Disseminated Penicillium marneffei Infection in an HIV‐Positive Italian Patient and a Review of Cases Reported Outside Endemic Regions

Spinello Antinori MD, Erika Gianelli MD, Carmen Bonaccorso BSc, Anna Lisa Ridolfo MD, Francesco Croce MD, Salvatore Sollima MD, Carlo Parravicini MD
DOI: http://dx.doi.org/10.1111/j.1708-8305.2006.00039.x 181-188 First published online: 1 May 2006

Abstract

We describe a case of disseminated Penicillium marneffei in a human immunodeficiency virus (HIV)–positive Italian man who stayed for 4 years in Chiang Ray province, northern Thailand. A review of the literature shows that penicilliosis, although unusual, may represent an emerging opportunistic infection among HIV‐positive people traveling to endemic areas.

Penicillium marneffei, first discovered in 1956, is the only thermally dimorphic species of the genus Penicillium; 1 it is geographically restricted to Southeast Asia where it emerged as a significant opportunistic pathogen among human immunodeficiency virus (HIV)‐positive natives especially in Thailand where this infection is considered an acquired immunodeficiency (AIDS)‐defining illness. 2 The exact route of transmission of P marneffei in humans is unknown, but it is presumed that conidia may be inhaled from an environmental source and subsequently the fungus proliferates in macrophages and is disseminated to the reticuloendothelial system. The epidemiology of penicilliosis closely parallels that of AIDS epidemic in endemic countries. In the northern provinces of Thailand, penicilliosis represents the third commonest opportunistic infection reported in 6.8% of AIDS patients, whereas elsewhere in the country, it was observed in <1% of AIDS patients. 3 A high prevalence of the disease is also observed in Hong Kong where 7.7% of AIDS patients developed the penicilliosis during the course of the illness. 4

Here, we describe the second case of HIV‐associated penicilliosis marneffei from Italy together with a review of epidemiological, microbiological, and clinical characteristics of all cases described outside of endemic regions.

A Medline search from 1988 (when the first AIDS‐associated case outside an endemic region was described) to December 2004 yielded a total of 37 case reports of HIV‐associated penicilliosis. 5–37 However, two cases from the same institution were reported twice 16,18 and for the purpose of this review were considered once for a total of 35 cases. The terms used for the Medline search were P marneffei, AIDS, HIV, and imported. English, French, German, and Spanish languages articles were reviewed.

Case report

On August 14, 2004, a 36‐year‐old Italian man came to our attention by chance since his wife, a 32‐year‐old Thai woman, was referred to our department for a coma secondary to a space‐occupying central nervous system lesion. Both were HIV‐positive, and the infection was disclosed 2 months earlier in Thailand where they lived in the northern province of Chiang Ray. During the interview, the physician in charge noted on the face of the husband several maculopapular lesions, some of which had a molluscum‐like appearance.

The man reported that these lesions appeared at the beginning of June, concomitantly with mild fever (37.5°C) and a 6 kg weight loss. Physical examination although revealing the presence of similar lesions on the arms, trunk and limbs were otherwise unremarkable (Figure 1A,B). The clinical picture and the geographic residence of the subject along with the known HIV infection were consistent with a presumptive diagnosis of penicilliosis. The patient underwent hematochemical blood examinations, chest X‐ray, skin biopsy, blood cultures, and bone marrow aspirate and started an antifungal treatment with oral itraconazole (600 mg/d). Laboratory investigations showed a mild anemia with a hemoglobin of 11.1 g/dL, white blood cells 3.9 × 109/L, platelets 239 × 109/L, CD4 cell count of 6/μL, and HIV‐RNA viral load of 213,047 copies/mL. Chest X‐ray did not show any evidence of disease; cryptococcal serum antigen was negative. Skin biopsies showed necrotizing histiocytic granulomas in upper and reticular dermis. Tissue sections stained with hematoxylin–eosin, periodic acid–Schiff, and Gomori Methenamine Silver (GMS) Grocott–Gomori stains revealed numerous intra‐ and extracellular, round to oval, thin‐walled yeast‐like organisms, some of which had a central septation (Figure 1C); a few similar organisms were observed in the bone marrow aspirate.

Figure 1

Several papular necrotic skin lesions on the right arm of the patient (A); papular and dome‐shaped lesions with slight central umbilication on the face (B); skin biopsy: clusters of Penicillium marneffei yeast are dispersed among collagen fibers in the reticular dermis (GMS, ×250); (insets): higher magnification showing septate forms diagnostic for P marneffei infection (GMS, ×400) (C).

Within 5 days, cultures of blood, bone marrow, and skin on Sabouraud’s dextrose agar incubated at 37°C and at room temperature yielded yeast and mold forms identified as P marneffei. At this time, itraconazole was substituted with intravenous liposomal amphotericin B (3 mg/kg/d), and pneumocystis prophylaxis with cotrimoxazole (one double strength tablet, three times weekly) was started. After 2 weeks of intravenous antifungal therapy, blood cultures became negative and the patient was switched to oral itraconazole (400 mg/d) and started with antiretroviral therapy (ARV; stavudine, lamivudine, and efavirenz). He was discharged in good health, with almost complete disappearance of skin lesions.

The patient came back to Thailand where he continued the same ARV therapy; at the last available follow‐up, his CD4+ cell count was 292/μL, with an HIV‐RNA viral load of 93 copies/mL. At this time, antifungal maintenance therapy was discontinued by his local physician.

Discussion

Penicillium marneffei is the only dimorphic fungus member of the genus Penicillium and is able to infect both immunocompromised and healthy hosts. The fungus was first isolated in 1956 in Vietnam from the bamboo rat Rhizomys sinensis and was subsequently identified as a new species by Segretain who also described the first laboratory‐acquired human case. 1 At 25°C to 30°C, P marneffei grows as a mold and produces a pink or rose‐red pigment that diffuses throughout the medium. At 37°C, the fungus develops as a yeast‐like cell that divides by fission and appears as a cell with a centrally located transverse septum, a feature that allows to differentiate P marneffei from other dimorphic fungi, especially Histoplasma capsulatum.

In 1973, the first natural human infection was observed in a patient with Hodgkin’s disease who had traveled in Asia. 37 The first HIV‐related case was reported in 1988 in an American homosexual man; 5 since then, P marneffei has emerged as an opportunistic infection among HIV‐infected patients in Thailand, Myanmar, Vietnam, Cambodia, Malaysia, Hong Kong, Northeastern India, Taiwan, and southern China. However, the majority of patients have been reported from Thailand, with 1,173 HIV‐infected patients diagnosed at the Chiang May University Hospital from 1991 to 1997. 2 It is generally reported that in Thailand disseminated penicilliosis is now the third opportunistic infection after tuberculosis and cryptococcosis, but this figure is true only for the northern area of the country. 3 HIV infection is the single most important underlying condition for P marneffei infection, with less than 40 cases of penicilliosis marneffei reported prior to HIV pandemic. Since no patient was on successful highly active antiretroviral therapy (HAART) at the time of diagnosis, the influence of HAART on the clinical presentation of penicilliosis cannot be determined.

The epidemiological and clinical features of 35 cases associated with P marneffei–AIDS are shown in Table 1 together with those of our patient. Twenty‐eight (77.8%) occurred in male patients with a median age of 34 years (range 22–55 yr), and all but one were diagnosed during life (97%). Diagnosis was made by means of histology plus culture in 23 patients (63.9%), by culture alone in 11 patients (30.5%), and by histology alone in the remaining two patients (5.5%). The majority of patients presented with fever (88.9%), weight loss (66.7%), and skin lesions (52.8%); hepatomegaly was reported in 36.1% of cases and splenomegaly and lymphadenopathy in 33.3% each. Chest roentgenograms were available in 27 cases and showed alterations in 14 (51.8%). Penicilliosis marneffei occurred late during the course of HIV infection, with a median CD4 cell count at the time of diagnosis of 20 cells/μL (range 1–110/μL); 12 patients had a previous diagnosis of AIDS (34%) and three patients had a concomitant AIDS‐defining disease at the time of penicilliosis (one Kaposi’s sarcoma; one cryptococcosis, one Mycobacterium avium complex). Countries reporting the cases were with the following ranking: 1) France (nine cases); 2) UK (five cases); 3) United States, Netherlands, Switzerland, and Germany (three cases); 4) Australia, Belgium, and Italy (two cases); 5) Denmark, Japan, Spain, and Sweden (one case each). Except for one patient for whom no epidemiological information regarding travels was reported 5 and for two African patients who had never visited South‐east Asia 15,31 , all the remaining subjects were either natives or residents of Asia (10 from Thailand, 2 from Myanmar, 1 from China) or traveled to endemic areas (8 exclusively in Thailand; 9 in Thailand and other Asian countries; 5 in other Asian countries including Hong Kong, China, India).

View this table:
Table 1

Clinical and epidemiological characteristics of Penicillium marneffei infection reported outside endemic areas

Patient No. (Reference No)/country/YearAge/Sex/RFEpidemiologyCD4+/μL/AIDS*Clinical features/radiologyLaboratory alterationsDiagnosisTreatment/outcome
1 (5)/United States/198833/M/MSMNR10/NoFever, anorexia, papular skin lesions, weight loss/chest X‐ray: NRNRSkin, BM (H, Cx); blood, sputum, stool (Cx)AMFB/relapse 6 mo after diagnosis (2 mo after antifungal discontinuation)
2 (6)/France/198830/M/MSMTravel to Indonesia, Southeast AsiaNR/NRFever; pleural and pericardial effusion/chest X‐ray: pulmonary infiltratesNRBlood, pleural effusion, BAL (Cx)NR
3 (7)/UK/198846/M/MSMTravel to Hong Kong, western China, Nepal, India (visit bat caves)NR/NoFever, weight loss; cough, diarrhea, night sweats, skin lesions (mc‐like), oral ulcer, dysphonia; melaena/chest X‐ray: negativeAnemia, thrombocytopeniaSkin (H), blood (Cx), BM (H, Cx)AMFB (1.5 g) + ketoconazole 400 mg/d (I); ketoconazole 200 mg/d (M)/alive 6 mo after diagnosis
4 (8)/France/198940/M/MSMTravel to Thailand, Myanmar60/NoFever; cough; nausea; weight loss; night sweats/chest X‐ray: negativeNRBAL (H, Cx)Ketoconazole 400 mg/d/(I)/alive 7 mo after diagnosis
5 (9)/Netherlands/199047/M/MSMTravel to ThailandNR/NoFever, hepatosplenomegaly/chest X‐ray: diffuse infiltrate; brain CT: enhancing massNRLi (Cx), positive serologyAMFB + flucytosine (I)/died few days later autopsy: Staphylococcus aureus meningitis; PCP; P marneffei (L, Li)
6 (10)/Australia/199233/M/MSMTravel to Hong Kong, Southern China10/No concomitant MACWeight loss, diarrhea, generalized skin lesions (mc‐like), oral lesions/chest X‐ray: NRPancytopeniaSkin (H, Cx), BM (Cx)Itraconazole 200 mg/d (I)/died 3 mo after diagnosis
7 (11)/Italy/199233/M/IVDATravel to Thailand46/Yes (PCP)Fever; productive cough; maculopapular, pustular skin lesions; hepatomegaly; lymphadenopathy/chest X‐ray: lobar infiltratePancytopeniaBlood, sputum (Cx); skin (H, Cx)AMFB 1400 mg (I); fluconazole 150 mg/d + itraconazole (M)/died 7 mo after diagnosis of pneumonia
8 (12)/France/199332/M/IVDATravel to India, Thailand, Malaysia, Indonesia46/NoFever, weight loss, abdominal pain, skin lesions (papules), hepatosplenomegaly, pericardial effusion/chest X‐ray: interstitial infiltrateAnemia, ↑ liver enzymesSkin, blood, urine, Li, stool (Cx)AMFB 635 mg (I); ketoconazole 400 mg/d (M)/alive 9 mo after diagnosis
9 (12)/France/199335/M/MSMTravel to Thailand, Myanmar, Laos, Malaysia71/Yes (Kaposi’s sarcoma; Salmonella sepsis)Fever, weight loss, headache, dry cough, nausea, vomiting, lymphadenopathy, hepatosplenomegaly/chest X‐ray: bilateral diffuse infiltratesAnemiaBlood, BM (Cx)AMFB 530 mg (I); ketoconazole 400 mg/d (M)/alive 7 mo after diagnosis
10 (13)/Switzerland/199335/M/MSMTravel to Thailand90/NoFever, malaise, weight loss, cough, skin lesions (mc‐like)/chest X‐ray: bilateral interstitial infiltratesNRBlood, BM, skin, tracheal biopsy, stool (Cx); BAL (H, Cx)AMFB (I)/NR
11 (14)/Netherlands/199433/M/MSMTravel to SumatraNR/NoFever, anorexia, cough, skin lesions, weight loss, splenomegaly, hypopharynx ulcer/chest X‐ray: NR↑ Liver enzymesLi, stomach ulcer (H); BAL (H, Cx)AMFB 730 mg + flucytosine 142 g (I); fluconazole 400 mg/d (12 wk) (M), fluconazole 200 mg/d/alive 24 mo later
12 (14)/Netherlands/199428/M/MSMTravel to ThailandNR/Yes (cerebral toxoplasmosis)Fever, dyspnea, lymphadenopathy, ulcerated painful oral lesion/chest X‐ray: NRNoOral lesions (H)AMFB 1052 mg (I)/Died 10 mo later (cryptosporidiosis)
13 (15)/France/199432/M/NRNative of Congo; laboratory acquired in France ?1/No (concomitant Kaposi’s sarcoma)Fever, headache, myalgia, asthenia, cough, skin lesions/chest X‐ray: negativeAnemia, leukopeniaSkin, blood, BM, oropharyngeal swab (Cx)AMFB 620 mg (I); ketoconazole 400 mg/d (M)/Died 1 y later of disseminated KS
14 (16, 18)/Switzerland/199443/M/IVDATravel to Thailand, Indonesia10/Yes (candida esophagitis; histoplasmosis)Weight loss, odynophagia; papular skin lesions, lymphadenopathy, hepatosplenomegaly/chest X‐ray: negativePancytopeniaBlood (Cx), BM, skin (H, Cx)AMFB 770 mg (I), itraconazole 400 mg/d (M)/alive 5 mo later
15 (16, 18)/Switzerland/199428/F/IVDATravel to Thailand, China, Taiwan4/Yes (candida esophagitis)Fever, weight loss, cough, lymphadenopathy/chest X‐ray: diffuse interstitial infiltratePancytopeniaBlood (Cx), Ly (H, Cx)AMFB 1 wk (I), itraconazole 400 mg/d (M)/relapse after 3 mo
16 (17)/Australia/199539/M/BisexualNative of Myanmar; travel to Thailand0/NoFever, rigor, malaise, productive cough, weight loss, skin lesions (mc‐like), hepatosplenomegaly/chest X‐ray: negativePancytopeniaSkin (H, Cx), blood (Cx)AMFB 500 mg (I), itraconazole 400 mg/d (M)/alive 5 mo after diagnosis
17 (19)/Germany/199633/M/MSMTravel to Thailand20/NoFever, headache, night sweats, weight loss, dysphagia, hepatosplenomegaly, skin lesions (mc‐like)/chest X‐ray: negative↑Liver enzymesBM (H, Cx), throat (Cx)Itraconazole 400 mg/d (I), itraconazole 200 mg/d (M)/NR
18 (20)/United States/1996NR/M/BisexualNative of ThailandNR/noFever, weight loss, cough, skin lesions (papules), hepatosplenomegaly, lymphadenopathy/chest X‐ray: bilateral infiltrates + upper cavitationPancytopeniaSkin, BAL (H, Cx)AMFB 3 wk (I), itraconazole (M)/NR
19 (21)/Sweden/199738/M/IVDATravel to Thailand60/NoFever, chills, lymphadenopathy/chest X‐ray: mediastinal adenopathyAnemia, thrombocytopeniaLy (H, Cx), BAL (Cx)AMFB 45 mg/d (I), itraconazole 400 mg/d (M)/alive 9 mo later
20 (22)/France/199825/F/HeterosexualNative of Thailand110/YesFever, productive cough, weight loss/chest X‐ray: lobar infiltrate + nodular lesionsAnemiaBlood, BM (Cx); BAL (H, Cx)AMFB 3 d (I)/relapse 6 mo later; AMFB + itraconazole (I)
21 (23)/UK/199835/M/IVDATravel to Hong Kong, southern China20/Yes (PCP)Fever, cough, dyspnea, skin lesions (trunk, limbs), lymphadenopathy/chest X‐ray: opacity upper lobe + multiple nodulesAnemia, thrombocytopeniaSkin, pulmonary lesion, tracheal lesion (H, Cx)AMFB 2 d; itraconazole 400 mg/d (I)/died 18 mo after diagnosis (CMV)
22 (24)/France/199848/F/HeterosexualNative of Thailand; travel to Thailand8/NoFever, cough, weight loss/chest X‐ray: nodular lesionsAnemiaBlood, BAL (Cx)AMFB 1 mg/kg/d + itraconazole 400 mg/d (I)/died 2 mo after diagnosis of VZV encephalitis
23 (25)/United States/199855/M/NRTravel to Philippines, Indonesia, Peru, northern Thailand30/Yes Fever, sweats, weight loss, hepatosplenomegaly/chest X‐ray: negativePancytopenia, ↑ liver enzymesBM (H, Cx); blood (Cx)AMFB 30 mg/d (14 d) (I), itraconazole 400 mg/d (M)/alive 5 mo after diagnosis
24 (26)/Belgium/199834/F/HeterosexualNative of Thailand; travel to Thailand10/NoFever, headache, skin lesions (maculopapular), abdominal pain, lymphadenopathy/chest X‐ray: NR↑ Liver enzymesLi, skin (H); Blood, BM, skin, stool, urine, lip, throat (Cx)Itraconazole 400 mg/d for 2 mo (I); itraconazole 200 mg/d (M)/relapse 8 mo after diagnosis
25 (26)/Belgium/199834/F/HeterosexualNative of Thailand40/Yes (tubercular lymphadenitis)Fever, nausea, lymphadenopathy. Chest X‐ray: apical fibrosisPancytopenia; ↑ liver enzymesBM, Ly (Cx)Itraconazole 400 mg/d (I); itraconazole 200 mg/d (M)/alive 12 mo after diagnosis
26 (27)/Germany/199933/F/HeterosexualNative of Thailand; travel to Thailand18/NoFever, abdominal pain, night sweats, lymphadenopathy/chest X‐ray: NR; Abdominal CT: enlarged abdominal lymph nodesNRBlood (Cx); sputum, Ly (H, Cx, PCR)AMFB 0.6 mg/kg/d (2 wk) (I), itraconazole 400 mg/d/alive 10 mo later
27 (28)/France/199939/M/IVDALiving in Northern Thailand40/NoFever, fatigue, weight loss, lymphadenopathy/chest X‐ray: NR; Abdominal CT: enlarged abdominal lymph nodesNoBlood, BAL, Li (Cx), Ly (H, Cx)AMFB 1 mg/kg/d (3 wk) + itraconazole 400 mg/d (4 mo) (I); itraconazole 200 mg/d (M)/alive 7 mo later
28 (29)/France/200051/M/MSMTravel to Thailand, Indonesia, Cambodia, Laos10/Yes (Kaposi’s sarcoma)Fever, weight loss, hepatosplenomegaly/chest X‐ray: negativePancytopeniaBM (H, Cx)AMFB 14 d (I); itraconazole 400 mg/d (M)/alive 6 mo after diagnosis
29 (30)/UK/200031/M/IVDATravel to India, Nepal, ThailandNR/Yes (PCP)Papular skin lesions; visual blurring (endophthalmitis)/chest X‐ray: negativeLeukopeniaBlood (Cx); oral swab (H, Cx)AMFB + itraconazole (I), itraconazole 400 mg/d (M)/died 13 mo later
30 (31)/Germany/200038/M/HeterosexualNative of and living in Ghana27/Yes (Salmonella sepsis)Fever, weight loss, commissural ulcer, hepatosplenomegaly/chest X‐ray: negativePancytopeniaBlood, BM, urine (Cx)Itraconazole 400 mg/d (I)/NR
31 (32)/UK/200229/F/NRLiving in ThailandNR/NoHepatosplenomegaly/chest X‐ray: NRNRAutopsy diagnosisNot treated, died
32 (33)/Japan/200322/M/NRNative of Myanmar1/No (concomitant cryptococcosis)Fever, weight loss, dyspnea, pigmented skin lesions/chest X‐ray: NRPancytopeniaSkin (H, PCR)No treatment/Lost to follow‐up
33 (34)/Spain/200340/M/NRNative of China10/NFever, productive cough, weight loss, papular skin lesions/chest X‐ray: diffuse interstitial infiltrateAnemia, piastrinopenia, ↑ liver enzymesBlood, skin, BAL (Cx)LAMFB 3 wk (I); itraconazole (M)/died 6 wk after hospitalization
34 (35)/UK/200446/M/NRResident in Thailand (visited bat caves)60/NoFever, malaise, weight loss, night sweats, chills, productive cough, hepatomegaly, forehead rash/chest X‐ray: negativePancytopeniaLi (H, Cx)AMFB 1 mg/kg/d (I); itraconazole, fluconazole (M)/relapsed after 2 y, alive after 4 y
35 (36)/Denmark/200432/F/NR20/No Native of Thailand and living in Thailand20/NoFever, nausea, diarrhea, weight loss, dyspnea/chest X‐ray: negativeNoBlood (Cx)LAMFB 14 d (I); itraconazole 400 mg/d (M)/NR
36 (PR)/Italy/200436/M/HeterosexualItalian living in Thailand6/NoFever, weight loss, skin lesions (mc‐like)/chest X‐ray: negativeAnemia, leukopeniaSkin, BM (H, Cx); blood (Cx)Itraconazole 600 mg 7 d (I); LAMFB 2 wk (I)/itraconazole 400 mg/d (M); alive after 11 mo
  • M = male; F = female; RF = risk factor; MSM = men who have sex with men; IVDA = intravenous drug abuser; NR = not reported; MAC =Mycobacterium avium complex; PCP =Pneumocystis jirovecii pneumonia; KS = kaposi’s sarcoma; CMV = cytomegalovirus; VZV = varicella zoster virus; mc‐like = molluscum contagiosum‐like; H = histology; Cx = culture; PCR = polymerase chain reaction; BM = bone marrow; BAL = bronchoalveolar lavage; L = lung; Li = liver; Ly = lymph nodes; AMFB = amphotericin B deoxycholate; LAMFB = liposomal amphotericin B; I = induction; M = maintenance; PR = present report; AIDS = acquired immunodeficiency.

  • * Previous diagnosis.

  • Based only on laboratory findings (ie, CD4 < 200/mL).

Thirty‐three patients received antifungal therapy: amphotericin B dehoxycholate alone (17, 51.5%) or in combination with azoles (7, 21.2%) was the drug most frequently employed. Six patients (18.2%) were treated with itraconazole, two with liposomal amphotericin B and one with ketoconazole. Overall, 10 patients died, with a median of 8.5 months after the diagnosis of penicilliosis. Twenty‐five patients received maintenance therapy with itraconazole (18, 72%), ketoconazole (5, 20%), and fluconazole (2, 8%); five patients relapsed, one of which after discontinuation of antifungal secondary prophylaxis.

Interestingly, the first reported African patient was assumed to have been infected while attending a 4‐month course of tropical microbiology at the Institute Pasteur in Paris although attempts to culture P marneffei from air samples taken either from the patients’ home or from the building of Institute Pasteur were unsuccessful. 15 The second African patient was a 38‐year‐old Ghanese man who had been working as a fruit picker in Africa and was diagnosed shortly after his arrival in Germany; also in this case, no exposition in endemic areas was reported. 31 Both cases raise the suspicion and the possibility that the fungus is not geographically restricted to Southeast Asia and Indonesia.

The clinical course of our patient was relatively indolent despite the disseminated nature of the disease, so he would not search for clinical care unless the wife’s illness.

In our experience, the presence of the skin lesions together with the geographic provenience of the patients was the clue to the diagnosis; however, in this review of 36 HIV‐positive patients observed outside endemic areas, cutaneous lesions were found only in 52% of cases, a percentage lower than that reported in Thailand (70%–75%). 2 Penicillium marneffei skin lesions have to be differentiated from those due to histoplasmosis as well as from other opportunistic infections, ie, cryptococcosis and tuberculosis, all of which (except histoplasmosis) are frequent in countries where P marneffei is endemic. Moreover, from a pathologic point of view, it is worth noting that the fungus may be overlooked or misdiagnosed (especially as Leishmania or Histoplasma) in tissue preparation stained with hemotoxylin and eosin, as documented in four reports. 7,18,29,35

Penicillium marneffei is susceptible to amphotericin B and itraconazole in vitro, whereas the susceptibility to fluconazole and 5‐fluorocytosine is less uniform. In one nonrandomized study, 2 weeks of intravenous amphotericin B (0.6 mg/kg daily) followed by 10 weeks of oral itraconazole resulted in clinical and microbiological cure in 97% of the patients. 38 A double‐blind placebo‐controlled randomized trial clearly demonstrated the efficacy of secondary itraconazole prophylaxis in preventing relapse of the disease. 39 The feasibility of discontinuation of antifungal prophylaxis among HIV‐infected patients with penicilliosis marneffei who respond to HAART was so far demonstrated only in one small study involving nine patients. 40

In conclusion, since travel to Southeast Asia is increasing, P marneffei needs to be considered in all HIV‐positive patients presenting with fever (with or without skin lesions), and a thorough travel history assists in making a prompt diagnosis.

Acknowledgments

We are indebted to Mrs. Bianca Ghisi and Mrs. Valeria Vimercati for their help and technical assistance.

Declaration of interests

The authors state that they have no conflicts of interest.

References

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