•Ivermectin, an FDA-approved anti-parasitic agent, was found to be an inhibitor of SARS-CoV-2 replication in the laboratory.•Ivermectin may be effective for the treatment of early-onset mild COVID-19 ...in adult patients.•Early viral clearance of SARS-CoV-2 was observed in ivermectin treated patients.•Remission of fever, cough and sore throat did not differ among treatment groups. No severe adverse event was observed.•Larger trials will be needed to confirm these preliminary findings.
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) ...detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.
Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, ...antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance.
This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers.
We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis.
A total of 301 antibiotic dispensers were identified, of whom 92% (
= 278) were private and 8% (
= 23) public. 52% (
= 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician's prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies' information.
Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.
Objectives: To assess the safety and reactogenicity of single oral dose of heat-stable rotavirus vaccine (HSRV) in healthy adults aged 18-45 years followed by assessment of safety, reactogenicity, ...and immunogenicity of three doses of HSRV in healthy infants aged 6-8 weeks at enrollment.
Trial Design: Single-center randomized controlled, sequential, blinded (adults) and open-label (infants).
Setting: Single site at International Center for Diarrheal Disease Research, Bangladesh (icddr,b).
Participants: Fifty eligible adults randomized in 1:1 ratio (HSRV: Placebo) followed by 50 eligible infants randomized in 1:1 ratio (HSRV: Comparator (RotaTeq®, pentavalent human-bovine (WC3) reassortant live-attenuated, rotavirus vaccine)).
Intervention: Adults received either a single dose of HSRV or placebo and followed for 14 days. Infants received three doses of either HSRV or comparator with a follow-up for 28 days after each dose.
Main Outcome Measures: Solicited and unsolicited adverse events (AEs) along with any serious adverse events (SAEs) were part of the safety and reactogenicity assessment in adults and infants whereas serum anti-rotavirus IgA response rates were part of immunogenicity assessment in infants only. Post-vaccination fecal shedding of vaccine-virus rotavirus strains was also determined in adults and infants.
Results: In this study, HSRV, when compared with placebo, did not result in increase in solicited adverse events (solicited AEs) in adults. In infants, HSRV had a safety profile similar to comparator vis-à-vis solicited AEs. In infants, fecal shedding of vaccine-virus strains was not detected in HSRV recipients but was observed in two comparator recipients. Percentage of infants exhibiting threefold rise in serum anti-rotavirus IgA titers from baseline to 1-month post-dose 3 in HSRV group was 88% (22/25) and 84% (21/25) in comparator group.
Conclusion: HSRV was found to be generally well-tolerated in both adults and infants and immunogenic in infants.
Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated ...antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate.
Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use ...practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices.
We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions.
Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia.
Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance.
Wellcome Trust and Volkswagen Foundation.
We conducted a prospective case-control study to investigate the epidemiology, clinical features, and systemic antibody responses of cryptosporidiosis in Bangladeshi children. Forty-six children ...presenting to the International Center for Diarrheal Disease Research, Bangladesh in Dhaka, Bangladesh with diarrhea and Cryptosporidium spp. oocysts in the stool were enrolled as cases. Forty-six age-matched children with diarrhea, but without cryptosporidial infection, were enrolled as controls. Thirty cases and 23 controls returned for follow-up three weeks after discharge. Infection with Cryptosporidium spp. occurred most commonly in those less than two years of age, was accompanied by watery diarrhea and vomiting, and was more likely to be associated with persistent diarrhea. Other than duration of diarrhea, there were no significant differences in clinical or epidemiologic features between cases and controls. Cryptosporidium-specific serum IgM levels were significantly higher in cases compared with controls at presentation. In addition, there was a significant increase in serum Cryptosporidium-specific serum IgG levels over the three-week follow-up period in cases compared with controls. Within the case group, there was no difference between children with acute and persistent diarrhea in the change in IgG levels over the follow-up period. However, there was a significant difference between children with acute and persistent diarrhea in changes in both IgA and IgM levels, with persistent diarrhea being associated with a decrease in levels of both antibodies.
Surface water is heavily exposed to contamination as this is the ubiquitous source for most of the water needs. This situation is exaggerated by the excessive population, heavy industrialization, ...rapid urbanization, and improper sanitation. Comprehensive measurement and knowledge extraction of surface water quality is therefore pivotal for ensuring safe and hygienic water use. Consequently, surface water quality profiling has received remarkable academic attention in recent decades that produces an ample amount of research results. This study, therefore, conducts a comprehensive systematic literature review to summarize and structure the existing literature and to identify current research trends and hotspots. Reported results suggest that the terrain of fresh surface water includes 13 distinct water sources that are predominantly used in 5 sectors. These sectors often cause the water pollution in the form of industrial effluents, agricultural runoffs, and domestic sewage. For profiling the water quality, around 23 Water Quality Index (WQI) models, and 10 Pollution Index (PI) models are used in research. These models often use several water quality parameters. This study reports an exhaustive taxonomy of 69 prominent quality parameters in three categories which will support their adoption for these models. Finally, the limitations of the current manual water quality measurement approaches are summarized to propose a set of seven requirements for the tech-intensive water quality profiling research and system development.
•Surface water is heavily exposed to contamination and pollution.•Comprehensive measurement and monitoring surface water quality are pivotal for ensuring safe and hygienic water use.•A review is needed to draw a holistic landscape of surface water, its usage pattern and source of pollution.
Abstract
Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. ...This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.
Hemophilia is one of the commonest inherited bleeding disorders which may lead to chronic bleeding tendencies and life-long disabilities if not properly managed. Knowing the pattern of the disease ...aids in the prevention of disability and improvement of quality of life in hemophilia. However, there is a dearth of literature on the issue in Bangladesh. So, this study was designed to explore the frequency and site of spontaneous bleeding in moderate and severe hemophilia patients visiting in a tertiary level hospital. This descriptive cross-sectional study was conducted at the department of Hematology and Bone Marrow Transplantation (BMT) Center in Dhaka Medical College Hospital, Dhaka between February 2020 and August 2020. A total of 44 diagnosed cases of moderate to severe hemophilia were included in the study according to inclusion criteria. A detailed inquiry of history, thorough physical examination and relevant investigations were done and were recorded in case-record form. Informed written consent was taken from patients or their guardians where appropriate. All procedures were done according to Declaration of Helsinki. After entry and checking, data was analysed using SPSS version 26. Out of 44 participants, 25 (56.8%) and 19 (43.2%) had moderate and severe hemophilia. Mean age of the study population was 21.31 (+ or - 9.78) years with the majority aged between 11 and 20 years (45.5%). All sociodemographic features were similar across severity. Hemophilia A and B was found in 90.9% and 9.1%, respectively. However, all type B patients severe hemophilia making it statistically significantly different from type A (p = 0.029). The median age of first bleeding was 3.5 years and median age of first diagnosis was 5 years. Nevertheless, approximately 67.4% patients were diagnosed as a case of hemophilia at the time of their first diagnosis. The median spontaneous bleedings episodes among all patients was 32 (range: 0-97) which did not different significantly between severe and moderate patients. The most common affected (target) joint was knee joint (88.6%) followed by elbow joint (64%) among all patients. The knee joint was more commonly involved in severe than moderate disease. This study observed the variations in pattern and frequency of spontaneous bleeding in patients with hemophilia. Severe disease was more frequent in hemophilia B than A and knee joint was the most frequent site of bleeding. However, further extensive studies are recommended.
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