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  1. Yeow YY, Tan XT, Low LL
    Infect Dis Rep, 2023 Feb 03;15(1):102-111.
    PMID: 36826351 DOI: 10.3390/idr15010011
    BACKGROUND: Sporotrichosis is a subacute or chronic mycosis caused by a dimorphic fungus of the genus Sporothrix. Zoonotic-transmitted sporotrichosis has become a major public health concern and is characterised by a different clinical pattern from the traditional epidemiology of sporotrichosis.

    CASE PRESENTATION: We present the details of four patients with mucosal sporotrichosis with regional lymphadenopathy (three cases of granulomatous conjunctivitis and one case of nasal sporotrichosis). The patients' age range was between 23 to 46 years old and their gender was three female and one male patient. All four patients shared the same ethnicity, Malay, and they had a common history of owning domestic cats as pets. Sporothrix schenckii were isolated from all the culture samples and its antifungal susceptibility patterns were compared in the mycelial and yeast phases. All four patients recovered with oral itraconazole treatment, but the treatment duration was variable among patients.

    CONCLUSIONS: People who have a history of contact with domestic cats should be aware of the possibility of sporotrichosis infection. It can present in cutaneous, lymphocutaneous, disseminated, or systemic forms. Early treatment and the prevention of disease progression are more beneficial to patients. The published data concludes that antifungal treatment is highly efficacious, although the reported treatment duration is variable.

  2. Tan XT, Amran F, Chee Cheong K, Ahmad N
    BMC Infect Dis, 2014;14:563.
    PMID: 25338815 DOI: 10.1186/s12879-014-0563-7
    Leptospirosis is a zoonotic disease caused by Leptospira species and is distributed globally. Microscopic agglutination test (MAT) is the serological 'gold standard' for diagnosis of leptospirosis but it is time-consuming and labour-intensive. An alternative serological method that is rapid, sensitive and specific is important for early treatment to reduce morbidity and mortality. The use of local Leptospira isolation may improve the sensitivity and specificity of the test because it may varies from one geographical region to another region. The objective of this study was to determine the sensitivity, specificity and cut-off points for an in-house Immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) using a locally isolated Leptospiral strain IMR/175 as the antigen for the detection of anti-Leptospiral IgM.
  3. Tan XT, Mokhtar NNB, Hii SYF, Amran F
    Infect Drug Resist, 2024;17:2159-2168.
    PMID: 38828376 DOI: 10.2147/IDR.S452619
    PURPOSE: Azole resistance in Aspergillus fumigatus poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and cyp51A mutation profiles of A. fumigatus isolates in Malaysia.

    PATIENTS AND METHODS: Sixty clinical A. fumigatus isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC50/MIC90 for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against A. fumigatus in non-invasive cases and invasive cases were calculated. In addition, the presence of cyp51A mutations was also identified.

    RESULTS: The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various cyp51A mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance.

    CONCLUSION: The majority of clinical Aspergillus fumigatus isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, cyp51A mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.

  4. Tan XT, Mohd Shuhairi NB, Mohd Tap R, Amran F
    Indian J Med Microbiol, 2024 Jul 05;50:100663.
    PMID: 38964501 DOI: 10.1016/j.ijmmb.2024.100663
    PURPOSE: Candida albicans is the second most common cause of candidemia in Malaysia. The Clinical and Laboratory Standards Institute (CLSI) broth microdilution method is the gold standard for determining its minimum inhibitory concentration (MIC); however, it is laborious and time-consuming. This study was conducted to evaluate the usefulness of alternative methods, namely Sensititre YeastOne (SYO), VITEK 2 system, and E-test for determining the MIC of clinical C. albicans isolates.

    MATERIALS AND METHODS: The susceptibilities of 95 C. albicans isolates were compared between SYO, VITEK 2 system, and E-test with CLSI broth microdilution method. The categorical agreement (CA), essential agreement (EA), very major errors (VME), major errors (ME) and minor errors (MiE) were calculated.

    RESULTS: Our finding showed the CA varied for SYO from 96.8% to 100%, while the EA ranged from 91.6% to 100%. The SYO method showed 1.1% of VME and ME, and up to 3.2% of MiE. Next, the CA and EA ranges for the VITEK 2 system were 97.8%-100% and 23.2%-100%, respectively. In the VITEK 2 technique, 1.1% of VME were found. For the E-test, the CA varied from 83.2% to 100% while the EA ranged from 64.2% to 98.9%. The E-test method showed 1.1% of VME and up to 16.8% of MiE.

    CONCLUSIONS: In conclusion, SYO and VITEK 2 (except flucytosine) could be potential alternatives to the CLSI broth microdilution method in determining the MIC of C. albicans.

  5. Tan XT, Binti Mohd Shuhairi N, Jane Ginsapu S, Binti Shukor S, Amran F
    Infect Drug Resist, 2023;16:1629-1635.
    PMID: 36987447 DOI: 10.2147/IDR.S398743
    PURPOSE: This study was aimed to determine minimum inhibitory concentration (MIC) differences between yeast and mold forms of T. marneffei in Malaysia.

    PATIENTS AND METHODS: Ninety-seven clinical strains of T. marneffei were received from various Malaysian hospitals from the year 2020 until 2022. Their identities were determined using microscopic, macroscopic and molecular methods. Next, the susceptibility of yeast and mold forms of each isolate against amphotericin B, itraconazole, voriconazole, posaconazole, ketoconazole, isavuconazole, terbinafine, caspofungin and micafungin were tested according to the broth microdilution according to the Clinical and Laboratory Standards Institute (CLSI) M38 and M27 guidelines. The geometric means of minimal inhibitory concentration (GM MIC), MIC50, and MIC90 were determined for each antifungal. Additionally, Wilcoxon signed-rank test was used to compare the significant difference of GM MICs for each antifungal, GM MIC, MIC50 and MIC90 for the combined nine antifungals against different growth forms of T. marneffei. The significance was set at p<0.05.

    RESULTS: Micafungin had the highest GM MIC, MIC50 and MIC90 for mold form of T. marneffei. For yeast form, amphotericin B achieved the highest GM MIC and MIC50 while micafungin achieved the highest MIC90. However, the GM MIC, MIC50 and MIC90 of terbinafine and azole antifungals on T. marneffei were similar to each other, namely between 0.03 and 0.60µg/mL. The difference of GM MIC of all tested antifungals except caspofungin and micafungin was insignificant. Overall, GM MIC, MIC50 and MIC90 of the combined nine antifungals against two growth forms were insignificant.

    CONCLUSION: The findings suggested either yeast or mold form can be used in the susceptibility testing of T. marneffei against amphotericin B, itraconazole, voriconazole, posaconazole, ketoconazole, isavuconazole and terbinafine.

  6. Ng LC, Lee CS, Lim BB, Mohd Tap R, Tan XT, Tang MM
    Med J Malaysia, 2023 May;78(3):364-371.
    PMID: 37271847
    INTRODUCTION: Dermatomycoses are common superficial cutaneous fungal infections which affect the skin, nails and human hairs. It affects 20 to 25% of the world population. The causative fungus varies geographically across the globe. Study on dermatomycoses is crucial to identify the aetiological fungus involved locally. The study aimed to determine the causative fungus of superficial fungal infections of the skin, nail and hair in patients presented to Hospital Melaka.

    METHODS: This was a prospective study conducted from 15th January 2022 till 15th October 2022 at Dermatology Clinic, Hospital Melaka. Subjects with clinical dermatomycoses were included in this study. The samples were collected from skin, nails and hairs clinically affected by tinea corporis/cruris/pedis, onychomycosis and tinea capitis respectively. A potassium hydroxide (KOH) study was performed on the sample in which the fungal hyphae/yeast positive subjects were sent for fungal culture and fungal PCR test.

    RESULT: A total of 222 clinical samples from skin, nails and hairs with a clinical suspicion of dermatomycoses yielded fungal hyphae/yeast in KOH. Majority of the samples were collected from skin (138, 62.2%), followed by nails (65, 29.3%) and hairs (19, 8.6%). Male to female ratio was 1.18: 1. The age ranged from 2 to 87 with the median of 55.5-yearsold. Out of 222 samples, 150 (67.6%) were fungal culture positive. From fungal culture positive samples, 87 samples were from tinea corporis, 50 samples were from onychomycoses and 13 samples were from tinea capitis. Trichophyton rubrum (39, 44.8%) was the commonest dermatophyte isolated in tinea corporis/cruris/pedis. Nondermatophyte moulds (NDM, 35, 70%) were the main fungi isolated in onychomycosis. Microsporum canis (7/53.8%) was the principal causative fungus among patients with tinea capitis. Among 150 fungal culture positive samples, 76 were fungal PCR positive. Only 38 samples consistently isolated same fungal species in both fungal culture and PCR test.

    CONCLUSION: Majority of tinea corporis and tinea capitis fungal culture isolated dermatophytes, especially Trichophyton rubrum and Microsporum canis, respectively. Non-dermatophyte moulds were mainly isolated in onychomycosis.

  7. Tan XT, Amran FB, Thayan R, Ahmad N, Jaafar R, Haron R, et al.
    Electrophoresis, 2017 09;38(17):2141-2149.
    PMID: 28524240 DOI: 10.1002/elps.201600471
    Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild nonspecific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, 15 paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS. The expression of proteins that were significantly different and had a fold difference of at least 2 had been identified and then validated using Western blot. Our study demonstrated apolipoprotein A-I (APOA-I), serum amyloid A (SAA), transferrin (TF), haptoglobin (HP) and transthyretin (TTR) have significantly different expression between mild and severe leptospirosis. The Ingenuity Pathway Analysis software suggested the expression of these five proteins were modulated by acute phase response signaling pathway. Besides that, a functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects these five proteins with interactomes also had been predicted by this software. In conclusion, this finding supports the potential of these five proteins to be the biomarkers for mild and severe human leptospirosis.
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