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Background: Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes., Methods: We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed., Results: A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately., Conclusions: Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dai, Lou, Yu, Chen and Lu.)

Talaromyces marneffei (TSM) is a temperature-dependent dimorphic fungus endemic to Southeast Asia and southern China. As the number of people at risk of TSM infection continues to increase, the clinical manifestations are becoming increasingly complex, posing challenges for clinical management. In this study, we analyzed the medical records of 99 patients (71 human immunodeficiency virus [HIV]-positive and 28 HIV-negative) diagnosed with TSM infection from January 1, 2017, to December 31, 2022, in southern China and compared the clinical manifestations in HIV-positive and HIV-negative patients. Most patients (83/99, 84%) were male. The incidence of skin and soft tissue involvement (48% vs. 21%, P = .016); disseminated infection with blood circulation, hematopoietic, lymphatic, alimentary, or central nervous system involvement (69% vs. 36%, P = .002); and gastrointestinal bleeding (33% vs. 9%, P = .023) was higher in the HIV-positive group than the HIV-negative group. The HIV-positive group also had significantly higher alanine aminotransferase (ALT) levels (31 [26-42] vs. 14 [11-16] U/l, P < .001) and ALT/aspartate transaminase ratio (1.9 [1.5-2.2] vs. 1.3 [1.1-1.6], P = .006) than the HIV-negative group. The time to diagnosis (5.5 ± 1.1 vs. 5.1 ± 1.4 days, P = .103), antifungal regimen (P = .278), case fatality rate (20% vs. 21%, P = .849), and relapse/reinfection rate (11% vs. 19%, P = .576) did not differ significantly between the HIV-positive and HIV-negative groups. Poor antiretroviral therapy adherence (OR = 26.19, 95%CI 3.26-210.70, P = .002), advanced age (OR = 1.13, 95%CI 1.03-1.23, P = .010), and Epstein-Barr virus co-infection (OR = 37.13, 95%CI 3.03-455.64, P = .005) were independent risk factors for all-cause mortality from TSM infection in HIV-positive patients. Overall, the predominant infection sites, clinical manifestations, and complications of TSM infection differed by HIV status. However, with prompt diagnosis and appropriate treatment, HIV-positive patients with TSM infection can have similar outcomes to HIV-negative patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Pneumocystis jirovecii is an opportunistic fungus that can cause severe and potentially fatal Pneumocystis pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of P. jirovecii at eight different loci, including six nuclear genes (ITS, 26S rRNA, sod , dhps , dhfr and β-Tub) and two mitochondrial genes (mtLSU-rRNA and cyb ) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of P. jirovecii at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of P. jirovecii at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes ( dhfr, dhps and cyb ) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of P. jirovecii in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of P. jirovecii in China., (© 2022 Ting Xue et al., published by Sciendo.)

BACKGROUND Cryptococcal meningitis (CM) is one of the most common opportunistic neuroinfections in patients with HIV. Most studies have focused on non-HIV CM and there are only a few studies on HIV CM in China. The purpose of the present study was to evaluate the characteristics and risk factors for CM recurrence in patients infected with HIV in the Chongqing Public Health Treatment Center in China. MATERIAL AND METHODS From January 2014 to December 2017, all patients with CM aged 18 years or older were enrolled and a case-control study was performed to determine the risk factors associated with recurrence of CM. Antimicrobial susceptibility was determined with a fungal drug sensitivity kit and the sequence types (STs) were analyzed with multilocus sequence typing. RESULTS The incidence of CM in the 5185 HIV-infected patients was 3.5% (179). Follow-up data were available for 82 of the patients for whom complete medical records were available and they were included in the present study. There were 7 STs among 82 Cryptococcus neoformans isolates; ST5 and ST31 were the most prevalent genotypes. Testing showed that C. neoformans had high sensitivity to 5 antifungal drugs and no differences in resistance were observed, even when different STs were tested. Risk factors for recurrence were analyzed in 69 patients, excluding those who died. The results of multivariate analysis showed that only hospital stay was associated with recurrence of CM. CONCLUSIONS Our results indicated that combining education about medication with clinical treatment could help prevent recurrence of CM.

Background: The clinical and laboratory characteristics of AIDS-associated Talaromyces marneffei infection, a rare but a fatal mycosis disease of the central nervous system, remain unclear., Case Presentation: Herein, we conducted a retrospective study of ten AIDS patients with cerebrospinal fluid culture-confirmed central nervous system infection caused by Talaromyces marneffei. All 10 patients were promptly treated with antifungal treatment for a prolonged duration and early antiviral therapy (ART). Among them, seven patients were farmers. Nine patients were discharged after full recovery, while one patient died during hospitalization, resulting in a mortality rate of 10%. All patients initially presented symptoms and signs of an increase in intracranial pressure, mainly manifesting as headache, dizziness, vomiting, fever, decreased muscle strength, diplopia or even altered consciousness with seizures in severe patients. Nine patients (90%) showed lateral ventricle dilatation or intracranial infectious lesions on brain CT. Cerebrospinal fluid findings included elevated intracranial pressure, increased leukocyte count, low glucose, low chloride and high cerebrospinal fluid protein. The median CD4 + T count of patients was 104 cells/μL (IQR, 36-224 cells/μL) at the onset of the disease. The CD4 + T cell counts of three patients who eventually died were significantly lower (W = 6.00, p = 0.020) than those of the patients who survived., Conclusions: The common clinical symptoms of T. marneffei central nervous system infection are associated with high intracranial pressure and intracranial infectious lesions. Earlier recognition and diagnosis and a prolonged course of amphotericin B treatment followed by itraconazole combined with early ART might reduce the mortality rate.

Knowledge about the clinical and laboratory characteristics and prognosis of Talaromyces marneffei infection in children is limited. A retrospective study was conducted on pediatric patients with disseminated T. marneffei infection in a clinical setting. Extracted data included demographic information (age and sex), clinical features, laboratory findings, treatment, and prognosis. Eleven HIV-negative children were enrolled. The male/female ratio was 8:3. The median age of onset was 17.5 months (3.5-84 months). The mortality rate in these children was 36.36% (4/11). Seven children had underlying diseases. All of the children had multiple immunoglobulin abnormalities and immune cell decline. Ten children received voriconazole treatment, and most of the children (7/10) had a complete response to therapy at primary and long-term follow-up assessment; only three children died of talaromycosis. One patient recovered from talaromycosis but died of leukemia. The child who received itraconazole treatment also showed clinical improvement. No adverse events associated with antifungal therapies were recorded during and after the treatment. Talaromycosis is an indicator disease for undiagnosed severe immunodeficiencies in children. Awareness of mycoses in children by pediatricians may prompt diagnosis and timely treatment. Voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection in non-HIV-infected children.

Background: A high proportion of men who have sex with men (MSM) use geosocial networking apps (Apps) to seek partners. However, the relationship of app use with HIV risk is unknown. Further, the risks of some sexually transmitted infection (STIs), including Mycoplasma genitalium, have seldom been studied among MSM., Methods: MSM were enrolled at a community-based HIV testing site in Shenyang, China. After completing a questionnaire survey, we collected rectal swabs and venous blood specimens. We then simultaneously tested for ten STIs (Chlamydia trachomatis [CT], Neisseria gonorrhea [NG], Ureaplasma urealyticum [Uu], Ureaplasma parvum species [Up1, Up3, Up6, Up14), Mycoplasma hominis [Mh], Mycoplasma genitalium [Mg], and Herpes Simplex Virus Type 2 (HSV-2) using multiple PCR. We also performed blood tests for HIV, Syphilis, Hepatitis C antibody (HCV-Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis A-IgM (HAV-IgM), etc. RESULTS: One hundred and eighty-three MSM participated in this study, of which 51.4% reported seeking partners through apps in the past year. The prevalence of HIV was 19.7%, Syphilis 12.0%, HAV 1.1%, rectal Mg 15.3% and Mh 7.1%. Multivariable logistic regression showed that HIV infection was independently correlated with app-using behavior (adjusted odds ratio[aOR] = 2.6), Mg infection (aOR = 3.2), Mh infection (aOR = 4.1) and Syphilis infection (aOR = 3.1) (each P < 0.05)., Conclusions: App use, Mg, Mh and Syphilis infection were correlated with higher HIV Risk in MSM. Geosocial networking apps should be utilized for HIV interventions targeting MSM. There is a need for more expansive STIs screening, particularly for Mg, Mh and Syphilis in MSM.

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4 + cell subgroups (<50 cells/μL, 50-99 cells/μL, 100-199 cells/μL), with the highest reduction observed in patients with a baseline CD4 + cell count <50 cells/μL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

Background: Talaromyces marneffei (T. marneffei) is a thermal dimorphic pathogenic fungus that often causes fatal opportunistic infections in human immunodeficiency virus (HIV)-infected patients. Although T. marneffei-infected cases have been increasingly reported among non-HIV-infected patients in recent years, no cases of T. marneffei infection have been reported in pulmonary sarcoidosis patients. In this case, we describe a T. marneffei infection in an HIV-negative patient diagnosed with pulmonary sarcoidosis., Case Presentation: A 41-year-old Chinese man who had pre-existing pulmonary sarcoidosis presented with daily hyperpyrexia and cough. Following a fungal culture from bronchoalveolar lavage (BAL), the patient was diagnosed with T. marneffei infection. A high-resolution computed tomography (HRCT) chest scan revealed bilateral lung diffuse miliary nodules, multiple patchy exudative shadows in the bilateral superior lobes and right inferior lobes, air bronchogram in the consolidation of the right superior lobe, multiple hilar and mediastinal lymphadenopathies and local pleural thickening. After 3 mos of antifungal therapy, the patient's pulmonary symptoms rapidly disappeared, and the physical condition improved markedly. A subsequent CT re-examination demonstrated that foci were absorbed remarkably after treatment. The patient is receiving follow-up therapy and assessment for a cure., Conclusion: This case suggested that clinicians should pay more attention to non-HIV-related lung infections in patients with pulmonary sarcoidosis. Early diagnosis and treatment with antifungal therapy can improve the prognosis of T. marneffei infection.

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis., Methods: Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit., Results: A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months' follow up., Conclusions: The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.

Genetic diversity of Pneumocystis jirovecii isolates based on internal transcribed spacer (ITS) of the nuclear rRNA locus has previously been reported. The information about ITS genotype and epidemiology of this organism in Chinese human immunodeficiency virus-infected patients has not been available. In this study, 12 bronchoalveolar lavage fluid specimens obtained from HIV-infected patients were analyzed by PCR followed by cloning, sequencing and typing. Three ITS1 genotypes (E, B and 'H') and four ITS2 genotypes (b, g, i and r) as previously reported were identified, the most common of which were E, b and i. Five ITS haplotypes (Eg, Eb, Bi, Er and 'H'r) and 19 new combination types were also identified with the most common types being Eg (four of 12 patients, 10 of 60 clones), Eb (three of 12 patients, 11 of 60 clones) and Bi (three of 12 patients, 10 of 60 clones). Nine patients were found to be co-infected with more than one ITS genotype of P. jirovecii. The prevalence of ITS genotypes in HIV patients from one Chinese hospital did not seem to be significantly different when compared to reports from other countries.

Cryptococcus spp. are common causes of mycoses in immunocompromised patients. To determine the drug susceptibilities of clinical Cryptococcus spp. isolates, the characteristics of 61 clinical Cryptococcus spp. complex isolates and their antifungal susceptibilities were investigated, including 52 C. neoformans and 9 C. gattii isolates collected at Shanghai between 1993 and 2009. Antifungal susceptibility of clinical isolates to amphotericin B, fluconazole, itraconazole, and flucytosine were determined by the microdilution method M27-A2 and the ATB FUNGUS 3 kit. The 90% minimum inhibitory concentration (MIC90) and susceptibility ranges were as follows: 1 (0.0625-1) µg/mL for amphotericin B, 4 (0.125-16) µg/ mL for fluconazole, 0.25 (0.0313-4) µg/mL for itraconazole, and 4 (0.125-8) µg/mL for flucytosine. Fluconazole, itraconazole, and flucytosine have excellent in vitro activity against all tested clinical Cryptococcus spp., and we also found a high rate of tolerance to amphotericin B (MICs ranging from 0.55-1 µg/mL). Furthermore, C. neoformans isolates from acquired immune deficiency syndrome (AIDS) patients were less susceptible to fluconazole and flucytosine than those from non-AIDS patients. These data suggest that use of amphotericin B may lead to tolerance or resistance of the pathogen over time. There were also no significant associations between species, genotypes, and in vitro susceptibilities of these clinical isolates.

The first case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identification was confirmed by rRNA amplification and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

Background: Penicillium marneffei is an opportunistic fungus that may cause fatal disease, and usually infects acquired immune deficiency syndrome (AIDS) patients. The molecular epidemiology of this fungus remains enigmatic., Methods: A multilocus microsatellite typing (MLMT) system based on 11 microsatellite loci was applied to 169 unrelated isolates of P. marneffei obtained from AIDS patients, in order to identify their genetic diversity. These patients came from the provinces of Guangdong and Guangxi, areas endemic for P. marneffei in China., Results: For the overall population, the average number of alleles per locus ranged from 3 to 8 (mean 5.5), while the discriminatory power (DP) of each locus ranged from 0.235 to 0.651 (mean 0.512). By combining the information generated for 11 loci, MLMT detected 159 different multilocus genotypes (MTs), resulting in a high degree of discrimination (DP = 0.999). One hundred and sixty-nine isolates were further clustered into 9 types (from A to I) at the similarity coefficient of 0.80, with type A (80 isolates) and type B (60 isolates) being the most common types. Within 5 subpopulations from different regions of China, the distribution of MTs of P. marneffei isolates was diverse. Although 169 isolates shared a high genetic similarity (range 0.71-0.933), isolates from Guangxi and Guangdong provinces could be differentiated from each other and clustered into 2 categories by unweighted pair-group method with arithmetic mean (UPGMA) cluster analysis., Conclusions: By MLMT, the genetic diversity of clinical P. marneffei isolates could be discriminated, the dominant strain of P. marneffei cultured from AIDS patients in China could be identified, and clinical isolates of P. marneffei from Guangxi Province could be differentiated from those from Guangdong Province.

Penicillium marneffei (PM) infection is prevalent in South-East Asia and Southern China and has been considered an acquired immunodeficiency syndrome (AIDS)-defining disease. This report focused on the verrucoid proliferative lesions of P. marneffei infection in a 34-year-old Chinese female AIDS patient from a non-endemic region. She recovered after receiving intravenous amphotericin B followed by oral itraconazole therapy. At the same time, highly active antiretroviral therapy (HAART) was also started. She responded very well to the treatment.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are associated with failure of sulfur prophylaxis of Pneumocystis pneumonia. Here the P. jirovecii DHPS gene was amplified from bronchoalveolar fluid of 10 AIDS patients in China. No DHPS gene mutations were observed. The results suggest that the prevalence of DHPS mutations in China may be low.

To determine the population structure of the cryptococcosis agents in China, we analyzed the genotype of 120 Cryptococcus neoformans and 9 Cryptococcus gattii strains isolated from 1980 through 2006 from cryptococcosis patients residing in 16 provinces of mainland China. A total of 71% (91/129) of the clinical strains isolated from 1985 through 2006 were from patients without any apparent risk factors. Only 8.5% (11/129) were from AIDS patients; the remaining 20.5% (27/129) were from patients with underlying diseases other than HIV infection. One hundred twenty of the 129 isolates were C. neoformans serotype A, mating type MATalpha strains that exhibited an identical M13-based VNI subtype, which was distinguishable from the reference VNI molecular type. The 9 remaining isolates were serotype B, MATalpha strains of C. gattii and portrayed a typical VGI molecular type. Data analyzed from multilocus sequences showed no variation and that these Chinese C. neoformans isolates belong to a cluster that has phylogenetically diverged from the VNI reference strain. Our finding that most cryptococcosis patients in China had no apparent risk factor is in stark contrast with reports from other countries.

Aim: To compare the prevalence of H pylori infection, peptic ulcer, cytomegalovirus (CMV) infection and Candida esophagitis in human immunodeficiency virus (HIV)-positive and HIV-negative patients, and evaluate the impact of CD4 lymphocyte on H pylori and opportunistic infections., Methods: A total of 151 patients (122 HIV-positive and 29 HIV-negative) with gastrointestinal symptoms were examined by upper endoscopy and biopsy. Samples were assessed to determine the prevalence of H pylori infection, CMV, candida esophagitis and histologic chronic gastritis., Results: The prevalence of H pylori was less common in HIV-positive patients (22.1%) than in HIV-negative controls (44.8%; P < 0.05), and the prevalence of H pylori displayed a direct correlation with CD4 count stratification in HIV-positive patients. In comparison with HIV-negative group, HIV-positive patients had a lower incidence of peptic ulcer (20.7% vs 4.1%; P < 0.01), but a higher prevalence of chronic atrophy gastritis (6.9% vs 24.6%; P < 0.05)ìCandida esophagitis and CMV infection. Unlike HIV-negative group, H pylori infection had a close relationship to chronic active gastritis (P < 0.05). In HIV-positive patients, chronic active gastritis was not significantly different between those with H pylori infection and those without., Conclusion: The lower prevalence of H pylori infection and peptic ulcer in HIV-positive patients with gastrointestinal symptoms suggests a different mechanism of peptic ulcerogenesis and a different role of H pylori infection in chronic active gastritis and peptic ulcer. The pathogen of chronic active gastritis in HIV-positive patients may be different from the general population that is closely related to H pylori infection.

Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.

This study of Pneumocystis carinii dihydropteroate synthase (DHPS) mutations in patients with AIDS who have P. carinii pneumonia compares the change in the prevalence of such mutations in the United States, where sulfa-drug prophylaxis is widespread, to that in China, where it is infrequent. The DHPS gene from 145 US patients presenting during 1983-2001 and from 15 Chinese patients presenting during 1998-2001 was amplified by polymerase chain reaction and was sequenced. In the United States, 40% of patients had DHPS mutations; 38% received sulfa-drug prophylaxis. Mutation prevalence increased to 70% during 2000-2001, from 25% during 1994-1995 (P<.01). In China, 7% of patients had DHPS mutations; none received sulfa-drug prophylaxis. The prevalence of P. carinii DHPS mutations has markedly increased in the United States but remains low in China.

A variety of innate defense factors in saliva such as lysozyme and lactoferrin contribute to mucosal protection and modulate Candida populations in the oral cavity. It is also known that in human immunodeficiency virus (HIV)-infected individuals significant variations in the concentrations of lysozyme and lactoferrin in saliva occur during disease progression. Therefore, the aim of this study was to determine the in vitro susceptibility to human lactoferrin and hen egg white lysozyme of genotypically similar oral Candida albicans isolates obtained from six HIV-infected ethnic Chinese during sequential visits over a 12-month period. The similarity of the genotypes (50 in total) was evaluated using a randomly amplified polymorphic DNA assay. A blastospore viability assay was performed to evaluate the sensitivity of the organisms to lysozyme and lactoferrin. Exposure to physiological concentrations of either lysozyme (30 microg/ml) or lactoferrin (20 microg/ml) caused a rapid loss of viability among all isolates to a varying extent. None of the sequential C. albicans isolates demonstrated significant differences in sensitivity to either protein from one visit to the next; similar results were noted when the different genotypes from the same individual were compared. On Spearman correlation analysis of two genotypes that were sequentially isolated from a single patient, a significant negative correlation between lysozyme (r = -0.88; P < 0.02) (but not lactoferrin) resistance and the duration of HIV disease was seen. These results imply that a minority of C. albicans isolates that persist intraorally in individuals with HIV disease develop progressive resistance to innate salivary antifungal defenses such as lysozyme, possibly as an adaptive response. However, the vast majority of the Candida isolates appear to succumb to these nonspecific host immune mediators abundantly present in the oral environment.

The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml, <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage--44%(7/16)--exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.

Objective: The aim of this study was to improve the awareness of pulmonary complications in patients with AIDS., Methodology: Nine patients with AIDS with pulmonary involvement from March 1992 to March 2000 were analysed., Results: Of the nine cases, there were eight cases complicated with Pneumocystis carinii pneumonia (PCP). The clinical presentation of PCP was fever (8/8), dyspnoea on exertion or at rest (7/8), and hypoxaemia with a mean PaO2 of 58 mmHg. Chest X-ray films showed bilateral diffuse interstitial or alveolar infiltrates. Pulmonary tuberculosis, tuberculous lymphadenitis and bronchial fungal infection were found in three cases., Conclusions: AIDS patients are at high risk of suffering from pulmonary complications, of which PCP is most common. If young patients who were healthy in the past suddenly suffered from pneumonia and respiratory failure, PCP should be considered. When opportunistic pulmonary infection is diagnosed under special circumstances, one should be alert to the possibility of AIDS and examine serum antihuman immunodeficiency virus (HIV) antibody.

Penicillium marneffei has emerged as an important opportunistic pathogen in HIV-infected patients in Southeast Asia. We report the first 5 cases of P. marneffei diagnosed in Singapore. All the patients were HIV-infected and were either Thai nationals or had frequently travelled to Thailand. Fever, weight loss, anaemia and papular skin lesions were common clinical manifestations in our patients, all of whom had the organism isolated from blood. Skin biopsy specimens showed histological evidence of P. marneffei in 2 patients. In 1 patient each, the organism grew in cultures of specimens from bone marrow and respiratory secretions. Amphotericin B therapy followed by itraconazole were used in 3 of our 5 patients and was associated with good clinical response and outcome.

Opportunistic infections are major causes of morbidity in patients with human immunodeficiency virus (HIV) infection. Penicillium marneffei infection is very common in HIV-infected individuals in northern Thailand. The patients usually present with fever, anemia, weight loss, skin lesions, generalized lymphadenopathy, and hepatomegaly. The average number of CD4+ T-lymphocytes at presentation was 63.8 cells/mm3. Diagnosis depends on familiarity with the clinical syndromes and support from the mycology laboratory. The response to antifungal treatment of the patients is generally good, but depends on the ability of the physician to make the diagnosis and start the treatment early. New approaches to the laboratory diagnosis of P. marneffei infection have been reported. Further study of these approaches may help physicians in taking better care of the patients.

Penicillium marneffei is endemic in Southeast Asia, the Guangxi province of China, and Hong Kong. Cases of patients infected with P. marneffei have been very rare, but the incidence has increased markedly during the past several years. This increase is exclusively due to infection among patients infected with human immunodeficiency virus (HIV). The patients usually presented with symptoms and signs similar to other patients with late HIV diseases. These included fever (99% of the patients), anaemia (78%), pronounced weight loss (76%), generalised lymphadenopathy (58%) and hepatomegaly (51%). Skin lesions were seen in 71% of our patients. These lesions were most commonly papules with central necrotic umbilication. It was easy to culture P. marneffei from various clinical specimens. Bone marrow culture was the most sensitive (100%), followed by culture of the specimen obtained from skin biopsy (90%) and blood culture (76%). The fungus was sensitive to amphotericin B, itraconazole, and ketoconazole. Our regimen is to give amphotericin B for 2 weeks, followed by itraconazole 400 mg/day orally for the next 10 weeks. After the initial treatment, the patient is given itraconazole 200 mg/day as secondary prophylaxis for life.