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

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.     

Penicillium marneffei infection in a lung transplant recipient

Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus‐1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41‐year‐old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas.     

Penicillium marneffei chylous ascites in acquired immune deficiency syndrome: A case report

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.     

Recurrent hemoptysis with Penicillium marneffei and Stenotrophomonas maltophilia in Job’s syndrome

Pulmonary infection caused by the opportunistic organisms Penicillium marneffei and Stenotrophomonas maltophilia in patients with Job’s syndrome is rare and not well documented. The case of a 30-year-old man with Job’s syndrome who developed recurrent pneumonia and lung abscesses caused by P marneffei and S maltophilia, complicated by massive hemoptysis, is described. Bronchial artery embolization was successful in controlling the hemoptysis; however, the infection proved fatal despite appropriate antimicrobial therapy. A brief review of the literature on Job’s syndrome and its associated infective pulmonary manifestations is also presented.     

Recovery from Talaromyces marneffei involving the kidney in a renal transplant recipient: A case report and literature review

Talaromyces marneffei is an emerging opportunistic infection among immunocompromised patients. We observe the first native case of disseminated T. marneffei involving the kidney in a renal transplant recipient in mainland China. We describe the comprehensive clinical course, and ultrasound imaging of renal transplant biopsy, pathologic images, and electron microscopy observation of the biopsy specimen, highlighting the relevance of biopsy findings and the blood culture. We also focus on the treatment and good outcome of the patient. Then we review the literature and show the additional 10 reported cases of T. marneffei in renal transplant recipients. In addition, we discuss the new methods of rapid diagnosis of T. marneffei. In brief, timely diagnosis and proper treatment of T. marneffei infection is important in renal transplant recipients.     

A Retrospective Analysis of 7 Human Immunodeficiency Virus-Negative Infants Infected by Penicillium marneffei

Infection with Penicillium marneffei has rarely been reported in human immunodeficiency virus (HIV)-negative infants. We aimed to determine the epidemiological, clinical, pathological, and immunological characteristics of 7 HIV-negative infants infected by P. marneffei, and to provide insights into its diagnosis and treatment.We retrospectively reviewed the cases of 7 HIV-negative infants infected by P. marneffei who presented to the First Affiliated Hospital of Guangxi Medical University between January 1, 2003 and December 1, 2014. The infants’ median age was 23.43 months (SD = 8.34), and all lived in Guangxi Province in China, where P. marneffei is endemic. The median time from disease onset to diagnosis was 2.29 months (SD = 2.12). Of the cases studied, 5 (71.43%) had medical histories that included frequent pneumonia or bronchopneumonia, thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia, followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four patients had slightly elevated white blood cell counts. The lymphocyte and CD4⁺ T-cell counts were normal. The CD8⁺ T-cell counts, serum immunoglobulin (Ig) G titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes were affected. One case who received intravenous amphotericin B and 3 cases who received intravenous voriconazole improved, and these patients were cured after continual treatment with oral voriconazole for 6 or 12 months. The remaining patients died before they received antifungal treatment.P. marneffei causes severe disease and disseminated infections, and it has high mortality rates in HIV-negative infants in endemic areas. P. marneffei susceptibility may be associated with immunodeficiencies or immune disorders. In endemic areas, clinicians should aware of disseminated P. marneffei infections when infants present with serious or recurrent infections, even if they are HIV negative. P. marneffei is highly susceptible to amphotericin B and voriconazole. Timely diagnosis and treatment can improve patients’ prognoses. Intravenous voriconazole could be recommended as the initial antifungal agent for HIV-negative infants infected by P. marneffei, because of its low nephrotoxicity, high sensitivity, and high efficacy levels.     

Talaromycosis in a renal transplant recipient returning from South China

Talaromycosis is a fungal infection endemic in Southeast Asia. We report a case of a renal transplant recipient who developed infection after a trip to South China. She presented with constitutional symptoms and was found to have an FDG‐avid lung mass. Histopathology demonstrated small yeast cells and culture grew Talaromyces marneffei. The patient was treated with 2 weeks of liposomal amphotericin B followed by itraconazole. The dose of tacrolimus was significantly reduced because of the interaction with itraconazole. Mycophenolate mofetil was discontinued. After 12 months of treatment, the mass had completely resolved. Talaromycosis has mainly been reported in patients with AIDS and is uncommon among solid organ transplant recipients. The immune response against T. marneffei infection is mediated predominantly by T cells and macrophages. The diagnosis may not be suspected outside of endemic areas. We propose a therapeutic approach in transplant patients by extrapolating the evidence from the HIV literature and following practices applied to other endemic mycoses.     

Aetiology of cavitary lung lesions in patients with HIV infection*

Background

Although many studies have been carried out on pulmonary diseases in HIV‐infected patients, studies specifically investigating the aetiologies of cavitary lung lesions are rare.

Methods

HIV‐infected patients enrolled in a cohort study who presented with cavitary lung lesions by radiography were identified between June 1994 and March 2008. Medical records and radiological and microbiological data for these patients were retrospectively reviewed using a standardized case collection form.

Results

During the 14‐year study period, 73 episodes of cavitary lung lesions were diagnosed in 66 of 1790 (3.7%) HIV‐infected patients. At the diagnosis of cavitary lung lesions, the median CD4 count was 25 cells/μL (range 1–575 cells/μL). Eighty‐one pathogens were considered causative, with fungi being the most common aetiology (42.0%), followed by bacteria (29.6%) and mycobacteria (25.9%). Of the fungal pneumonias, 19 (55.9%) were caused by Penicillium marneffei, 11 (32.4%) by Cryptococcus neoformans, two (5.9%) by Pneumocystis jirovecii, and two (5.9%) by Aspergillus species. During the study period, 11 of 205 patients (5.4%) who were diagnosed as having tuberculosis presented with cavitary lung lesions, compared with 19 of 36 patients (52.8%) with penicilliosis and 11 of 64 patients (17.2%) with cryptococcosis (P<0.0001). The median CD4 count of patients with cavitary lung lesions resulting from tuberculosis (115 cells/μL) was significantly higher than that of patients with cavitary lung lesions resulting from penicilliosis (4 cells/μL) and cryptococcosis (29.5 cells/μL).

Conclusions

Our findings suggest that invasive infections attributable to endemic fungi were the leading cause of cavitary lung lesions among patients in the late stage of HIV infection, and were more common than infections attributable to bacteria and mycobacteria.     

Identification of fungal DNA in BALF from patients with home-related hypersensitivity pneumonitis

Background

In Japan, a major type of home-related hypersensitivity pneumonitis (HP) is summer-type HP, which is caused by Trichosporon asahii (T. asahii) or Trichosporon mucoides. Some patients with home-related HP test negative for antibodies against Trichosporon; yet, a causative mold antigen cannot be identified.

Methods

We analyzed 19 patients with home-related HP, 8 healthy volunteers, and 35 patients with other diseases. We extracted DNA from cell pellets of bronchoalveolar lavage fluid (BALF), amplified the DNA by PCR using Trichosporon-specific primers or other fungus-specific primers, and cloned as well as sequenced the PCR amplicon. Other primers used were specific for Acremonium chrysogenum, Aspergillus fumigatus, Aspergillus niger, Fusarium napiforme, Humicola fuscoatra, Penicillium corylophilum, and Pezizia domiciliana.

Results

We detected Trichosporon DNA (n = 17) and F. napiforme DNA (n = 2) by PCR in 19 patients with home-related HP; however, these species were not identified in healthy volunteers. After sequencing of the PCR amplicon for Trichosporon species, we identified T. asahii (n = 11), Trichosporon japonicum (n = 1), and Cryptococcus uzbekistanesis (n = 4).

Conclusion

We could detect fungal DNA in BALF cell pellets from patients with home-related HP. These data suggest that this method might be useful to detect antigens responsible for home-related HP.     

Clinical impact of nosocomial infection with pandemic influenza A (H1N1) 2009 in a respiratory ward in Guangzhou

BackgroundNosocomial outbreaks of pandemic influenza A (H1N1) 2009 virus [A(H1N1)pdm09] easily develop due to its high transmissibility. This study aimed to investigate the clinical impacts of a nosocomial outbreak of A(H1N1)pdm09 between 21 January and 17 February 2016.MethodsPatients who developed influenza-like illness (ILI) more than 48 hours after hospitalization in the index ward were enrolled as suspected patients, defined as group A and quarantined. Patients in other wards were defined as group B. A phylogenetic tree was constructed to determine the origins of the hemagglutinin and neuraminidase genes.ResultsAfter the implementation of an infection control measure bundle, the outbreak was limited to eight patients with ILIs in group A. Nasal swabs from seven patients were positive for A(H1N1)pdm09. All the patients recovered after treatment. Prolonged viral shedding was observed in a patient with bronchiectasis and Penicillium marneffei infection. Compared to the expected duration of hospitalization in patients without fever, those with fever had a median 7-day delay in discharge and a mean excess cost of 3,358 RMB. The four influenza strains identified were genetically identical to the A/California/115/2015 strain. Six of the 54 patients in group B who underwent bronchoscopy developed transient fever. These patients were hospitalized in various wards of the hospital and recovered after a short-term course of empirical antibiotics.ConclusionsAfter the implementation of infection control measures, the nosocomial A(H1N1)pdm09 outbreak was rapidly contained; infected patients had a delay in discharge and excess costs, but no deaths occurred.     

Clinical Relevance of cagE Gene from Helicobacter pylori Strains in Japan

It has been reported that H. pylori-containing cagE was associated with duodenal ulcer. The aims of the present study were to clarify the association between the cagE gene and clinical outcome and to analyze the relationship between the cagE gene and two other virulence factors—cagA and vacA—in two areas in Japan (Fukui and Okinawa) where the prevalence of duodenal ulcer and gastric cancer risk are quite different. Eighty of 81 isolates possessed the cagE gene, and all isolates possessed the cagA gene. The vacA genotype s1c/m1 was a major genotype in both areas in Japan. There was no significant association between cagE, cagA status, or vacA genotype and clinical outcome. Phylogenetic analysis of the cagE gene indicated that most Japanese isolates formed a different cluster from strains isolated in the West with an association with the vacA genotype. In conclusion, the strains with cagE, cagA, and the s1c/m1 genotype of vacA are predominant in Japan regardless of clinical outcome and construct a different phylogenetic cluster from those in the West.     

Lutzomyia (Pintomyia) fischeri (Diptera: Psychodidae: Phlebotominae), a probable vector of American cutaneous leishmaniasis: detection of natural infection by Leishmania (Viannia) DNA in specimens from the municipality of Porto Alegre (RS), Brazil, using multiplex PCR assay

In order to determine natural Leishmania (Viannia) infection in Lutzomyia (Pintomyia) fischeri, a multiplex PCR methodology coupled to non-isotopic hybridization was adopted for the analysis of sand fly samples collected by CDC light traps in an endemic area of American Cutaneous Leishmaniasis (ACL) in the periurban region of the municipality of Porto Alegre, Rio Grande do Sul State, Brazil. We analyzed by PCR methodology 560 specimens of Lutzomyia (Pintomyia) fischeri (520 females and 40 males). The wild sand flies were grouped into 56 pools (52 females and 4 males) of 10 each, and positive results were detected in 2 of the 52 female pools, representing a minimum infection rate of 0.38% based on the presence of at least 1 infected insect in the pool. This result associated with some local evidence such as anthopophily, spatial distribution in accordance with the transmission area and human case incidence, suggests that L. (P.)fischeri may be considered as a secondary vector of ACL in the studied locality.     

Analysis of neuroendocrine differentiation and the p53/BAX pathway in UICC stage III colorectal carcinoma identifies patients with good prognosis

Background and aims Neuroendocrine differentiation is an independent prognostic factor in colorectal cancer. Moreover, an altered p53/BAX pathway is associated with a poor clinical outcome in Union Internationale Contre le Cancer (UICC) stage III disease. Because these markers are involved in different genetic events disrupted in colorectal cancer, we investigated the prognostic power of a multimarker analysis.Patients and methods Specimens were analyzed from 59 patients with UICC stage III disease who underwent surgery for colorectal adenocarcinoma at our institution and were followed up for 5 years or until death. Tumors were studied for both p53 mutation and BAX protein expression as well as for the expression of neuroendocrine markers. Statistical analysis of each marker alone or in combination was performed.Results p53 status/BAX expression and neuroendocrine differentiation are not correlated in stage III colorectal cancers. However, the combination of both independent events identified a subgroup of patients with an excellent prognosis: Patients whose tumors were neuroendocrine marker-negative and who exhibited an intact p53/BAX pathway lived longer (mean survival, 93 months; range, 82–104 months) than patients whose tumors were either neuroendocrine marker-positive or whose tumors had a completely disrupted apoptotic pathway (41 months; range, 26–57 months; p<0.00001). In multivariate regression analysis, neuroendocrine marker-positive, p53 mutated, low-BAX-expressing tumors revealed an almost fivefold higher risk for earlier death (p<0.0001).Conclusion Disruption of the p53/BAX pathway is not pathognomonic for colorectal cancers with neuroendocrine differentiation. Both represent independent prognostic markers in UICC stage III disease. Therefore, the combined analysis of p53 status, BAX expression and neuroendocrine differentiation allows one to identify subgroups of patients with either very good or very poor prognosis.P. Grabowski and I. Sturm contributed equally to this work     

Analysis ofras mutations in human melanocytic lesions: activation of theras gene seems to be associated with the nodular type of human malignant melanoma

We have analyzed the Ha-ras, Ki-ras and N-ras gene for point mutations at codons 12, 13 and 61 via restriction fragment length polymorphism/polymerase chain reaction analysis and subsequent direct sequencing in non-cultured fresh-frozen tissues of 16 superficial spreading melanomas (SSM), 13 nodular malignant melanomas (NMM), 2 lentigo malignant melanomas (LMM), 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi from 38 patients. Mutations were found in 4 melanoma samples, all belonging to the nodular malignant type. Three of them were mutated in N-ras and one in the Ha-ras gene. Mutation in N-ras was also detected in the congenital nevus. All mutations were exclusively located at the first two base pairs of codon 61. No Ki-ras mutation was detected in any lesion. No mutation could be found in SSM and LMM in addition to dysplastic and normal nevi. The frequency ofras mutation in NMM was 31%, whereas in SSM it was 0%. Our study suggests (a) an association betweenras mutations (mainly N-ras) and the NMM as a subgroup of human melanoma; (b) that activation of Ki-ras is not involved in the pathogenesis of melanoma. The role of UV radiation in point mutations ofras genes in human melanoma is discussed. This investigation was supported by grant EV5V-CT92-0096     

Promoter methylation profile in gallbladder cancer

Background Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. Methods Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. Results All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. Conclusions The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.     

Fuhrmanolepis beskydensis n.sp. (Cestoda: Dilepididae) from woodcock Scolopax rusticola L.(Aves, Charadriformes) in Slovakia with comments on sytematics and nomenclature of the genus Fuhrmanolepis Spassky et Spasskaya, 1965

Summary   Fuhrma n olepis beskydensis n.sp. from woodcock, Scolopax rusticola L. in Slovakia is described based upon light microscope observation. The medium sized species possess a single crown of 21‘diorchid’ (wrench-shaped) hooks, 28–30 μm long. Irregularly alternating genital pores were combined with abnormal multiple shifting of pores within the lateral margins of strobila. Number of testes 18–25. Cirrus-sac and evaginated cirrus are 115–135 × 7–12 and 26 × 6–11 μm, respectively. The species is differentiated from closely related congeneric taxons and some other morphologically similar dilepidids. An attention is being paid to taxonomy and nomenclature of Fuhrma n olepis Spassky et Spaskaja, 1965 regarding an emendation of mentioned genus to Fuhrma nn olepis by Bona (1994a) and modification of its diagnosis.     

Correlation between anti-Proteus antibodies and isolation rates ofP. mirabilis in rheumatoid arthritis

In a survey of 89 RA patients, carried out under code,Proteus mirabilis was isolated from the urine of 63% (47/75) of female (P<0.001) and 50% (7/14) of male patients (P<0.001) compared to a frequency of isolation in healthy women of 32% (38/119) and 11% (13/115) in healthy men. There was no significant difference in isolation rates between 37 non-RA patients and healthy controls. Sera from 20 patients with RA and 20 healthy controls were tested againstP. mirabilis andEscherichia coli by an enzyme-linked immunosorbent assay. Antibodies againstP. mirabilis but not toE. coli were significantly higher in the RA patients than in healthy controls (P<0.001). Furthermore, a positive correlation was found between high anti-Proteus antibody levels in serum samples and the number of Proteus colony-forming units obtained from urine specimens of the 20 RA patients (r=+0.714,P<0.001). These results support the suggestion of an aetiopathogenic role forP. mirabilis in RA.     

DoesHelicobacter pylori-induced gastritis enhance food-stimulated insulin release?

The fact thatH. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whetherH. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients withH. pylori gastritis before and one month after the eradication therapy and also in 15H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients withH. pylori gastritis before the eradication were significantly (P<0.05) higher than those in theH. pylori-negative controls. After the eradication ofH. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P<0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P<0.001). These results suggest thatH. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.Presented in part as an abstract at the 8th Balkan Congress of Endocrinology, Bursa, Turkey, May 3–5, 1995.     

Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.