulmonary aspergilloma
demonstrated in this case underline the
necessity for incorporating management of
this frequently neglected TB-associated
disease into national TB treatment guide-
lines in endemic countries.
Acknowledgments
Written consent to publish history, findings,
and images for educational purposes was
obtained from the patient. The authors would
like to acknowledge Dr. Mwinyi Kambi Salum,
who is the District Tuberculosis and Leprosy
Coordinator at Bagamoyo District Hospital, for
his collaboration in the management of this
patient.
References
1. Kousha M, Tadi R, Soubani A (2011) Pulmonary
aspergillosis: a clinical review. Eur Respir Rev 20:
156–174. doi:10.1183/09059180.00001011.
2. Kawamura S, Maesaki S, Tomono K, Tashiro T,
Kohno S (2000) Clinical evaluation of 61 patients
with pulmonary aspergilloma. Internal Med 39:
209–212.
3. Soubani AO, Chandrasekar PH (2002) The
clinical spectrum of pulmonary aspergillosis.
Chest 121: 1988–1999.
4. Thompson BH, Stanford W, Galvin JR, Kurihara
Y (1995) Varied radiologic appearances of pulmo-
nary aspergillosis. Radiographics 15: 1273–1284.
5. Hammerman KJ, Christianson CS, Huntington I,
Hurst GA, Zelman M, et al. (1973) Spontaneous
lysis of aspergillomata. Chest 64: 697–699.
6. Regnard JF, Icard P, Nicolosi M, Spagiarri L,
MagdeleinatP,etal.(2000)Aspergilloma:a seriesof
89 surgical cases. Ann Thorac Surg 69: 898–903.
7. Kauffman CA (1996) Quandary about treatment
of aspergillomas persists. Lancet 347: 1640.
8. Lee JG, Lee CY, Park IK, Kim DJ, Chang J, et al.
(2009) Pulmonary aspergilloma: analysis of prog-
nosis in relation to symptoms and treatment.
J Thorac Cardiovasc Surg 138: 820–825.
doi:10.1016/j.jtcvs.2009.01.019.
9. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht
R, Kontoyiannis DP, et al. (2008) Treatment of
aspergillosis: clinical practice guidelines of the
Infectious Diseases Society of America. Clin
Infect Dis 46: 327–360. doi:10.1086/525258.
10. Campbell JH, Winter JH, Richardson MD,
Shankland GS, Banham SW (1991) Treatment
of pulmonary aspergilloma with itraconazole.
Thorax 46: 839–841.
11. Grysczyk H, De Roux A, Grassot A, Mauch H,
Lode H (2002) [Antimycotic treatment of pulmo-
nary aspergilloma in patients without neutrope-
nia]. Dtsch Med Wochenschr 127: 492–496.
doi:10.1055/s-2002-20940.
12. Dupont B (1990) Itraconazole therapy in asper-
gillosis: study in 49 patients. J Am Acad Dermatol
23: 607–614.
13. Baciewicz AM, Chrisman CR, Finch CK, Self
TH (2008) Update on rifampin and rifabutin drug
interactions. Am J Med Sci 335: 126–136.
doi:10.1097/MAJ.0b013e31814a586a.
14. Ministry of Health and Social Welfare (2006)
Manual of the National Tuberculosis and Leprosy
Programme in Tanzania. 5th edition. United
Republic of Tanzania.
15. Hopewell PC, Pai M, Maher D, Uplekar M,
Raviglione MC (2006) International standards for
tuberculosis care. Lancet Infect Dis 6: 710–725.
doi:10.1016/S1473-3099(06)70628-4.
Learning Points
N Pulmonary aspergilloma develops most frequently in residual tuberculous
cavities.
N Symptoms are often unspecific, making imaging the cornerstone of the
diagnosis.
N A mobile intracavitary mass with an air crescent are pathognomonic x-ray
findings.
N In symptomatic patients, surgical resection is the treatment of choice.
N Antifungal treatment can be considered as a therapeutic option, if surgery is
not possible.
N Parallel treatment with rifampin and itraconazole should be avoided because of
drug interactions.
PLOS Neglected Tropical Diseases | www.plosntds.org 4 October 2013 | Volume 7 | Issue 10 | e2352

MagdeleinatP,etal.(2000)Aspergilloma:a seriesof 89 surgical cases.

Pulmonary aspergilloma: a treatment challenge in sub-saharan Africa.

Pulmonary aspergilloma: a treatment challenge in sub-saharan Africa.

Abstract

Similar works

Full text

Available Versions

Crossref

edoc

Directory of Open Access Journals

Digital Library of the Tanzania Health Community