Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: a case report and review of literature.

2.1 MB·English

by  Sudjaritruk, Tavitiya

Sudjaritruketal.BMCInfectiousDiseases2012,12:28
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CASE REPORT Open Access
Immune reconstitution inflammatory syndrome
from Penicillium marneffei in an HIV-infected
child: a case report and review of literature
Tavitiya Sudjaritruk1, Thira Sirisanthana2 and Virat Sirisanthana1,2*
Abstract
Backgrounds: Disseminated Penicillium marneffei infection is one of the most common HIV-related opportunistic
infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to
antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected
child who developed an unmasking type of IRIS caused by disseminated P. marneffei infection after ART initiation.
Case presentation: A 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated
oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and
multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4+ cell count was 7.2%
or 39 cells/mm3. On admission, her repeated CD4+ cell count was 11% or 51 cells/mm3 and her plasma HIV-RNA
level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic
infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic
acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular,
round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture,
and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous
amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without
evidence of recurrence of disease.
Conclusions: IRIS from P. marneffei in HIV-infected people is rare. Appropriate recognition and properly treatment
is important for a good prognosis.
Background secondary prophylaxis with itraconazole are very effec-
Penicillium marneffei is a dimorphic fungus which can tive regimens [8]. Patients who do not receive timely
cause a fatal systemic mycosis in human immunodefi- and appropriate antifungal treatment have poor out-
ciency virus (HIV)-infected patients. This organism is comes [5]. Immune reconstitution inflammatory syn-
endemic in tropical Asia, especially Thailand, northeast- drome (IRIS) is a complication related to antiretroviral
ern India, China, Hong Kong, Vietnam, and Taiwan therapy (ART)-induced immune restoration. IRIS mani-
[1-6]. Disseminated P. marneffei infection is one of the fests as a paradoxical exacerbation of previously treated
most common HIV-related opportunistic infections in opportunistic infections (paradoxical or worsening IRIS)
northern Thailand [5]. The typical manifestations of P. or as an unmasking of subclinical, untreated infections
marneffei infection in HIV-infected individuals include (unmasking IRIS) [9-12]. It is a consequence of exagger-
fever, anemia, weight loss, skin lesions, generalized lym- ated activation of the immune response against infec-
phadenopathy, and hepatomegaly [5,7]. The primary tious organisms [13,14]. In this report, we present a case
treatment with amphotericin B and itraconazole and of HIV-infected child with IRIS from disseminated
P. marneffei infection.
*Correspondence:[email protected]
1DivisionofInfectiousDiseases,DepartmentofPediatrics,Facultyof
Medicine,ChiangMaiUniversity,50200ChiangMai,Thailand
Fulllistofauthorinformationisavailableattheendofthearticle
©2012Sudjaritruketal;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
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Case presentation Table 1Laboratory resultson the dayofadmission
A 14-year-old Thai girl presented at a provincial hospi- Laboratoryinvestigations Results Normalvalue
tal with fever, oral ulcers, disseminated papular lesions Hemoglobin(g/dL) 8.0 10.0-15.0
and multiple joint pain for 4 weeks. Twelve weeks
Hematocrit(%) 23.9 36.0-45.0
before this admission, she was diagnosed as a case of
Whitebloodcount(×109/L) 7.6 5-10
perinatal HIV infection after presenting with dissemi-
Absoluteneutrophilcount 5.9 2.0-8.0
nated herpes zoster infection and Pneumocystis jirovecii
pneumonia (PJP). At that time, her CD4+ cell count was Absolutelymphocytecount 0.5 0.7-4.4
7.2% or 39 cells/mm3. Plasma HIV-RNA level was not Platelet(×109/L) 498 100-400
obtained. She was started on GPOvirS30® (a fixed drug SGOT(U/L) 21 <35
combination of stavudine 30 mg, lamivudine 150 mg SGPT(U/L) 10 <41
and nevirapine 200 mg) 1 tablet twice daily and PJP pro- LDH(U/L) 161 120-450
phylaxis with trimethoprim-sulfamethoxazole. Eight ESR(mm/hr) >140 0-10
weeks after starting ART she developed fever, multiple
CRP(mg/L) 80.7 0-5.0
oral ulcers, disseminated papular lesions over the face,
Note:SGOTindicatesSerumglutamicoxaloacetictransaminase;SGPT,Serum
body, and extremities, and severe pain in many joints. glutamicpyruvictransaminase;LDH,Lactatedehydrogenase;ESR,Erythrocyte
The symptoms did not respond to many kinds of oral sedimentationrate;CRP,C-reactiveprotein
antibiotics and she was referred to Chiang Mai Univer-
sity (CMU) Hospital. neutrophilic infiltration in the upper and reticular der-
Upon admission to CMU Hospital, the physical exam- mis. Tissue sections from skin biopsy stained with
ination revealed high-grade fever. Multiple painful ulcer- hematoxylin and eosin (H&E), periodic acid-Schiff
ated lesions were found on the lip and oral mucosa. (PAS), and Grocott methenamine silver (GMS) stain
Generalized non-pruritic erythrematous papules and revealed numerous intracellular and extracellular, round
nodules with central umbilication were found over the to oval, elongated, thin-walled yeast cells with central
face, body, and extremities (Figure 1). Marked swelling, septation (Figure 3). No organism was observed in the
warmth, and tenderness of many joints, including right bone marrow aspirate specimen. The hemoculture, bone
shoulder, wrist, metacarpophalangeal, knee, and ankle marrow culture, and skin culture revealed no evidence
joints were also noticed. Neither lymphadenopathy nor of P. marneffei or other fungus. Blood was also sent for
hepatosplenomegaly were found. Her laboratory results mycobacterial culture with negative results. Serum cryp-
are shown in Table 1. CD4+ cell count was 11% or 51 tococcal antigen was negative. The diagnosis of dissemi-
cells/mm3. Plasma HIV-RNA level was < 50 copies/mL. nated P. marneffei infection from unmasking IRIS was
Chest roentgenogram was normal. Roentgenograms of made.
both wrists and ankles showed multiple round radiolu- The patient was treated with intravenous amphotericin
cent defects of the bones (Figure 2). Skin biopsy showed B at a dosage of 0.7 mg/kg for 2 weeks along with para-
necrotizing histiocytic granuloma formation with cetamol and ibuprofen, followed by oral itraconazole at
a dosage of 5 mg/kg twice daily orally. She responded
well to treatment. Her fever, skin lesions, and joints
pain gradually resolved. She was discharged with a plan
to complete a 10-week course of oral itraconazole ther-
apy followed by the maintenance therapy with oral itra-
conazole at a reduced dosage of 5 mg/kg daily. Her skin
lesions and joints pain resolved after 4 weeks of antifun-
gal treatment, and itraconazole was discontinued after 4
months of maintenance treatment. After 1 year of ther-
apy, she had gained 4 kg weight without recurrence of
P. marneffei infection. Her repeated CD4+ cell count
had risen to 21.1% or 269 cells/mm3. Her plasma HIV
RNA level was undetectable (< 50 copies/mL).
Conclusions
Figure 1 Cutaneous lesions initially presented as small We reported a case of HIV-infected child who devel-
papules,enlargedtolargerpapuleswithcentralnecrotic oped an unmasking IRIS caused by disseminated P.
umbilications.Theywerepredominantlyfoundonthefaceand marneffei infection 8 weeks after ART initiation. After
extremities.
treatment with antifungal therapy, amphotericin B
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Figure2Radiologicevidencesofosteolyticlesionsoftheextremities.a.Multipleosteolyticlesionsarenotedalongthemetaphyseallineof
the2ndto4thmetacarpophalangealjoints(arrow)withpericarticularosteopeniaofthewristandmetacarpophalangealjoints.Largeosteolytic
lesionsarealsonotedatrightdistalradiusandulnar(arrows).Nowideningofbothwristjointspaces.Sharpbonycortexofbothradiusand
ulnar.b.Multipleosteolyticlesionsarenotedatrightcalcaneous(arrow).Nowideningofbothanklejointspaces.Sharpbonycortexofboth
tibiaandfibula.
followed by itraconazole, she had fully recovery without 19% of IRIS in advanced stage Thai HIV-infected chil-
evidence of recurrence. dren with the median onset of 4 weeks (range, 2-31)
IRIS is a manifestation of vigorous immune recovery after ART commencement. The three major causative
which usually occurs within a few weeks to months pathogens were mycobacterial spp. (43.8%), both Myco-
after potent ART initiation in advanced stage HIV- bacterium tuberculosis (TB) and non-tuberculous myco-
infected patients. This inflammatory reaction is directed bacterium, varicella zoster virus (VZV) (21.9%), and
against pathogens causing latent or subclinical infection. herpes simplex virus (HSV) (21.9%) [17]. Recently,
The majority of patients present with unusual manifes- Smith et al. reported an incidence of 21% of IRIS in
tations of opportunistic infections, most often while the South African HIV-infected children at a median of 16
number of CD4+ cell count is increasing and/or the days (range, 7-115 days) post-ART initiation. Bacillus
plasma HIV RNA level is decreasing [11,12,15,16]. This Calmette-Guérin reaction (71%) and TB (35.3%) were
syndrome can be severe, and results in significant mor- the most common conditions in their children [18].
bidity and occasional mortality. The information about Similarly, Wang et al. reported an incidence of 20% of
incidence and spectrum of IRIS in HIV-infected children IRIS (19.8 events per 100 person years) in HIV-infected
was limited. Puthanakit et al. reported an incidence of children in Peru with 6.6 weeks (range, 2-32) median
Figure3PhotomicrographofPenicilliummarneffei(courtesyofKornkanokSukapan)intheskinlesionsectionstainedwithGrocott
MethenamineSilver.Numerousintracellularandextracellular,roundtooval,elongated,thin-walledyeast-likeorganisms.Thecharacteristic
transverseseptum(arrows)withintheyeastcellisseen.Magnification,×1000.
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time to IRIS. The most common IRIS events were VZV similar to those observed in tuberculosis and systemic
infection (33.3%), HSV labialis (33.3%), and TB infection mycoses other than penicilliosis [28].
(22.2%) [19]. Diagnosis of infection by P. marneffei is usually made
Our patient developed symptoms 8 weeks after the by identifying the fungus in clinical specimens by micro-
initiation of ART, which is a common period for IRIS scopy and culture. In addition, P. marneffei can be seen
development. They included fever, multiple painful oral in histopathological sections stained with H&E, GMS, or
ulcers, disseminated umbilicated papular skin lesions PAS stain, which typically appears as unicellular round
over the face, body and extremities, and multiple swol- to oval yeast cells with transverse septum in macrophage
len, warm, and tender joints which are typical clinical or histiocyte [29]. This finding is unique to infection
presentations of disseminated P. marneffei infection. Tis- with P. marneffei. All 4 previously reported cases had
sue sections of the skin biopsy stained with H&E, PAS, evidences of the fungus in the clinical specimens,
and GMS revealed numerous yeast cells of P. marneffei, including blood, skin biopsies, and lymph node biopsies
but culture did not yield the organism These signs and and culture [21-24]. However, in our reported case, we
symptoms, especially prominent inflammatory articular found the evidences of organism in histopathological
manifestations, and an excessive inflammation reaction sections with special stains but could not identify fungus
in histopathology of the skin biopsyspecimen demon- by culture of the clinical specimens. This might be due
strated vigorous immune recovery which acted on unvi- to the fact that the organism was already killed by the
able P. marneffei antigens. Improvement of her immune immune system of the patient.
response was also evidenced by her rising CD4+ cell Treatment of disseminated P. marneffei infection is well
count and undetectable plasma HIV RNA level. The described [30]. Intravenous amphotericin B for 2 weeks
improved immune response had unmasked a previously followed by oral itraconazole for 10 weeks is recom-
quiescent P. marneffei infection causing the patient’s mended. Although itraconazole maintenance treatment
symptoms. was shown to prevent relapse of penicilliosis when the
P. marneffei is an important causative organism of patients had CD4 cell count of 100 cells/μl or greater for
opportunistic infection in immunocompromised people, at least 6 months after HAART [31], our patient who
particularly HIV-infected persons who live in or travel unintentionally discontinued maintenance treatment after
to Southeast Asia [4-7,20]. By reviewing the English 4-month therapy without knowing the CD4 cell count
medical literature, P. marneffei had been reported as a did not have relapse. Details of treatments and outcomes
causative organism of IRIS in only 4 HIV-infected were available in 3 of 4 previously reported cases (Table
patients. The first case was reported in 2007 from India 2). Two cases (case 1, 4) were treated with intravenous
[21]. Since then, there have been 2 additional cases amphotericin B for 2 weeks, followed by oral itraconazole
reported from the Indian subcontinent [22,23], and 1 for 10 weeks. The other case (case 3) received single dose
case from United Kingdom who had traveled to Thai- of intravenous amphotericin B because the patient
land [24]. Case histories and the characteristics of these refused to stay in the hospital. Therefore, he was treated
4 cases are summarized in Table 2. All patients lived in by only itraconazole orally for 8 weeks. All 3 cases were
or traveled to an endemic area of P. marneffei. Similar continued on maintenance treatment with oral itracona-
with our patient, all except one case (case 1) had evi- zole along with the ART. Their symptoms improved
dences of immune recovery during IRIS presentation markedly after 2-10 months of the therapy.
which occurred within 2-4 weeks after ART initiation. In summary, IRIS is not a rare condition, especially in
Both kinds of IRIS presentations were reported, 3 as the ART era. IRIS caused by P. marneffei infection will
unmasking, and 1 as paradoxical types. All except 1 be increasingly recognized in the endemic area of the
patient (case 1) had generalized skin and/or mucocuta- fungus. It requires appropriate recognition and proper
neous lesions which are the common clinical character- treatment. The clinicians’ awareness is crucial to ensure
istics of P. marneffei infection. The common presenting a good prognosis.
symptoms were generalized skin and/or mucocutaneous
lesions, pyrexia, lymphadenopathy, hepatomegaly and Consent
splenomegaly. Our patient also had osteoarticular invol- Written informed consent was obtained from the parents
vement by clinical and/or radiological findings, similar of the patient for publication of this case report and any
to case 2 in Table 2. The osteomyelitis was seen in mul- accompanying images. A copy of the written consent is
tiple including flat bones, long bones of the extremities available for review by the Editor-in-Chief of this journal.
and the small bones of hands and feet. The arthritis
could involve both large peripheral joints and small Funding
joints of the fingers [20,25-27]. These findings were None.
Table 2Immunereconstitution inflammatory syndrome with disseminated Penicillium marneffei infection in HIV-infected patients:Literature review
hS
Case Country Age Sex StatusbeforeARTcommencement Type Typeof Time StatusduringIRISpresentation Method Treatments Outcomes ttpud
ryeepaorrted (yr) oAfRT IRIS tIRoIS fdoiargnosis ://wwjaritru
onse wk
Clinicalsymptoms CD4 Viral Clinicalsymptoms CD4 Viral .biom.etal
cell load cell load e B
d M
count (copies/ count (copies/ ce C
1 India24, 35 M fever,lossofweight 4(mcemll3s)/ mNAL) d4T, unmasking 4 afebrile,pallor,mild (mNcAemll3s)/ NmAL) axillaryLN AmphoB0.6MKD At10mo;20 ntral.com Infectiou
2007 andappetite, 3TC, weeks icterus,cervicaland biopsy- for14days, kgweight /1 sD
hheeprpaetossgpelennitoamlisegaly, NVP alhyxemipllpaarthyoasdpelennoopmatehgy,aly pLpNoossciittuiivvlteeu,re- fimtorlagloc/odwnefaodzrob1ley04w0k0s, gdofaeicLnrN,e,aslievesri,ze 471-233 iseases
42
blood thenMTwith200 spleen,CD4 /101
c-puoltsuitrieve, mg/d =mm2234cells/ 2/282,12
:2
2 India25, 12 M fever,cough,weight 11 NA d4T, paradoxical 4 fever,severearthritis, 172 NA blood NA NA 8
2009 loss,diarrhea, 3TC, weeks exacerbrationofskin (wk4) culture-
generalizedpapular EFV lesions,generalised positive
umbilicatedlesion, lymphadenopathy
oralandesophageal
candidiasis
3 India26, 28 M fever,cough,lossof 47 NA d4T, unmasking 2 multipleerythrematous, 160 NA skin AmphoB0.6MKD At2mo;14
2010 weight,diarrhea,oral 3TC, weeks scaly,papulesand (wk2) biopsy- only1dose,then kgweight
candidiasis NVP noduleswithcentral positive, itraconazole400 gain,skin
necrosisonface skin mg/dfor2mo, lesions
extremities,scortum culture- thenMTwith200 disappear
positive, mg/d
blood
culture-
negative
4 UK 39 M fever,lossofweight 72 38000000 TDF, unmasking 4 multiplefaciallesions, 273 3log pus AmphoB0.6MKD At2mo;skin
(traveled andappetite,PJP, FTC, weeks disseminatednon- (wk8) drop culture- for14days, lesions
to molluscum EFV pruriticnodules,no (wk4) positive followedby regressAt28
Thailand) contangiosumon hepatosplenomegaly itraconazole600 mo;CD4=
27,2010 face mg/dfor10wks, 375cells/
thenMTwith200 mm3,VL<50
mg/d copies/mL
5 Thailand, 14 F fever,lossofweight 39 NA d4T, unmasking 8 fever,severe 51 <50 skin AmphoB0.7MKD At12mo;4
2011 andappetite,PJP, 3TC, weeks osteoarthritis, (wk14) (wk14) biopsy- for14daysthen kgweight
(Ours) herpeszosteron NVP disseminatednon- positive, Itraconazole5MK gain,CD4=
trunk pruriticpapulesand skin twicedailyfor10 269cells/
noduleswithcentral culture- weeks,thenMT mm3,VL<50
necrosis,oralulcer,no negative, with5MKDfor4 copies/mL
lymphadenopathy,no blood months
hepatosplenomegaly culture- Pa
g
negative e
5
Note:Mindicatesmale;d4T,stavudine;3TC,lamivudine;TDF,tenofovir;FTC,emtricitabine,EFV,efavirenz;NVP,nevirapine;LN,lymphnode;AmphoB,AmphotericinBdeoxycholate;MKD,mg/kg/day;MT, o
f
maintenance;VL,plasmaHIVRNAlevel;NA,notavailable 6
Sudjaritruketal.BMCInfectiousDiseases2012,12:28 Page6of6
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Ethical approval emergenceofauniquesyndromeduringhighlyactiveantiretroviral
therapy.Medicine2002,81:213-227.
This study was approved by Ethics Committee of
12. FrenchMA,PriceP,StoneSF:Immunerestorationdiseaseafter
Faculty of Medicine, Chiang Mai University, Chiang antiretroviraltherapy.AIDS2004,18:1615-1627.
Mai, Thailand. 13. FrenchMA:HIV/AIDS:immunereconstitutioninflammatorysyndrome:a
reappraisal.ClinInfectDis2009,48:101-107.
14. BoulwareDR,CallensS,PahwaS:PediatricHIVimmunereconstitution
inflammatorysyndrome.CurrOpinHIVAIDS2008,3:461-467.
Acknowledgements
15. MurdochDM,VenterWD,VanRA,FeldmanC:Immunereconstitution
TheauthorswouldliketothankPanneeVisrutaratna,ProfessorofRadiology,
inflammatorysyndrome(IRIS):reviewofcommoninfectious
DepartmentofRadiology,FacultyofMedicine,ChiangMaiUniversity,Chiang
manifestationsandtreatmentoptions.AIDSResTher2007,4:9.
Mai,Thailandforreviewingtheradiologicalstudiesofthispatient.Theauthors
16. HirschHH,KaufmannG,SendiP,BattegayM:Immunereconstitutionin
alsothankKornkanokSukapan,AssistantProfessorofPathology,Departmentof
HIV-infectedpatients.ClinInfectDis2004,38:1159-1166.
Pathology,FacultyofMedicine,ChiangMaiUniversity,ChiangMai,Thailandfor
17. PuthanakitT,OberdorferP,AkarathumN,WannaritP,SirisanthanaT,
performingtheorganismidentification.WewishtothanktheNational
SirisanthanaV:Immunereconstitutionsyndromeafterhighlyactive
ResearchUniversityProject(ChiangMaiUniversity)underThailand’sOfficeof
antiretroviraltherapyinHIV-infectedThaichildren.PediatrInfectDisJ
theHigherEducationCommissionforsupportingthepublication.
2006,25:53-58.
18. SmithK,KuhnL,CoovadiaA,MeyersT,HuCC,ReitzC,etal:Immune
Authordetails
reconstitutioninflammatorysyndromeamongHIV-infectedSouth
1DivisionofInfectiousDiseases,DepartmentofPediatrics,Facultyof
Africaninfantsinitiatingantiretroviraltherapy.AIDS2009,23:1097-1107.
Medicine,ChiangMaiUniversity,50200ChiangMai,Thailand.2Research
19. WangME,CastilloME,MontanoSM,ZuntJR:Immunereconstitution
InstituteforHealthSciences,ChiangMaiUniversity,ChiangMai,Thailand.
inflammatorysyndromeinhumanimmunodeficiencyvirus-infected
childreninPeru.PediatrInfectDisJ2009,28:900-903.
Authors’contributions 20. SirisanthanaV,SirisanthanaT:DisseminatedPenicilliummarneffeiinfection
Allauthorscontributedtothiswork.TASandVSwereinvolvedinthedirect
inhumanimmunodeficiencyvirus-infectedchildren.PediatrInfectDisJ
clinicalcare(diagnosis,decisionmaking,andtreatment)ofthereported
1995,14:935-940.
patient.Bothprovidedthecorrespondingfigures.Allauthorsinvolvedinthe
21. GuptaS,MathurP,MaskeyD,WigN,SinghS:Immunerestoration
preparationofthemanuscript.Allauthorsreadandapprovedthefinal syndromewithdisseminatedPenicilliummarneffeiandcytomegalovirus
versionofthemanuscript.
co-infectionsinanAIDSpatient.AIDSResTher2007,4:21.
22. SaikiaL,NathR,BiswanathP,HazarikaD,MahantaJ:Penicilliummarneffei
Competinginterests
infectioninHIVinfectedpatientsinNagaland&immunereconstitution
Theauthorsdeclarethattheyhavenocompetinginterests.
aftertreatment.IndianJMedRes2009,129:333-334.
23. SaikiaL,NathR,HazarikaD,MahantaJ:Atypicalcutaneouslesionsof
Received:10May2011 Accepted:31January2012 Penicilliummarneffeiinfectionasamanifestationoftheimmune
Published:31January2012
reconstitutioninflammatorysyndromeafterhighlyactiveantiretroviral
therapy.IndianJDermatolVenereolLeprol2010,76:45-48.
References 24. HoA,ShanklandGS,SeatonRA:Penicilliummarneffeiinfectionpresenting
1. ChiangCT,LeuHS,WuTL,ChanHL:Penicilliummarneffeifungemiainan asanimmunereconstitutioninflammatorysyndromeinanHIVpatient.
AIDSpatient:thefirstcasereportinTaiwan.ChanggengYiXueZaZhi IntJSTDAIDS2010,21:780-782.
1998,21:206-210. 25. JayanetraP,NitiyanantP,AjelloL,PadhyeAA,LolekhaS,AtichartakarnV,
2. DengZ,RibasJL,GibsonDW,ConnorDH:InfectionscausedbyPenicillium etal:PenicilliosismarneffeiinThailand:reportoffivehumancases.
marneffeiinChinaandSoutheastAsia:reviewofeighteenpublished AmJTropMedHyg1984,33:637-644.
casesandreportoffourmoreChinesecases.RevInfectDis1988, 26. LouthrenooW,ThamprasertK,SirisanthanaT:Osteoarticularpenicilliosis
10:640-652. marneffei.Areportofeightcasesandreviewoftheliterature.BrJ
3. HienTV,LocPP,HoaNT,DuongNM,QuangVM,McNeilMM,etal:First Rheumatol1994,33:1145-1150.
casesofdisseminatedPenicilliosismarneffeiinfectionamongpatients 27. ChanYF,WooKC:Penicilliummarneffeiosteomyelitis.JBoneJointSurgBr
withacquiredimmunodeficiencysyndromeinVietnam.ClinInfectDis 1990,72:500-503.
2001,32:e78-80. 28. DrouhetE:PenicilliosisduetoPenicilliummarneffei:anewemerging
4. RanjanaKH,PriyokumarK,SinghTJ,GuptaChC,SharmilaL,SinghPN,etal: systemicmycosisinAIDSpatientstravellingorlivinginSoutheastAsia.
DisseminatedPenicilliummarneffeiinfectionamongHIV-infected Review44casesreportedinHIVinfectedpatientsduringthelast5
patientsinManipurstate,India.JInfect2002,45:268-271. yearscomparedto44casesofnonAIDSpatientsreportedover20
5. SupparatpinyoK,KhamwanC,BaosoungV,NelsonKE,SirisanthanaT: years.JMycolMed1993,4:195-224.
DisseminatedPenicilliummarneffeiinfectioninSoutheastAsia.Lancet 29. VanittanakomN,CooperCRJr,FisherMC,SirisanthanaT:Penicillium
1994,344:110-113. marneffeiinfectionandrecentadvancesintheepidemiologyand
6. WongKH,LeeSS,ChanKC,ChoiT:RedefiningAIDS:caseexemplifiedby molecularbiologyaspects.ClinMicrobiolRev2006,19:95-110.
PenicilliummarneffeiinfectioninHIV-infectedpeopleinHongKong.IntJ 30. SirisanthanaT,SupparatpinyoK,PerriensJ,NelsonKE:AmphotericinBand
STDAIDS1998,9:555-556. itraconazolefortreatmentofdisseminatedPenicilliummarneffei
7. VanittanakomN,SirisanthanaT:Penicilliummarneffeiinfectioninpatients infectioninhumanimmunodeficiencyvirus-infectedpatients.ClinInfect
infectedwithhumanimmunodeficiencyvirus.CurrTopMedMycol1997, Dis1998,26:1107-1110.
8:35-42. 31. ChaiwarithR,CharoenyosN,SirisanthanaT,SupparatpinyoK:
8. SupparatpinyoK,PerriensJ,NelsonKE,SirisanthanaT:Acontrolledtrialof Discontinuationofsecondaryprophylaxisagainstpenicilliosismarneffei
itraconazoletopreventrelapseofPenicilliummarneffeiinfectionin inAIDSpatientsafterHAART.AIDS2007,21:365-367.
patientsinfectedwiththehumanimmunodeficiencyvirus.NEnglJMed
1998,339:1739-1743. Pre-publicationhistory
9. SinghN:PerfectJR.Immunereconstitutionsyndromeassociatedwith Thepre-publicationhistoryforthispapercanbeaccessedhere:
opportunisticmycoses.LancetInfectDis2007,7:395-401. http://www.biomedcentral.com/1471-2334/12/28/prepub
10. LawnSD,BekkerLG,MillerRF:Immunereconstitutiondiseaseassociated
withmycobacterialinfectionsinHIV-infectedindividualsreceiving doi:10.1186/1471-2334-12-28
antiretrovirals.LancetInfectDis2005,5:361-373. Citethisarticleas:Sudjaritruketal.:Immunereconstitution
11. ShelburneSA,HamillRJ,Rodriguez-BarradasMC,GreenbergSB,AtmarRL, inflammatorysyndromefromPenicilliummarneffeiinanHIV-infected
MusherDW,etal:Immunereconstitutioninflammatorysyndrome: child:acasereportandreviewofliterature.BMCInfectiousDiseases2012
12:28.