SummaryBackgroundSince the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.MethodsThis randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.Findings313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the pr...

of 200 words)In the age of a pandemic, such as the ongoing one caused by SARS-CoV-2, the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to This article is protected by copyright. All rights reserved. Accepted Articleevaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time PCR, were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct>35), 2 out of 15 pools (13.3%) were false negative. Pooling specimens to test for COVID-19 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower risk populations.

Immune defects in interleukin-12-dependent interferon-gamma (IFN-γ) pathways are associated with disseminated infections caused by non-tuberculous mycobacteria (NTM) and Salmonella. Recently, there have been an increasing number of reports of acquired autoantibodies to IFN-γ in adults, especially in Asian patients. We describe here three human immunodeficiency virus-negative Thai adults who had persistent or recurrent disseminated infections caused by NTM, Salmonella, and other opportunistic pathogens, possibly due to anti-IFN-γ autoantibodies. The antibodies were shown to exhibit very high inhibitory activity to IFN-γ. Two patients also developed Sweet's syndrome during the course of infections. In addition, we also review all previous reports of patients with anti-IFN-γ antibodies who were susceptible to NTM and Salmonella infections.

Summary Background Influenza continues to have a significant socioeconomic and health impact despite a long established vaccine program and approved antivirals. Preclinical data suggest combination antivirals might be more effective than oseltamivir alone in the treatment of influenza. Methods We conducted a randomized, double-blinded, multicenter phase 2 trial of combination antivirals versus monotherapy for the treatment of influenza. Participants ≥18 years with influenza at increased risk of complications from influenza were randomized by an online computer-generated randomization system to receive either oseltamivir, amantadine, and ribavirin or oseltamivir alone for 5 days, and followed for 28 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at Day 3. Among the secondary outcomes, there were safety and time to alleviation of influenza clinical symptoms. ClinicalTrials.gov Identifier: NCT01227967. Findings Between March 2011 and April 2016 we randomized 633 participants. Seven participants were excluded from analysis: 3 were given treatment without randomization, 3 withdrew before taking any medication, and 1 was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 of 200 (40.0%) participants in the combination arm had virus detectable at Day 3 compared to 97 of 194 (50.0%) (95%C.I. 0.2–19.8%, p=0.046) in the control arm. There was no benefit, however, in multiple clinical secondary endpoints, such as median duration of symptoms (4.5 days in the combination arm vs 4.0 days in the oseltamivir arm; p = 0.21). Interpretation Although oseltamivir, amantadine, and ribavirin showed a statistically significant decrease in viral shedding at Day 3 relative to oseltamivir, this difference was not associated with improved clinical benefit. More work is needed to understand the lack of clinical benefit when a difference in virologic outcome was identified. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States.

Abstract. We report a case of visceral leishmaniasis in a human immunodeficiency virus (HIV)-infected 37-year-old Thai fisherman who presented with nephritonephrotic syndrome, fever, anemia, and thrombocytopenia. Bone marrow biopsy revealed many amastigotes within macrophages. Kidney biopsy showed membranoproliferative glomerulonephritis. Polymerase chain reaction (PCR) and nucleotide sequence analysis of the internal transcribed spacer 1 of the small subunit ribosomal RNA gene in blood and kidney biopsy specimens showed Leishmania species previously described in a Thai patient with visceral leishmaniasis. Only four autochthonous cases of leishmaniasis have been reported in Thailand since 1996. To the best of our knowledge, this is the first report of autochthonous visceral leishmaniasis in an HIV-infected Thai. With an increasing number of patients with autochthonous leishmaniasis in association with the presence of potential vector, it remains to be determined whether this vector-borne disease will become an emerging infectious disease in Thailand.Leishmaniasis is a vector-borne infection caused by an obligate intracellular protozoon, Leishmania sp., which is transmitted by phlebotomine sandflies.1-3 It occurs worldwide in tropical and subtropical regions including the Middle East, India, China, Africa, and southern and central America. Thailand is not a known endemic area for leishmaniasis. Most imported cases were reported between 1960 and 1986 in Thai workers returning from the Middle East. 4,5 The first reported indigenous patient with leishmaniasis was a 3-year-old girl living at Suratthani Province of southern Thailand in 1996.6 Several autochthonous cases with leishmaniasis were recently seen in northern, central, and southern Thailand.7-9 Interestingly, these patients were from provinces where a potential sandfly vector has never been reported. [10][11][12] We describe the first report of visceral leishmaniasis in a human immunodeficiency virus (HIV)-infected patient and review all previous reports of autochthonous cases of leishmaniasis in Thailand. CASE REPORTA 37-year-old Thai fisherman with known HIV infection presented with progressive leg edema, ascites, and low-grade fever of 8 weeks duration. Seven weeks prior to admission (PTA), he was hospitalized at Chantaburi Provincial Hospital with a diagnosis of nephritonephrotic syndrome (hypertension, edema, heavy proteinuria, microscopic hematuria, azotemia, hypoalbuminemia, and hypercholesterolemia). He was treated with prednisolone 50 mg/day. Two weeks PTA, he had not improved and developed thrombocytopenia (platelet count of 85,000/µL) and anemia (hematocrit decreased from 29% to 23.4%). Bone marrow aspiration and biopsy were performed and revealed decreased cellularity and many "yeast-like" organisms 1-2 µM in size. Fungal cultures of both specimens did not grow any fungi. He was then transferred to King Chulalonkorn Memorial Hospital in Bangkok for further evaluation. The patient was born at Chantaburi, eastern Thailand. He had never been outside...

No abstract

This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients.

Purpose: The emergence of isoniazid-resistant tuberculosis (HR-TB) is a global public health problem, causing treatment failure and high mortality rates. This study aimed to determine the minimal inhibitory concentration (MIC) of isoniazid and detect the gene mutation in HR-TB and any association between the level of isoniazid resistance and gene mutation. Methods: We collected 74 clinical HR-TB isolates from two tertiary-care centers in Thailand. MICs were established using broth macrodilution. A line probe assay (LPA) was used to detect gene mutations that confer resistance to isoniazid, rifampicin, aminoglycosides, and fluoroquinolones. Results: Sixty-one (82.4%) isolates were monoresistant to isoniazid and 44 (72.1%) were highly resistant to isoniazid. From the clinical isolates, the range of isoniazid MICs was 0.4-16 μg/mL. The katG S315T gene mutation was the prominent mutation in both isoniazid-monoresistant TB (70.5%) and multidrug-resistant TB (72.7%) isolates. The positive predictive value (PPV) of katG was 100% in detecting high levels of isoniazid resistance. The PPV of the inhA mutation was 93.8% in detecting low levels of isoniazid resistance. Five isolates (6.8%) exhibited low-level phenotypic resistance, whereas an LPA failed to detect an isoniazid gene mutation. Our study found one HR-TB isolate with a gyrA fluoroquinoloneresistant gene mutation. Conclusion: Most HR-TB isolates had high isoniazid-resistance levels associated with the katG gene mutation. High-dose isoniazid should be used with caution in patients with HR-TB. Early detection of drug resistance by genotypic assay can help determine an appropriate regimen.