Pharmacometrics of high dose ivermectin in early COVID-19: an open label, randomized, controlled adaptive platform trial (PLATCOV)

Background: There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infections. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has clinically significant antiviral activity in vivo is uncertain. Methods: In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high-dose oral ivermectin (600 µg/kg daily for 7 days), the monoclonal antibodies casirivimab and imdevimab (600 mg/600 mg), and no study drug. The primary outcome was the comparison of viral clearance rates in the modified intention-to-treat population. This was derived from daily log10 viral densities in standardized duplicate oropharyngeal swab eluates. This ongoing trial is registered at https://clinicaltrials.gov/ (NCT05041907). Results: Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Following ivermectin, the mean estimated rate of SARS-CoV-2 viral clearance was 9.1% slower (95% confidence interval [CI] –27.2% to +11.8%; n=45) than in the no drug arm (n=41), whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster (95% CI +7.0% to +115.1%; n=10 (Delta variant) vs. n=41). Conclusions: High-dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Pharmacometric evaluation of viral clearance rate from frequent serial oropharyngeal qPCR viral density estimates is a highly efficient and well-tolerated method of assessing SARS-CoV-2 antiviral therapeutics in vitro

False Positivity of Anti-SARS-CoV-2 Antibodies in Patients with Acute Tropical Diseases in Thailand

Serology remains a useful indirect method of diagnosing tropical diseases, especially in dengue infection. However, the current literature regarding cross-reactivity between SARS-CoV-2 and dengue serology is limited and revealed conflicting results. As a means to uncover relevant serological insight involving antibody classes against SARS-CoV-2 and cross-reactivity, anti-SARS-CoV-2 IgA, IgM, and IgG ELISA, based on spike and nucleocapsid proteins, were selected for a fever-presenting tropical disease patient investigation. The study was conducted at the Faculty of Tropical Medicine during March to December 2021. The study data source comprised (i) 170 non-COVID-19 sera from 140 adults and children presenting with acute undifferentiated febrile illness and 30 healthy volunteers, and (ii) 31 COVID-19 sera from 17 RT-PCR-confirmed COVID-19 patients. Among 170 non-COVID-19 samples, 27 were false positives (15.9%), of which IgA, IgM, and IgG cross-reactive antibody classes were detected in 18 (10.6%), 9 (5.3%), and 3 (1.8%) cases, respectively. Interestingly, one case exhibited both IgA and IgM false positivity, while two cases exhibited both IgA and IgG false positivity. The false positivity rate in anti-SARS-CoV-2 IgA and IgM was reported in adults with dengue infection (11.3% and 5%) and adults with other tropical diseases (16.7% and 13.3%). The urea dissociation method applied to mitigate false positivity resulted in significantly decreased ELISA-based false and true positives. In conclusion, the analysis of antibody against SARS-CoV-2 in sera of patients with different tropical diseases showed that high IgA and IgM false positivity thus potentially limits serological assay utility in fever-presenting patients in tropical areas

Effect of homologous or heterologous vaccine booster over two initial doses of inactivated COVID-19 vaccine

ABSTRACTIntroduction Inactivated vaccines were delivered to low- and middle-income countries during the early pandemics of COVID-19. Currently, more than 10 inactivated COVID-19 vaccines have been developed. Most inactivated vaccines contain an inactivated whole-cell index SARS-CoV-2 strain that is adjuvant. Whole virions inactivated with aluminum hydroxide vaccines were among the most commonly used. However, with the emerging of COVID-19 variants and waning of the immunity of two doses of after 3 months, WHO and many local governments have recommended the booster-dose program especially with heterologous platform vaccine.Area Covered This review was conducted through a literature search of the MEDLINE database to identify articles published from 2020 to 2023 covered the inactivated COVID-19 vaccines primary series with homologous and heterologous booster focusing on safety, immunogenicity, efficacy, and effectiveness.Expert opinion The inactivated vaccines, especially whole virion inactivated in aluminum hydroxide appeared to be safe and had good priming effects. Immune responses generated after one dose of heterologous boost were high and able to preventing severity of disease and symptomatic infection. A new approach to inactivated vaccine has been developed using inactivating recombinant vector virus-NDV-HXP-S vaccine

<i>Strongyloides stercoralis</i>: A Neglected but Fatal Parasite

Strongyloidiasis is a disease caused by Strongyloides stercoralis and remains a neglected tropical infection despite significant public health concerns. Challenges in the management of strongyloidiasis arise from wide ranging clinical presentations, lack of practical high sensitivity diagnostic tests, and a fatal outcome in immunocompromised hosts. Migration, globalization, and increased administration of immunomodulators, particularly during the COVID-19 era, have amplified the global impact of strongyloidiasis. Here, we comprehensively review the diagnostic tests, clinical manifestations, and treatment of strongyloidiasis. The review additionally focuses on complicated strongyloidiasis in immunocompromised patients and critical screening strategies. Diagnosis of strongyloidiasis is challenging because of non-specific presentations and low parasite load. In contrast, treatment is simple: administration of single dosage ivermectin or moxidectin, a recent anthelmintic drug. Undiagnosed infections result in hyperinfection syndrome and disseminated disease when patients become immunocompromised. Thus, disease manifestation awareness among clinicians is crucial. Furthermore, active surveillance and advanced diagnostic tests are essential for fundamental management

Antimicrobial Stewardship in Tropical Infectious Diseases: Focusing on Dengue and Malaria

Acute undifferentiated febrile illness (AUFI) is the presenting symptom of various tropical and infectious diseases. Viral infection is generally the most common cause of AUFI, accounting for 8&ndash;11.8% of cases; thus, antibiotics might be unnecessary. Dengue and malaria are common tropical infectious diseases requiring effective supportive treatment and antimalarial agents, respectively. The uncertainty of early diagnosis results in widespread empirical antimicrobial treatment in high -income as well as in low-and middle-income countries. Although rapid diagnostic tests (RDTs) have been shown to limit antibiotic prescriptions in dengue and malaria, we observed a wide range of antibiotic prescriptions for 13&ndash;92.7% of cases in previous literature, particularly in RDT-negative malaria cases. Given several RDT limitations, antimicrobial stewardship (AMS) appears to be an effective strategy for controlling unnecessary antibiotic use and antimicrobial resistance (AMR) prevention. This program should be endorsed by a multidisciplinary team in tropical diseases to control collateral damage of inappropriate antimicrobial use. Empirical antibiotic treatment should be administered based on clinical judgement, microbiological evidence, and local epidemiological data. Rapid termination of antibiotic therapy, including disease control or elimination, is the mainstay of AMS in tropical diseases. Local and international sectors should implement an AMS programme to reduce AMR in the Tropics

Treatment-Seeking Behaviors and Knowledge, Attitude and Practices among Suspected Dengue Adult Patients at the Hospital for Tropical Diseases, Bangkok, Thailand

Dengue infection is a major public health problem in Thailand with an increasing incidence in the adult population. Patients&rsquo; knowledge, attitude and practices (KAP) with regarding dengue infection have direct influences on treatment-seeking behaviors and clinical outcomes. We conducted a cross-sectional study to assess the KAP and treatment-seeking behaviors of suspected dengue adult patients attending the Hospital for Tropical Diseases (HTD) in Bangkok, from March 2014 to February 2015. Among 167 participants, the majority of participants (87.9%) were unaware of dengue infection and most of them reported initial self-medication (95.2%). The mean days of fever before attending to the HTD was 4.9 &plusmn; 1.7 days. Outpatient cases reported seeking care significantly earlier than inpatient cases (mean: 3.1 days vs. 5.0 days; p &lt; 0.001). The majority of patients believed that dengue infection has a high mortality rate (63%) and must be treated in hospital (91.3%), highlighting the lack of understanding and misperceptions regarding dengue-related knowledge in the general population. Patients who reported recent or current dengue infection in their family or neighborhood sought medical care early and reported good preventive practices. Health education should focus on the adult population to improve awareness of dengue symptoms and promote early treatment-seeking behavior

Diagnostic Performance of Dengue NS1 and Antibodies by Serum Concentration Technique

Dengue infection has been a public health problem worldwide, especially in tropical areas. A lack of sensitive diagnostic methods in the early phase of the illness is one of the challenging problems in clinical practices. We, herein, analyzed 86 sera of acute febrile patients, from both dengue and non-dengue febrile illness, to study the diagnostic performance of dengue diagnostics. When compared with detection by Polymerase Chain Reaction (PCR), dengue NS1 detection by enzyme-linked immunosorbent assay (ELISA) had the highest sensitivity of 82.4% (with 94.3% specificity), while NS1 by rapid diagnostic test (RDT) had 76.5% sensitivity. IgM detection by ELISA and RDT showed only 27.5% and 17.9% sensitivity, respectively. The combination of NS1 and IgM in RDT yielded a sensitivity of 78.4%, with 97.1% specificity. One of the essential steps in making a diagnosis from patient samples is the preparation process. At present, a variety of techniques have been used to increase the number of analytes in clinical samples. In this study, we focused on the sample concentration method. The sera were concentrated three times with the ultrafiltration method using a 10 kDa molecular weight cut-off membrane. The results showed an increase in the sensitivity of RDT-NS1 detection at 80.4%, with 100% specificity. When combining NS1 and IgM detection, the concentration method granted RDT an 82.4% sensitivity, with 100% specificity. In conclusion, serum concentration by the ultrafiltration method is a simple and applicable technique. It could increase the diagnostic performance of point-of-care dengue diagnostics

Severity of COVID-19 in Patients with Diarrhoea: A Systematic Review and Meta-Analysis

COVID-19 patients occasionally present with diarrhoea. Our objective was to estimate the risk of developing the severe disease in COVID-19 patients with and without diarrhoea and to provide a more precise estimate of the prevalence of COVID-19-associated digestive symptoms. A total of 88 studies (n = 67,794) on patients with a COVID-19 infection published between 1 January 2020 and 20 October 2022 were included in this meta-analysis. The overall prevalence of digestive symptoms was 27% (95% confidence interval (CI): 21&ndash;34%; I2 = 99%). According to our data, the pooled prevalence of diarrhoea symptoms in the 88 studies analysed was 17% (95% CI: 14&ndash;20%; I2 = 98%). The pooled estimate of nausea or vomiting in a total of 60 studies was 12% (95% CI: 8&ndash;15%; I2 = 98%). We also analysed 23 studies with eligible individuals (n = 3800) to assess the association between the disease severity and diarrhoea. Individuals who had diarrhoea were more likely to have experienced severe COVID-19 (odds ratio: 1.71; 95% CI: 1.31&ndash;2.24; p &lt; 0.0001; I2 = 10%). Gastrointestinal symptoms and diarrhoea are frequently presenting COVID-19 manifestations that physicians should be aware of