Displaying publications 1 - 20 of 34 in total

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  1. Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.
    Eur J Clin Microbiol Infect Dis, 2019 Dec;38(12):2349-2353.
    PMID: 31529307 DOI: 10.1007/s10096-019-03699-5
    Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.
  2. Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.
    Pathog Glob Health, 2020 03;114(2):99-103.
    PMID: 32024441 DOI: 10.1080/20477724.2020.1724356
    Leptospirosis causes a wide range of clinical outcomes, including organ failure and death. Early treatment significantly increases the chances of cure. Interleukin-8 (IL-8) is a chemoattractant cytokine for neutrophil and is associated with multiple organ failure. Research has indicated IL-8 to be raised in severe and fatal cases of leptospirosis, but its suitability as a prognostic biomarker has yet to be confirmed. This study aimed to evaluate the significance of IL-8 with the clinical outcomes of leptospirosis patients. Plasma IL-8 was measured in fifty-two samples from hospitalized patients and nineteen healthy controls. The comparisons were made between mild, severe-survived and fatal groups identified by clinical or laboratory findings. IL-8 was significantly higher in fatal (p = 0.01) compared to mild cases. IL-8 was also significantly higher in fatal (p = 0.02) when compared to survived cases of leptospirosis. IL-8 levels in the plasma of fatal leptospirosis cases were significantly elevated compared to survived cases and may serve as a potential prognostic biomarker in determining the possible outcome of leptospirosis patients.
  3. Vincent AT, Schiettekatte O, Goarant C, Neela VK, Bernet E, Thibeaux R, et al.
    PLoS Negl Trop Dis, 2019 05;13(5):e0007270.
    PMID: 31120895 DOI: 10.1371/journal.pntd.0007270
    The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the natural environment contaminated with the urine of a wide range of reservoir animals. Soils and surface waters also host a high diversity of non-pathogenic Leptospira and species for which the virulence status is not clearly established. The genus Leptospira is currently divided into 35 species classified into three phylogenetic clusters, which supposedly correlate with the virulence of the bacteria. In this study, a total of 90 Leptospira strains isolated from different environments worldwide including Japan, Malaysia, New Caledonia, Algeria, mainland France, and the island of Mayotte in the Indian Ocean were sequenced. A comparison of average nucleotide identity (ANI) values of genomes of the 90 isolates and representative genomes of known species revealed 30 new Leptospira species. These data also supported the existence of two clades and 4 subclades. To avoid classification that strongly implies assumption on the virulence status of the lineages, we called them P1, P2, S1, S2. One of these subclades has not yet been described and is composed of Leptospira idonii and 4 novel species that are phylogenetically related to the saprophytes. We then investigated genome diversity and evolutionary relationships among members of the genus Leptospira by studying the pangenome and core gene sets. Our data enable the identification of genome features, genes and domains that are important for each subclade, thereby laying the foundation for refining the classification of this complex bacterial genus. We also shed light on atypical genomic features of a group of species that includes the species often associated with human infection, suggesting a specific and ongoing evolution of this group of species that will require more attention. In conclusion, we have uncovered a massive species diversity and revealed a novel subclade in environmental samples collected worldwide and we have redefined the classification of species in the genus. The implication of several new potentially infectious Leptospira species for human and animal health remains to be determined but our data also provide new insights into the emergence of virulence in the pathogenic species.
  4. 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.
  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. Shamsusah NA, Agustar HK, Amran F, Hod R
    Microbiol Resour Announc, 2021 Sep 30;10(39):e0072321.
    PMID: 34591676 DOI: 10.1128/MRA.00723-21
    Previously, a novel Leptospira strain (BJ3) was isolated from the soil of an ex situ wild animal conservation area in Perak, Malaysia. Molecular identification via whole-genome sequencing confirmed that the strain was Leptospira yasudae. Here, we report the draft genome sequence of L. yasudae strain BJ3.
  7. Riazi M, Zainul FZ, Bahaman AR, Amran F, Khalilpour A
    Indian J Med Res, 2014 Feb;139(2):308-13.
    PMID: 24718408
    Leptospirosis is a widespread zoonotic disease and a public health problem, particularly in tropical and subtropical countries. Varied clinical manifestations of the disease frequently lead to misdiagnosis resulting in life-threatening multi-organ complications. Therefore, early laboratory investigation using an appropriate diagnostic approach is crucial. In the present study, a potential protein marker was identified and evaluated for its usefulness in the serodiagnosis of acute leptospirosis.
  8. Rao M, Amran F, Kamaruzaman AA, Hakim Esa HA, Abdul Hameed A, Mohamed Shabery NA
    Am J Trop Med Hyg, 2021 01;104(1):216-218.
    PMID: 33289472 DOI: 10.4269/ajtmh.20-0267
    Leptospirosis is an important zoonotic disease with worldwide distribution and nonspecific clinical manifestation. We report a case of fatal leptospirosis in a previously healthy woman with a causative agent. A young adult Indian woman was brought in dead to the forensic department. Ten days before, she developed fever, dizziness with headache, myalgia, diarrhea, and vomiting. Routine inquest and autopsy were performed on the deceased, revealing hemorrhagic lungs with extensive intra-alveolar hemorrhages, pale liver with dissociation and separation of hepatocyte plates, and edematous brain with histiocyte and lymphocyte infiltration in the parenchyma and meninges. Heart tissue depicts myocarditis and pericarditis inflammatory changes. Cerebrospinal fluid (CSF) was turbid in appearance with mildly elevated leukocytes, predominantly lymphocytes. Real-time PCR targeting lipL32 gene of pathogenic Leptospira was detected in the blood, CSF, brain, kidney, heart, and liver. The genetic profile of the causative agent was ST149 (multi-locus sequence typing Scheme 3). This study illustrates the usefulness of Leptospira PCR assay in postmortem diagnosis and addresses the need for further surveillance to identify the epidemiological link of the disease.
  9. Rao M, Rashid FA, Sabri FSAH, Jamil NN, Zain R, Hashim R, et al.
    Clin Infect Dis, 2021 05 04;72(9):e352-e356.
    PMID: 32761244 DOI: 10.1093/cid/ciaa1156
    BACKGROUND: The ideal severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) testing method would be accurate and also be patient-performed to reduce exposure to healthcare workers. The aim of this study was to compare patient-performed testing based on a morning saliva sample with the current standard testing method, healthcare worker-collected sampling via a nasopharyngeal swab (NPS).

    METHODS: This was a prospective single center study which recruited 217 asymptomatic adult male participants in a coronavirus disease 2019 (COVID-19) quarantine center who had tested positive for SARS-CoV-2 8-10 days prior to isolation. Paired NPS and saliva specimens were collected and processed within 5 hours of sample collection. Real time reverse transcription polymerase chain reaction (RT-PCR) targeting Envelope (E) and RNA-dependent RNA polymerase (RdRp) genes was performed and the results were compared.

    RESULTS: Overall, 160 of the 217 (74%) participants tested positive for COVID-19 based on saliva, NPS, or both testing methods. The detection rate for SARS-CoV-2 was higher in saliva compared to NPS testing (93.1%, 149/160 vs 52.5%, 84/160, P < .001). The concordance between the 2 tests was 45.6% (virus was detected in both saliva and NPS in 73/160), whereas 47.5% were discordant (87/160 tested positive for 1 whereas negative for the other). The cycle threshold (Ct) values for E and RdRp genes were significantly lower in saliva specimens compared to NP swab specimens.

    CONCLUSIONS: Our findings demonstrate that saliva is a better alternative specimen for detection of SARS-CoV-2. Taking into consideration, the simplicity of specimen collection, shortage of PPE and the transmissibility of the virus, saliva could enable self-collection for an accurate SARS-CoV-2 surveillance testing.

  10. Rao M, Atiqah N, Dasiman M, Amran F
    J Med Microbiol, 2020 Mar;69(3):451-456.
    PMID: 31846413 DOI: 10.1099/jmm.0.001127
    Introduction. Co-infection of leptospirosis-malaria is not uncommon due to their overlapping geographical distribution in the tropics.Aim. This study aimed to describe and compare the demographic, clinical and laboratory features of leptospirosis-malaria co-infection (LMCI) against leptospirosis mono-infection (LMI) in Peninsular Malaysia.Methodology. Data of patients admitted to various hospitals in Peninsular Malaysia from 2011 to 2014 diagnosed with leptospirosis in our laboratory were obtained from their admission records. Co-infections with malaria were identified via blood film for malaria parasites (BFMP). Description with inferential statistics analysis and multiple logistic regressions were used to distinguish features between dual and mono-infections.Results. Of 111 leptospirosis-positive patients, 26 (23.4 %) tested positive for malaria. Co-infections were predominant among male patients with a mean age of 33 years and were prevalent among immigrant populations who had settled in high-density suburban areas. Chills and rigor with splenomegaly were the only significant distinguishing clinical features of LMCI while leukocytosis and raised transaminases were significant laboratory parameters. Only chills and rigor demonstrated a predictive value for LMCI from analysis of multiple logistic regressions. No death was attributed to co-infection in this study, in contrast to LMI (11.8 %, n=10).Conclusion. The significant prevalence of LMCI found in this study with overlapping demographic, clinical and laboratory parameters makes diagnosis of co-infection challenging. It is essential to evaluate co-infection in endemic areas. Strengthened awareness of LMCI, comprehensive diagnostic services and further prospective studies are warranted.
  11. Rao M, Amran F, Aqilla N
    Can J Infect Dis Med Microbiol, 2019;2019:5763595.
    PMID: 30881530 DOI: 10.1155/2019/5763595
    Introduction: Leptospirosis is an acute febrile illness, known for its protean clinical manifestations and the challenge in differentiating from other infectious diseases. Standardized confirmatory test is antibody dependent and not accessible by the suburban community. This study measures efficiency of an immune-chromatographic assay, Leptocheck WB, in detecting acute leptospirosis.

    Methods: A total of 142 sera were used for kit evaluation. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated by comparing rapid kit results with gold standard laboratory, microscopic agglutination test (MAT).

    Results: We found this rapid kit to have a sensitivity and specificity of 66.6% and 78.9%, respectively, whereas the PPV and NPV of the kit appeared to be 73.3% and 73.2%, respectively.

    Discussion: Test efficiency of this rapid kit is reasonable. It is specific in detecting leptospiral antibody and assures clinician of accurate diagnosis by having higher PPV and NPV. It is prompt and efficient in comparison with conventional methods in assisting differential diagnosis. High sensitivity and specificity leptospirosis rapid test is indeed a crucial measure to assist the diagnosis of acute undifferentiated febrile illnesses.

  12. Rao M, Rashid FA, Sabri FSAH, Jamil NN, Seradja V, Abdullah NA, et al.
    J Med Virol, 2021 Apr;93(4):2461-2466.
    PMID: 33393672 DOI: 10.1002/jmv.26773
    An optimal clinical specimen for accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by minimizing the usage of consumables and reduce hazard exposure to healthcare workers is an urgent priority. The diagnostic performance of SARS-CoV-2 detection between healthcare worker-collected nasopharyngeal and oropharyngeal (NP + OP) swabs and patient performed self-collected random saliva was assessed. Paired NP + OP swabs and random saliva were collected and processed within 48 h of specimen collection from two cohort studies which recruited 562 asymptomatic adult candidates. Real-time reverse-transcription polymerase chain reaction targeting Open reading frame 1a (ORF1a) and nucleocapsid (N) genes was performed and the results were compared. Overall, 65 of 562 (28.1%) candidates tested positive for COVID-19 based on random saliva, NP + OP swabs, or both testing techniques. The detection rate of SARS-CoV-2 was higher in random saliva compared to NP + OP testing (92.3%; 60/65 vs. 73.8%; 48/65; p 
  13. Rajandran S, Razali KM, Mustapha M, Palaniappan PA, Amran F
    Case Rep Ophthalmol Med, 2020;2020:5861258.
    PMID: 32774963 DOI: 10.1155/2020/5861258
    Cyphellophora is a black yeast-like fungus with most of the strains being isolated from soil and plants. It tends to cause sooty blotch and flyspeck disease in plants. In humans, it is known to cause superficial skin and nail infections. This report highlights the case of a patient who initially presented with a small corneal abrasion which rapidly progressed into a corneal ulcer after the patient did not respond to the initial conventional treatment. The laboratory results from the corneal scraping found it to be Cyphellophora sp.
  14. Palaniappan PA, Abot CA, Mohd Tap R, Amran F
    IDCases, 2021;24:e01121.
    PMID: 33912392 DOI: 10.1016/j.idcr.2021.e01121
    Prototheca species have been reported to cause infections in human. Typically, clinical symptoms of protothecosis include cutaneous infection, olecranon bursitis, tenosynovitis and disseminated systemic disease. We report a case of septic arthritis in which Prototheca zopfii was isolated from blood. Joint aspirate was also sent for cultures but did not yield any growth. No other organisms were isolated from this patient during his admission. The blood isolate was identified to species level via Polymerase Chain Reaction (PCR) method. The patient improved with administration of intravenous itraconazole.
  15. Othman N, Intan HI, Yip CW, Alias M, Amran F
    J Trop Pediatr, 2007 Feb;53(1):55-8.
    PMID: 17237115
    We report a case of an 8-year-old aborigine boy referred to our hospital for respiratory insufficiency with skin eruptions over the trunk and limbs. The skin condition was diagnosed as acquired ichthyosis. He also had a non-bleeding form of disseminated intravascular coagulopathy. Radiograph of the lungs showed bilateral perihilar opacities with bilateral pleural effusion. The diagnosis of leptospirosis was confirmed by a 4-fold rise in microagglutinating titre and polymerase chain reaction assay.
  16. Othman N, Yip CW, Intan HI, Zainuddin Z, Amran F
    Ann Trop Paediatr, 2006 Sep;26(3):259-62.
    PMID: 16925966
    A 7-year-old boy, referred with lymphoma, presented with prolonged fever and intra-abdominal lymphadenopathy demonstrated on computed tomography (CT) of the abdomen. Blood culture isolated Penicillium marneffei. The patient was subsequently proven serologically to be positive for human immunodeficiency virus (HIV). Treatment with amphotericin B followed by itraconazole was successful. A high level of clinical suspicion and awareness is necessary for early diagnosis of penicilliosis, especially in an era of an increasing prevalence of HIV in this region.
  17. Noh MA, Masri SN, Zulkapli A, Mohd Ali MR, Amran F
    J Vector Borne Dis, 2024 Jan 01;61(1):43-50.
    PMID: 38648405 DOI: 10.4103/0972-9062.383644
    BACKGROUND OBJECTIVES: Leptospirosis is an important zoonotic infection that has caused significant mortality and morbidity worldwide. This disease is endemic in Malaysia and as a developing tropical country, leptospirosis is concerning as it threatens Malaysian public health and the country's economic sectors. However, there is limited information on leptospirosis in Malaysia, especially regarding leptospiral seroepidemiology among carriers in Malaysia. Therefore, more epidemiological information on the source of the disease and reservoir are needed for better disease control and source intervention. The objectives of this study are to gather information on Leptospira infection and the carrier status of rats captured from selected wet markets of Kuala Lumpur metropolitan city in Malaysia.

    METHODS: Live rat trappings were performed in four major wet markets in Kuala Lumpur, namely, Pudu, Chow Kit, Datuk Keramat, and Petaling Street. Animal samplings were performed for 12 months in 2017, where blood and kidney samples were collected and tested for anti-leptospiral antibodies via Microscopic Agglutination Test (MAT) and pathogenic Leptospira screening via Polymerase Chain Reaction (PCR) amplification offlaB gene.

    RESULTS: MAT showed that 34.7% (n = 50/144) of the captured rats were positive for anti-leptospiral antibody of which the most prominent serovar was Malaya followed by a local strain, IMR LEP 175. In parallel, 50 rats were also positive for pathogenic Leptospira DNA.

    INTERPRETATION CONCLUSION: This study showed that there are persistent Leptospira infections among rats in Kuala Lumpur wet markets and these rats are important reservoir hosts for the bacteria.

  18. Mohd Tap R, Kamarudin NA, Ginsapu SJ, Ahmed Bakri AR, Ahmad N, Amran F, et al.
    Genome Announc, 2018 Apr 05;6(14).
    PMID: 29622608 DOI: 10.1128/genomeA.00166-18
    Candida pseudohaemulonii is phylogenetically close to the C. haemulonii complex and exhibits resistance to amphotericin B and azole agents. We report here the draft genome sequence of C. pseudohaemulonii UZ153_17 isolated from the blood culture of a neutropenic patient. The draft genome is 3,532,003,666 bp in length, with 579,838 reads, 130 contigs, and a G+C content of 47.15%.
  19. Mohd Tap R, Lim TC, Kamarudin NA, Ginsapu SJ, Abd Razak MF, Ahmad N, et al.
    Mycopathologia, 2018 Jun;183(3):559-564.
    PMID: 29383574 DOI: 10.1007/s11046-018-0244-y
    We report a fatal case of Candida auris that was involved in mixed candidemia with Candida tropicalis, isolated from the blood of a neutropenic patient. Identification of both isolates was confirmed by amplification and sequencing of internal transcribed spacer and D1/D2 domain of large subunit in rRNA gene. Antifungal susceptibility test by E-test method revealed that C. auris was resistant to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole and voriconazole. On the other hand, C. tropicalis was sensitive to all antifungal tested. The use of chromogenic agar as isolation media is vital in detecting mixed candidemia.
  20. Mohd Ali MR, Sum JS, Aminuddin Baki NN, Choong YS, Nor Amdan NA, Amran F, et al.
    Int J Biol Macromol, 2021 Jan 31;168:289-300.
    PMID: 33310091 DOI: 10.1016/j.ijbiomac.2020.12.062
    Leptospirosis is a potentially fatal zoonosis that is caused by spirochete Leptospira. The signs and symptoms of leptospirosis are usually varied, allowing it to be mistaken for other causes of acute febrile syndromes. Thus, early diagnosis and identification of a specific agent in clinical samples is crucial for effective treatment. This study was aimed to develop specific monoclonal antibodies against LipL21 antigen for future use in leptospirosis rapid and accurate immunoassay. A recombinant LipL21 (rLipL21) antigen was optimized for expression and evaluated for immunogenicity. Then, a naïve phage antibody library was utilized to identify single chain fragment variable (scFv) clones against the rLipL21 antigen. A total of 47 clones were analysed through monoclonal phage ELISA. However, after taking into consideration the background OD405 values, only 4 clones were sent for sequencing to determine human germline sequences. The sequence analysis showed that all 4 clones are identical. The in silico analysis of scFv-lip-1 complex indicated that the charged residues of scFv CDRs are responsible for the recognition with rLipL21 epitopes. The generated monoclonal antibody against rLipL21 will be evaluated as a detection reagent for the diagnosis of human leptospirosis in a future study.
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