Publications by authors named "Yupin Suputtamongkol"

66 Publications

Comparative genome characterization of Leptospira interrogans from mild and severe leptospirosis patients.

Genomics Inform 2021 Sep 30;19(3):e31. Epub 2021 Sep 30.

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Leptospirosis is a zoonotic disease caused by spirochetes from the genus Leptospira. In Thailand, Leptospira interrogans is a major cause of leptospirosis. Leptospirosis patients present with a wide range of clinical manifestations from asymptomatic, mild infections to severe illness involving organ failure. For better understanding the difference between Leptospira isolates causing mild and severe leptospirosis, illumina sequencing was used to sequence genomic DNA in both serotypes. DNA of Leptospira isolated from two patients, one with mild and another with severe symptoms, were included in this study. The paired-end reads were removed adapters and trimmed with Q30 score using Trimmomatic. Trimmed reads were constructed to contigs and scaffolds using SPAdes. Cross-contamination of scaffolds was evaluated by ContEst16s. Prokka tool for bacterial annotation was used to annotate sequences from both Leptospira isolates. Predicted amino acid sequences from Prokka were searched in EggNOG and David gene ontology database to characterize gene ontology. In addition, Leptospira from mild and severe patients, that passed the criteria e-value < 10e-5 from blastP against virulence factor database, were used to analyze with Venn diagram. From this study, we found 13 and 12 genes that were unique in the isolates from mild and severe patients, respectively. The 12 genes in the severe isolate might be virulence factor genes that affect disease severity. However, these genes should be validated in further study.
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http://dx.doi.org/10.5808/gi.21037DOI Listing
September 2021

Performance of a New Microfluidic Dengue NS1 Immuno-magnetic Agglutination Assay for the Rapid Diagnosis of Dengue Infection in Adults.

Am J Trop Med Hyg 2021 07 19;105(3):771-776. Epub 2021 Jul 19.

5Medical Department, Loei Provincial Hospital, Ministry of Health, Loei, Thailand.

Dengue (DENV) infections are a public health concern worldwide and thus early diagnosis is important to ensure appropriate clinical management. The rapid diagnostic test (RDT) targets nonstructural protein 1 (NS1) detection and is the main tool used for diagnostic purpose. In this study, we evaluated the performance of a new rapid and semi-quantitative microfluidic DENV NS1 immuno-magnetic agglutination assay or IMA (ViroTrack Dengue Acute, BluSense Diagnostics, Copenhagen, Denmark). We studied 233 subjects confirmed to have DENV infection (by a real-time reverse transcriptase polymerase chain reaction) and 200 control samples were taken from patients with confirmed diagnoses of other febrile illnesses, in Thailand. Samples were tested using the NS1 antigen (Ag) detection methods: in-house NS1 Ag ELISA (ELISA), SD BIOLINE Dengue NS1 Ag RDT (ICT), and ViroTrack Dengue Acute (IMA). Sensitivities of these tests were 86.3%, 78.9%, and 85.5%, respectively. All tests showed high specificity (100%, 99%, and 97% for ELISA, ICT, and IMA, respectively). The sensitivities of both RDTs were affected by the low sensitivity to DENV-2 and DENV-4. NS1 Ag was detected in every patient on day 1 and day 2 after onset of illness by ELISA and IMA with a decline in detection rates over time after day 6 of illness. NS1 detection rate using ICT decreased from 100% on day 1 of illness to 98.6% on day 2 after onset of illness. By day 6, the detection rate was 45.9%. Thus, IMA performed better than ICT for early and rapid diagnosis of DENV infections in endemic countries.
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http://dx.doi.org/10.4269/ajtmh.20-1558DOI Listing
July 2021

Epidemiology, clinical characteristics, and treatment outcomes of patients with COVID-19 at Thailand's university-based referral hospital.

BMC Infect Dis 2021 Apr 26;21(1):382. Epub 2021 Apr 26.

Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: The epidemiology and outcomes of COVID-19 patients in Thailand are scarce.

Methods: This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020.

Results: The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive.

Conclusions: The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.
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http://dx.doi.org/10.1186/s12879-021-06081-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072093PMC
April 2021

Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial.

Clin Infect Dis 2021 05;72(10):e586-e593

Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro.

Methods: We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin.

Results: The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9-84.0] hours vs 95.8 [95% CI 83.9-120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups.

Conclusions: A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.
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http://dx.doi.org/10.1093/cid/ciaa1332DOI Listing
May 2021

The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network.

PLoS Med 2020 11 19;17(11):e1003393. Epub 2020 Nov 19.

MARIB-Malaria Research Initiative Bandarban, Vienna, Austria.

Background: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial.

Methods And Findings: A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high.

Conclusions: In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas.
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http://dx.doi.org/10.1371/journal.pmed.1003393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676739PMC
November 2020

Case Report: Recovery of Pathogenic spp. from Routine Aerobic Blood Culture Bottles.

Am J Trop Med Hyg 2020 11;103(5):1834-1837

Department of Medicine, Mahidol University, Bangkok, Thailand.

spp. are fastidious and slow-growing bacteria, making recovery difficult and diagnostic sensitivity in the clinical setting low. However, collection of isolates is valuable for epidemiological and laboratory research. Severe leptospirosis cases may present as septic shock, and the differential diagnosis often includes bacterial septicemia, leading clinicians to collect blood cultures. Here, we report the successful isolation of pathogenic spp. from blood culture bottles (targeting aerobic bacteria incubated at 37°C) from a 64-year-old man admitted with septic shock. The patient presented with 4 days of fever, severe hypotension, transient atrial fibrillation, jaundice, and oliguric renal failure. After admission, intravenous ceftriaxone plus azithromycin was given with fluid resuscitation, norepinephrine infusion, invasive mechanical ventilation, and renal replacement therapy. He was discharged from the hospital 16 days after admission. Using the blood sample obtained on admission, the diagnosis of leptospirosis was confirmed by multiplex real-time PCR (targeting bacterial 16S rRNA and 32 gene). We collected 200 μL from the blood culture bottle to inoculate a 5-mL Ellinghausen, McCullough, Johnson, and Harris media supplemented with 5% fetal bovine serum. After 2 weeks of incubation at 30°C, strains were identified and confirmed by real-time PCR. Genotyping was undertaken using the multi-locus sequence typing (MLST) scheme#1. The isolate matched with ST50 isolates in the PUbMLST database. This case provides evidence that in tropical countries, severe leptospirosis should be considered in patients who present with symptoms of sepsis. Pathogenic may be successfully isolated from aerobic blood cultures in routine clinical settings.
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http://dx.doi.org/10.4269/ajtmh.20-0204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646814PMC
November 2020

Anti-Mycoplasma Activity of Daptomycin and Its Use for Mycoplasma Elimination in Cell Cultures of Rickettsiae.

Antibiotics (Basel) 2019 Aug 21;8(3). Epub 2019 Aug 21.

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

Mycoplasma contamination detrimentally affects cellular functions and the growth of intracellular pathogens in cell cultures. Although several mycoplasmacidal agents are commercially available for sterile cell cultures, they are not applicable to rickettsia-infected cells. In our attempt to find an anti-mycoplasma drug for contaminated rickettsial cultures, we determined the susceptibilities of three common species to daptomycin. and showed low-level resistance to daptomycin (minimum inhibitory concentration, MIC = 2 mg/L), whereas was high-level resistant (MIC = 32 mg/L). However, some isolates developed higher resistance to daptomycin after failed treatments with inadequate doses or durations. An aminoglycoside (gentamicin) was still active against and could be used in cultures. For complete eradication of mycoplasmas in cultures, we recommend a 3-week treatment with daptomycin at 256 mg/L. In contaminated cultures, daptomycin at 32 mg/L was effective in eradicating , whereas either gentamicin or amikacin (100 mg/L) was effective in eradicating . Unlike each drug alone, the combinations of daptomycin plus clindamycin and/or quinupristin/dalfopristin proved effective in eradicating . In summary, our study demonstrated the in vitro anti-mycoplasma activity of daptomycin and its application as a new mycoplasma decontamination method for and cultures.
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http://dx.doi.org/10.3390/antibiotics8030123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784056PMC
August 2019

Clinical outcome and laboratory markers for predicting disease activity in patients with disseminated opportunistic infections associated with anti-interferon-γ autoantibodies.

PLoS One 2019 25;14(4):e0215581. Epub 2019 Apr 25.

Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Clinical courses and treatment outcomes are largely unknown in patients with adult-onset immunodeficiency associated with anti-interferon-gamma autoantibodies due to the fact that it was recently recognized and anti-IFN-γ auto-Abs detection is not widely available.

Methods And Findings: Non-HIV-infected adult patients with detectable anti-IFN-γ auto-Abs diagnosed and followed at Siriraj Hospital, Bangkok, Thailand during January 2013 to November 2016 were prospectively studied. At each follow-up visit, patients were classified as stable or active disease according to symptoms and signs, and all proven OIs were recorded. Laboratory parameters, including erythrocyte sedimentation rate, C-reactive protein, and anti-IFN-γ auto-Abs level, were compared between active and stable disease episodes. We identified 80 patients with this clinical syndrome and followed them up during study period. Seventy-nine patients developed overall 194 proven opportunistic infections. Mycobacterium abscessus (34.5%) and Salmonella spp. (23.2%) were the two most common pathogens identified among these patients. Sixty-three patients were followed for a median of 2.7 years (range 0.6-4.8 years). Eleven (17.5%) patients achieved the drug-free remission period for at least 9 months. Four patients died. Anti-IFN-γ auto-Abs concentration was significantly lower at baseline and decreased over time in the drug-free remission group compared to another group (p = 0.001). C-reactive protein, erythrocyte sedimentation rate and white cell count were found to be useful biomarkers for determining disease activity during follow-up.

Conclusions: Reinfection or relapse of OIs is common despite long-term antimicrobial treatment in patients with anti-IFN-γ auto-Abs. Treatment to modify anti-IFN-γ auto-Abs production may improve long-term outcomes in this patient population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215581PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483193PMC
February 2020

A retrospective molecular study of Cryptosporidium species and genotypes in HIV-infected patients from Thailand.

Parasit Vectors 2019 Mar 12;12(1):91. Epub 2019 Mar 12.

Department of Infectious Disease, Istituto Superiore di Sanità, Rome, Italy.

Background: Opportunistic infections represent a serious health problem for HIV-infected people. Among enteric infections, cryptosporidiosis, a severe and life-threatening diarrheal disease, is of particular importance in low economic settings where access to anti-retroviral therapy is limited. Understanding transmission routes is crucial in establishing preventive measures, and requires the use of informative genotyping methods. In this study, we performed a retrospective analysis of Cryptosporidium species in 166 stool samples collected from 155 HIV-infected patients during 1999-2004 at the Siriraj Hospital in Bangkok, Thailand.

Results: Microscopic examination of stools identified 104 of the 155 patients as positive for Cryptosporidium. Other common pathogens identified were microsporidia, Isospora, Giardia, Strongyloides and Opisthorchis. All samples were tested by amplification of a fragment of the 18S rDNA locus, and sequencing showed the presence of Cryptosporidium hominis (n = 42), C. meleagridis (n = 20), C. canis (n = 12), C. felis (n = 7), C. suis (n = 6) and C. parvum (n = 5). Genotyping at the glycoprotein 60 (gp60) locus revealed substantial variability in isolates of C. hominis and C. meleagridis. Among C. hominis isolates, subtype IeA11G3T3 was the most prevalent, but allelic family Id was the more diverse with four subtypes described, two of which were identified for the first time. Among C. meleagridis isolates, seven subtypes, two of which were new, were found in the allelic family IIIb, along with new subtypes in allelic families IIIe and IIIg. In the four C. parvum isolates, subtype IIoA16G1, a rare subtype previously reported in a Swedish patient who had traveled to Thailand, was identified.

Conclusions: This study confirms the high susceptibility of HIV-infected individuals to infection with different Cryptosporidium species and subtypes, and further stresses the importance of surveillance for opportunistic intestinal protozoans.
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http://dx.doi.org/10.1186/s13071-019-3348-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417249PMC
March 2019

Molecular Evidence of Rickettsia in Human and Dog Blood in Bangkok.

Vector Borne Zoonotic Dis 2018 06 23;18(6):297-302. Epub 2018 Apr 23.

1 Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand .

Rickettsia spp. has been detected in dog fleas in Bangkok, Thailand. With the intent of collecting evidence to confirm the presence of rickettsioses in dogs and to assess the level of associated potential for accidental human infection, human buffy coat from patients with fever of unknown origin (n = 168), whole blood samples from dogs (n = 353), and 19 flea groups from our dog sample population were studied during the 2012 to 2014 study period. The presence of Rickettsia was investigated by molecular detection of 23S rRNA gene of Rickettsia genus, citrate synthase (gltA) gene, and 17-kDa outer membrane gene. All positive samples were confirmed by DNA sequence analysis. Using phylogenetic analysis, three groups of Rickettsia were detected, as follows: Rickettsia felis in 8 patients and 8 dogs; R. felis-like sp. in 2 patients, 5 dogs, and 11 flea samples; and Rickettsia typhi in 3 patients. In addition to confirming the presence of R. felis in Thai patients, the findings of this study suggest that R. felis-like sp. isolated from fleas that were symbiotically coexisting with dogs that we evaluated in this study can transmit and cause disease in dogs and humans in Bangkok.
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http://dx.doi.org/10.1089/vbz.2017.2180DOI Listing
June 2018

Immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination.

Vaccine 2018 01 27;36(2):285-291. Epub 2017 Nov 27.

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Thailand. Electronic address:

Background: Obesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. Moreover, higher volume of passive rabies immunoglobulin (RIG) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. This study aimed to evaluate the effect of obesity on humoral immune responses to combined equine RIG and rabies vaccine treatment among patients with WHO category III exposure to a rabies suspected animal.

Methods: A single centre, prospective, open-labelled study among WHO category III rabies exposed patients was conducted to compare serum rabies virus neutralizing antibody (RVNA) responses measured by rapid fluorescent focus inhibition test between obese (body mass index, BMI > 30 kg/m) and control (BMI < 25 kg/m) patients after combined immunization with equine rabies immunoglobulin and purified chick-embryo cell rabies vaccine for post exposure prophylaxis treatment.

Results: Post-vaccination geometric mean titer (GMT) of RVNA concentrations between two groups at day 7 were 0.33 (95% CI: 0.23, 0.46) vs 0.39 (95% CI: 0.27, 0.55), 4.61 (95% CI: 3.20, 6.63) vs 3.78 (95% CI: 2.77, 5.16) at day 14, and 7.45 (95% CI: 5.86, 9.49) vs 5.93 (95%CI: 4.46-7.90) at day 28 for obese and control patients, respectively. There was no statistically significant difference of RVNA GMT between two groups. Seroconversion to at least adequate concentration (RVNA titer ≥0.5 IU/mL) rates were 34% at day 7 and 100% at days 14 and 28 in both groups. There were no immediate hypersensitivity reaction and no serious adverse events observed during the study period.

Conclusions: There was no evidence of immunosuppression of antibodies' responses in obese patients. Combined ERIG and rabies virus vaccination for post exposure treatment is safe.
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http://dx.doi.org/10.1016/j.vaccine.2017.11.058DOI Listing
January 2018

An ELISA assay using a combination of recombinant proteins from multiple strains of Orientia tsutsugamushi offers an accurate diagnosis for scrub typhus.

BMC Infect Dis 2017 06 10;17(1):413. Epub 2017 Jun 10.

Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD, USA.

Background: Scrub typhus (ST) is a disease caused by an obligate intracellular bacterium, Orientia tsutsugamushi, an organism that requires a BSL3 laboratory for propagation. The disease is hallmarked by an eschar at the site of the chigger bite, followed by the development of fever, malaise, myalgia, anorexia, and papulomacular rash. Indirect immunofluorescent assay (IFA) is the gold standard for scrub typhus diagnosis, however, the subjectivity of the assay, the need for a specialized laboratory and instruments has limited the wide use of the test in resource limited areas.

Methods: A recombinant-protein based enzyme linked immunosorbent assay (ELISA) using the most abundant and immunodominant protein for the detection of Orientia specific antibodies in serum has been developed. The performance of the assay was evaluated using prospectively collected acute sera from 248 randomly selected patients in Thailand. The ELISA assay was evaluated using two different cutoff values.

Results: The receiver operating characteristic (ROC) curve generated cutoff values gave slightly better consistency with diagnosis of ST than those cutoff values established by averaging ELISA optical density of known negatives at 99% confidence interval. Both cutoff values provided similar statistical parameters when compared with the diagnosis of ST, indicating the validity of both calculations to derive cutoff values. These results suggest that both IgG and IgM ELISA performed well to accurately diagnose scrub typhus cases in endemic areas using only acute serum samples.

Conclusions: We have successfully developed an ELISA assay for the detection of Orientia-specific antibodies in serum that could provide effective screening of acute sera under clinical setup and it is also a useful assay to estimate seroprevalence in various endemic areas.
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http://dx.doi.org/10.1186/s12879-017-2512-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466769PMC
June 2017

Comparative evaluation of 2 rapid immunochromatographic assays for Orientia tsutsugamushi in northeastern Thailand.

Diagn Microbiol Infect Dis 2017 07 3;88(3):290-291. Epub 2017 May 3.

Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD, USA; Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

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http://dx.doi.org/10.1016/j.diagmicrobio.2017.04.010DOI Listing
July 2017

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection.

PLoS One 2017 24;12(4):e0176342. Epub 2017 Apr 24.

Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: The clinical syndrome of disseminated nontuberculous mycobacterial (NTM) infection in patients who were previously healthy is now well recognized to be associated with an acquired autoantibody to Interferon gamma (Anti IFN- γ autoantibody). However, the risk factors of this syndrome remain unknown.

Method: We performed an unmatched case control study among patients with NTM diseases who were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method. Cases were patients with NTM diseases and detectable anti IFN- γ autoantibody. Controls were randomly selected from those with undetectable anti IFN- γ autoantibody. Data from both groups including demographic data, clinical presentation, laboratory results, other risk factors and HLA genotypes were collected. Univariate and multivariate analyses were performed to identify independent risk factors for this syndrome.

Results: 70 cases (mean age 50 ± 11 years) and 70 controls (mean age 58 ± 18 years) were enrolled into the study. Mycobacterial abscessus was the most common NTM pathogen found in both groups (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM disease was significantly more common in cases (92.9%) than in the controls (14.3%, p<0.001). Binary logistic regression analysis showed that previous OIs (adjusted OR14.87, 95% CI 2.36-93.86), birthplace outside Central region (adjusted OR 19.19, 95% CI 3.86-95.35), lack of comorbidities lead to immunosuppression, such as HIV infection or diabetes mellitus (adjusted OR 23.68, 95% CI 4.01-139.94), and presence of HLA DRB1*15/16 (adjusted OR 153.28, 95% CI 16.87-139.88) were independent factors associated with this syndrome.

Conclusion: Patients with NTM disease associated with anti IFN- γ autoantibody are almost always previously healthy and HIV negative. Most of these patients presented with disseminated NTM disease with generalized lymphadenitis and often with reactive skin lesions. Factors associated with detectable anti IFN- γ autoantibody are HLA-DRB1 and DQB1 alleles, and history of previous OIs in patients without comorbidity that leads to immunosuppression. Further studies are needed to better understand these associations and to improve the treatment outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402934PMC
September 2017

Use of Multiplex Real-Time PCR To Diagnose Scrub Typhus.

J Clin Microbiol 2017 05 15;55(5):1377-1387. Epub 2017 Feb 15.

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

Scrub typhus, caused by , is a common cause of acute undifferentiated febrile illness in the Asia-Pacific region. However, its nonspecific clinical manifestation often prevents early diagnosis. We propose the use of PCR and serologic tests as diagnostic tools. Here, we developed a multiplex real-time PCR assay using hydrolysis (TaqMan) probes targeting 47-kDa, , and human interferon beta (IFN-β gene) genes to improve early diagnosis of scrub typhus. The amplification efficiency was higher than 94%, and the lower detection limit was 10 copies per reaction. We used a human gene as an internal DNA quality and quantity control. To determine the sensitivity of this PCR assay, we selected patients with confirmed scrub typhus who exhibited a clear 4-fold increase in the level of IgG and/or IgM. The PCR assay result was positive in 45 of 52 patients, indicating a sensitivity of 86.5% (95% confidence interval [CI]: 74.2 to 94.4). The PCR assessment was negative for all 136 non-scrub typhus patients, indicating a specificity of 100% (95% CI: 97.3 to 100). In addition, this test helped diagnose patients with inconclusive immunofluorescence assay (IFA) results and using single blood samples. In conclusion, the real-time PCR assay proposed here is sensitive and specific in diagnosing scrub typhus. Combining PCR and serologic tests will improve the diagnosis of scrub typhus among patients presenting with acute febrile illness.
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http://dx.doi.org/10.1128/JCM.02181-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405255PMC
May 2017

Scrub Typhus in Northeastern Thailand: Eschar Distribution, Abnormal Electrocardiographic Findings, and Predictors of Fatal Outcome.

Am J Trop Med Hyg 2016 10 29;95(4):769-773. Epub 2016 Aug 29.

Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Scrub typhus is endemic in Thailand. Of the 495 patients with acute undifferentiated fever studied in Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand, from June 1, 2011, to December 31, 2012, 146 patients (29.5%) had confirmed scrub typhus. The majority of cases were male, farmers, with the mean (±standard deviation) age of 54.1 ± 15.2 years. A total of 59 patients (40.4%) had eschar lesion. The commonest sites for an eschar in male patients were the perineum, inguinal, and buttock area; whereas in females, it was the head and neck area. Abnormal electrocardiogram was found in 39 of 79 patients (49.4%) with sinus tachycardia being the most frequent finding (17, 21.5%). A total of 73 patients (50%) had at least one complication. Myocarditis was the cause of complete heart block in a scrub typhus patient, and he fully recovered after receiving intravenous chloramphenicol treatment. The case fatality rate was 6.2% (nine deaths).The independent predictors for fatal outcome were age over 65 years (odds ratio [OR] = 14.49, 95% confidence interval [CI] = 1.26-166.44, P = 0.03), acute kidney injury (OR = 12.75, 95% CI = 1.77-92.07, P = 0.01), and hyperbilirubinemia (OR = 24.82, 95% CI = 2.12-286.61, P = 0.01). Early diagnosis and prompt appropriate treatment can improve the patient's outcome.
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http://dx.doi.org/10.4269/ajtmh.16-0088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062771PMC
October 2016

Immunological evidence of Zika virus transmission in Thailand.

Asian Pac J Trop Med 2016 Feb 13;9(2):141-4. Epub 2016 Jan 13.

Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Objective: To identify immunological evidence of Zika virus transmission in Thailand.

Methods: To undertake a preliminary serosurvey of possible exposure to Zika virus, 21 serum samples from cohort of acute undifferentiated fever patients were examined for immunoreactivity to Zika, Dengue, Japanese encephalitis and Chikungunya envelope antigens by Western blot analysis.

Results: Twenty of the 21 serum samples showed immunoreactivity to at least one of the antigens, with seven samples showing immunoreactivity to all antigens. Of particular note, two serum samples showed immunoreactivity only to Zika envelope antigen, with no immunoreactivity to other envelope antigens.

Conclusions: This study presents the first evidence of Zika virus transmission in Thailand, although as yet the relationship between transmission and possible cases of Zika fever in Thailand requires further investigation.
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http://dx.doi.org/10.1016/j.apjtm.2016.01.017DOI Listing
February 2016

Highly Sensitive Loop-Mediated Isothermal Amplification for the Detection of Leptospira.

Int J Bacteriol 2015 27;2015:147173. Epub 2015 Jan 27.

Naval Medical Research Center, Silver Spring, MD 20910, USA; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Leptospirosis is a worldwide zoonosis caused by an infection with the pathogenic species of Leptospira. We have developed a loop-mediated isothermal amplification (LAMP) assay to detect the DNA of Leptospira spp. Six sets of primers targeting the gene of the subsurface protein, lipL32, were evaluated for their detection sensitivity. The best primer set detected less than 25 copies of lipL32 per reaction of both plasmid DNA template and purified leptospiral genomic DNA. By combining primers targeting lipL32 with the previously published primer set targeting lipL41, the sensitivity of the assay was improved to 12 copies of L. interrogans. The specificity of the LAMP assay was evaluated by using the genomic DNA from other clinically encountered bacterial species such as different strains of Orientia tsutsugamushi, Rickettsia typhi, Rickettsia conorii, Rickettsia rickettsii, Coxiella burnetii, and Bartonella bacilliformis. These genomic DNA samples were all negative in our LAMP assay. The sensitivity of the LAMP assay was very similar to that of quantitative real time PCR. Several detection methods for the amplified product of LAMP assay were performed to demonstrate the simplicity of the assay. In summary, our results have suggested that this assay is rapid, robust, and easy to perform and has the potential to be used in endemic locations.
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http://dx.doi.org/10.1155/2015/147173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745460PMC
February 2016

Anti-IFN-γ autoantibodies are strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia.

J Allergy Clin Immunol 2016 Mar 29;137(3):945-8.e8. Epub 2015 Oct 29.

Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

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http://dx.doi.org/10.1016/j.jaci.2015.09.018DOI Listing
March 2016

Serological diagnosis of pulmonary Mycobacterium tuberculosis infection by LIPS using a multiple antigen mixture.

BMC Microbiol 2015 Oct 8;15:205. Epub 2015 Oct 8.

Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.

Background: There is an urgent need for a simple and accurate test for the diagnosis of human Mycobacterium tuberculosis, the infectious agent causing tuberculosis (TB). Here we describe a serological test based on light emitting recombinant proteins for the diagnosis of pulmonary Mycobacterium tuberculosis infection.

Methods: Luciferase Immunoprecipitation Systems (LIPS), a fluid-phase immunoassay, was used to examine antibody responses against a panel of 24 different M. tuberculosis proteins. Three different strategies were used for generating the constructs expressing the recombinant fusion M. tuberculosis proteins with luciferase: synthetic gene synthesis, Gateway recombination cloning, and custom PCR synthesis. A pilot cohort of African pulmonary TB patients was used for initial antibody screening and confirmatory studies with selected antigens were performed with a cohort from Thailand and healthy US blood donors. In addition to testing M. tuberculosis antigens separately, a mixture that tested seven antigens simultaneously was evaluated for diagnostic performance.

Results: LIPS testing of a pilot set of serum samples from African pulmonary TB patients identified a potential subset of diagnostically useful M. tuberculosis antigens. Evaluation of a second independent cohort from Thailand validated highly significant antibody responses against seven antigens (PstS1, Rv0831c, FbpA, EspB, bfrB, HspX and ssb), which often showed robust antibody levels up to 50- to 1000-fold higher than local community controls. Marked heterogeneity of antibody responses was observed in the patients and the combined results demonstrated 73.5% sensitivity and 100% specificity for detection of pulmonary TB. A LIPS test simultaneously employing the seven M. tuberculosis antigen as a mixture matched the combined diagnostic performance of the separate tests, but showed an even higher diagnostic sensitivity (90%) when a cut-off based on healthy US blood donors was used.

Conclusion: A LIPS immunoassay employing multiple M. tuberculosis antigens shows promise for the rapid and quantitative serological detection of pulmonary TB.
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http://dx.doi.org/10.1186/s12866-015-0545-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599810PMC
October 2015

Retrospective screening of acute undifferentiated fever serum samples with universal flavivirus primers.

J Infect Dev Ctries 2015 Jul 30;9(7):760-4. Epub 2015 Jul 30.

Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Introduction: Fever is a common symptom of many tropical diseases and in many cases the etiologic agent remains unidentified as a consequence of either the etiologic agent not being part of routine diagnostic screening or as a consequence of false negatives on standard diagnostic tests.

Methodology: This study screened a well characterized panel of 274 serum samples collected on day of admission from adult patients with acute undifferentiated fever admitted to a hospital in Nakhon Ratchasima, Thailand by RT-PCR using pan-flavivirus degenerate primers.

Results: Subsequent clinical diagnosis was achieved for 38 of the patients, and included 19 cases of dengue fever. RT-PCR screening identified seven positive samples (2.5%) which were revealed by sequence analysis to be dengue virus 1 (2 cases), dengue virus 2 (2 cases) and dengue virus 3 (3 cases). Only 5 out of 19 (26%) serum samples from patients subsequently diagnosed with dengue were positive, but 2 samples which clinically remained undiagnosed were shown to be positive for dengue virus. Sequence analysis suggested that the dengue virus 3 cases occurred as a result of importation of a strain of dengue from India or China. No other flaviviruses were identified.

Conclusions: No evidence was found of other flaviviruses besides dengue circulating in this population. Despite improved diagnostic tests, cases of dengue are still evading correct diagnosis.
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http://dx.doi.org/10.3855/jidc.5866DOI Listing
July 2015

HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies.

PLoS One 2015 26;10(5):e0128481. Epub 2015 May 26.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Recently a newly identified clinical syndrome of disseminated non-tuberculous mycobacterial diseases (with or without other opportunistic infections in adult patients who were previously healthy, has been recognized in association with an acquired autoantibody to interferon-gamma. This syndrome is emerging as an important cause of morbidity and mortality, especially among people of Asian descent. Trigger for the production of this autoantibody remains unknown, but genetic factors are strongly suspected to be involved. We compared HLA genotyping between 32 patients with this clinical syndrome, and 38 controls. We found that this clinical syndrome was associated with very limited allele polymorphism, with HLA-DRB1 and DQB1 alleles, especially HLA-DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02. Odds ratio of DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02 were 7.03 (95% CI, 2.18-22.69, P<0.0001, 9.06 (95% CI, 2.79-29.46, P<0.0001), 6.68 (95% CI, 2.29-19.52, P = 0.0004), and 6.64 (95% CI, 2.30-19.20, P = 0.0004), respectively. Further investigation is warranted to provide better understanding on pathogenesis of this association.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128481PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444022PMC
April 2016

Orientia tsutsugamushi, agent of scrub typhus, displays a single metapopulation with maintenance of ancestral haplotypes throughout continental South East Asia.

Infect Genet Evol 2015 Apr 8;31:1-8. Epub 2015 Jan 8.

UM2, CPBS, UMR 5236, CNRS-UM1-UM2, 1919 route de Mende, 34293 Montpellier Cedex 5, France; Cirad, UMR 17, Cirad-Ird, TA-A17/G, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France. Electronic address:

Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness in rural area of Asia-Pacific region. A multi-locus sequence typing (MLST) analysis was performed on strains isolated from human patients from 3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of the 56-kDa protein encoding gene was analyzed on the same strains and showed a structured topology with genetically distinct clusters. MLST analysis did not lead to the same conclusion. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity whereas the ST distribution indicated the presence of isolated patches. No correlation was found with the geographic origin. This work suggests that weak divergence in core genome and ancestral haplotypes are maintained by permanent recombination in mites while the 56-kDa protein gene is diverging in higher speed due to selection by the mammalian immune system.
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http://dx.doi.org/10.1016/j.meegid.2015.01.005DOI Listing
April 2015

Human leptospirosis trends: northeast Thailand, 2001-2012.

Int J Environ Res Public Health 2014 Aug 20;11(8):8542-51. Epub 2014 Aug 20.

Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

The objective of this study was to determine the changing trend of leptospirosis over time in Thailand using two prospective hospital-based studies conducted amongst adult patients with acute undifferentiated fever (AUFI) admitted to Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand between July 2001 to December 2002 and between July 2011 to December 2012. During the first period, leptospirosis (98 patients, 40%) and scrub typhus (59 patients, 24.1%) were the two major causes of AUFI. In the second period, scrub typhus (137 patients, 28.3%) was found to be more common than leptospirosis (61 patients, 12.7%). Amongst patients with leptospirosis, the proportion of male patients and the median age were similar. Leptospira interrogans serogroup Autumnalis was the major infecting serogroup in both study periods. The case fatality rate of leptospirosis was significantly higher in 2011-2012 as compared with the case fatality rate in 2001-2002 (19.7% vs. 6.3%, p < 0.001). In summary, we found that number of leptospirosis cases had decreased over time. This trend is similar to reportable data for leptospirosis complied from passive surveillance by the Ministry of Public Health, Thailand. However, the case fatality rate of severe leptospirosis has increased. Severe lung hemorrhage associated with leptospirosis remained the major cause of death.
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http://dx.doi.org/10.3390/ijerph110808542DOI Listing
August 2014

Epidemiology of leptospira transmitted by rodents in southeast Asia.

PLoS Negl Trop Dis 2014 Jun 5;8(6):e2902. Epub 2014 Jun 5.

Institut des Sciences de l'Evolution, CNRS-IRD-UM2, Université de Montpellier 2, Montpellier, France; CIRAD, UR AGIRs, Montpellier, France; Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Ratchathevi, Thailand.

Background: Leptospirosis is the most common bacterial zoonoses and has been identified as an important emerging global public health problem in Southeast Asia. Rodents are important reservoirs for human leptospirosis, but epidemiological data is lacking.

Methodology/principal Findings: We sampled rodents living in different habitats from seven localities distributed across Southeast Asia (Thailand, Lao PDR and Cambodia), between 2009 to 2010. Human isolates were also obtained from localities close to where rodents were sampled. The prevalence of Leptospira infection was assessed by real-time PCR using DNA extracted from rodent kidneys, targeting the lipL32 gene. Sequencing rrs and secY genes, and Multi Locus Variable-number Tandem Repeat (VNTR) analyses were performed on DNA extracted from rat kidneys for Leptospira isolates molecular typing. Four species were detected in rodents, L. borgpetersenii (56% of positive samples), L. interrogans (36%), L. kirschneri (3%) and L. weilli (2%), which were identical to human isolates. Mean prevalence in rodents was approximately 7%, and largely varied across localities and habitats, but not between rodent species. The two most abundant Leptospira species displayed different habitat requirements: L. interrogans was linked to humid habitats (rice fields and forests) while L. borgpetersenii was abundant in both humid and dry habitats (non-floodable lands).

Conclusion/significance: L. interrogans and L. borgpetersenii species are widely distributed amongst rodent populations, and strain typing confirmed rodents as reservoirs for human leptospirosis. Differences in habitat requirements for L. interrogans and L. borgpetersenii supported differential transmission modes. In Southeast Asia, human infection risk is not only restricted to activities taking place in wetlands and rice fields as is commonly accepted, but should also include tasks such as forestry work, as well as the hunting and preparation of rodents for consumption, which deserve more attention in future epidemiological studies.
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http://dx.doi.org/10.1371/journal.pntd.0002902DOI Listing
June 2014

Nine human sparganosis cases in Thailand with molecular identification of causative parasite species.

Am J Trop Med Hyg 2014 Aug 19;91(2):389-93. Epub 2014 May 19.

Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

Human sparganosis is one of the neglected diseases but important food-borne parasitic zoonoses. The disease is caused by larvae (spargana) of diphyllobothriidean tapeworm. Here, we describe nine cases of human sparganosis, caused by Spirometra erinaceieuropaei in a hospital in Thailand during 2001-2012. Clinical characteristics, treatment, and outcome of cases were revealed. Diagnosis and identification of causative parasite species was made by histopathological investigations followed by a polymerase chain reaction-based molecular method using formalin-fixed paraffin embedded tissues. The DNA samples were extracted from tissues and a partial fragment of cytochrome c oxidase subunit 1 (cox1) gene was amplified for the detection of parasitic DNA. Infection could be prevented by increasing activities on health communication by responsible public health agencies.
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http://dx.doi.org/10.4269/ajtmh.14-0178DOI Listing
August 2014

Prevalence and risk factors of acquiring Strongyloides stercoralis infection among patients attending a tertiary hospital in Thailand.

Pathog Glob Health 2014 Apr;108(3):137-40

Objectives: We aimed to determine the prevalence and risk factors for Strongyloides stercoralis infection in adult patients attending Siriraj Hospital, a tertiary hospital in Thailand.

Methods: A case-control study was carried out between July 2008 and April 2010. Case and control were identified from 6022 patients for whom results of faecal examination were available. A case was a patient who had S. stercoralis larva detected from faecal examination. Control was randomly selected from patients without S. stercoralis larvae detected in three consecutive faecal examinations. The proportion of control to case was 2 : 1. Demographic and clinical data for the day of diagnosis and retrospectively up to 15 days preceding the date of faecal examination were reviewed from their medical records.

Results: Overall, 149 (2.47%) patients had S. stercoralis larvae positive. There were 105 males (70.5%), with the mean (SD) age of 53.9 (17.2) years. A total of 300 controls were selected. Male gender (odds ratio (OR)  =  2.79, 95% confidence interval (CI) 1.78-4.27)), human immunodeficiency virus (HIV) infection (OR  =  3.23, 95% CI 1.43-7.29), and eosinophilia (OR  =  1.81, 95% CI 1.33-2.47) were found to be independent risk factors associated with S. stercoralis infection in this setting. Corticosteroid or other immunosuppressive treatment, and other concomitant illnesses were not associated with increased risk of S. stercoralis infection.

Conclusion: In this setting, strongyloidiasis was seen more often in male patients with eosinophilia and with HIV infection. Prevention of fatal complication caused by S. stercoralis by regular faecal examination, or serology for early detection and treatment of undiagnosed S. stercoralis infection, is warranted in these high-risk patients.
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http://dx.doi.org/10.1179/2047773214Y.0000000134DOI Listing
April 2014

Infectious diseases and their outbreaks in Asia-Pacific: biodiversity and its regulation loss matter.

PLoS One 2014 25;9(2):e90032. Epub 2014 Feb 25.

Department of Civil and Environmental Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.

Despite increasing control measures, numerous parasitic and infectious diseases are emerging, re-emerging or causing recurrent outbreaks particularly in Asia and the Pacific region, a hot spot of both infectious disease emergence and biodiversity at risk. We investigate how biodiversity affects the distribution of infectious diseases and their outbreaks in this region, taking into account socio-economics (population size, GDP, public health expenditure), geography (latitude and nation size), climate (precipitation, temperature) and biodiversity (bird and mammal species richness, forest cover, mammal and bird species at threat). We show, among countries, that the overall richness of infectious diseases is positively correlated with the richness of birds and mammals, but the number of zoonotic disease outbreaks is positively correlated with the number of threatened mammal and bird species and the number of vector-borne disease outbreaks is negatively correlated with forest cover. These results suggest that, among countries, biodiversity is a source of pathogens, but also that the loss of biodiversity or its regulation, as measured by forest cover or threatened species, seems to be associated with an increase in zoonotic and vector-borne disease outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090032PLOS
October 2014

Prognostic indicators in adults hospitalized with falciparum malaria in Western Thailand.

Malar J 2013 Jul 8;12:229. Epub 2013 Jul 8.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Background: Severe malaria remains a major cause of death and morbidity amongst adults in the Asiatic tropics.

Methods: A retrospective analysis of the clinical and laboratory data of 988 adult patients, hospitalized with Plasmodium falciparum malaria and prospectively recruited to malaria studies in western Thailand between 1986 and 2002, was performed to assess the factors associated with a fatal outcome. Different severity scores and classifications for defining severe malaria were compared and, using multiple logistic regression, simple models for predicting mortality developed.

Results: The proportion of patients fulfilling the WHO 2000 definition of severe malaria was 78.1%, and their mortality was 10%. Mortality in patients given parenteral artesunate or artemether (16/317, 5%) was lower than in those given parenteral quinine (59/442, 13%) (P < 0.001). Models using parameter sets based on WHO 1990, 2000 and Adapted AQ criteria plus blood smear parasite-stage assessment gave the best mortality prediction. A malaria prognostic index (MPI), derived from the dataset using five clinical or laboratory variables gave similar prognostic accuracy.

Conclusions: The mortality of severe malaria in adults has fallen and the switch from quinine to artesunate has probably been an important contributor. Prognostic indices based on WHO 2000 definitions, and other simpler indices based on fewer variables, provide clinically useful predictions of outcome in Asian adults with severe malaria.
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http://dx.doi.org/10.1186/1475-2875-12-229DOI Listing
July 2013

Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.

J Immunol 2013 Apr 18;190(8):3959-66. Epub 2013 Mar 18.

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Cryptococcal meningitis has been described in immunocompromised patients, as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryptococcal control. We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in four current patients with cryptococcal meningitis and identified and tested 103 archived plasma/cerebrospinal fluid samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody-containing plasmas to inhibit GM-CSF signaling. We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis (PAP). Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the seven later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal PBMCs. This effect was limited to their IgG fraction. Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated PAP.
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http://dx.doi.org/10.4049/jimmunol.1202526DOI Listing
April 2013
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