Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BACKGROUND: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. METHODS: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. RESULTS: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). CONCLUSION: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

Association of Biosecurity and Hygiene Practices with Environmental Contamination with Influenza A Viruses in Live Bird Markets, Bangladesh.

In Bangladesh, live bird market environments are frequently contaminated with avian influenza viruses. Shop-level biosecurity practices might increase risk for environmental contamination. We sought to determine which shop-level biosecurity practices were associated with environmental contamination. We surveyed 800 poultry shops to describe biosecurity practices and collect environmental samples. Samples from 205 (26%) shops were positive for influenza A viral RNA, 108 (14%) for H9, and 60 (8%) for H5. Shops that slaughtered poultry, kept poultry overnight, remained open without rest days, had uneven muddy floors, held poultry on the floor, and housed sick and healthy poultry together were more frequently positive for influenza A viruses. Reported monthly cleaning seemed protective, but disinfection practices were not otherwise associated with influenza A virus detection. Slaughtering, keeping poultry overnight, weekly rest days, infrastructure, and disinfection practices could be targets for interventions to reduce environmental contamination.

Immunogenicity and Viral Shedding of Russian-Backbone, Seasonal, Trivalent, Live, Attenuated Influenza Vaccine in a Phase II, Randomized, Placebo-Controlled Trial Among Preschool-Aged Children in Urban Bangladesh.

BACKGROUND: We evaluated a Russian-backbone, live, attenuated influenza vaccine (LAIV) for immunogenicity and viral shedding in a randomized, placebo-controlled trial among Bangladeshi children. METHODS: Healthy children received a single, intranasal dose of LAIV containing the 2011-2012 recommended formulation or placebo. Nasopharyngeal wash (NPW) specimens were collected on days 0, 2, 4, and 7. Reverse transcription polymerase chain reactions and sequencing identified the influenza virus (vaccine or wild-type). On days 0 and 21, blood specimens were collected to assess immunogenicity using hemagglutination inhibition, microneutralization, and immunoglobulin A (IgA) and G enzyme-linked immunosorbent assays (ELISAs); NPW specimens were also collected to assess mucosal immunogenicity using kinetic IgA ELISA. RESULTS: We enrolled 300 children aged 24 through 59 months in the immunogenicity and viral shedding analyses. Among children receiving LAIV, 45% and 67% shed A/H3N2 and B vaccine strains, respectively. No child shed A/H1N1 vaccine strain. There were significantly higher day 21 geometric mean titers (GMTs) for the LAIV, as compared to the placebo groups, in all immunoassays for A/H3N2 and B (log10 titer P < .0001; GMT Ratio >2.0). Among immunoassays for A/H1N1, only the mucosal IgA GMT was significantly higher than placebo at day 21 (log10 titer P = .0465). CONCLUSIONS: Children vaccinated with LAIV had serum and mucosal antibody responses to A/H3N2 and B, but only a mucosal IgA response to A/H1N1. Many children shed A/H3N2 and B vaccine strains, but none shed A/H1N1. More research is needed to determine the reason for decreased LAIV A/H1N1 immunogenicity and virus shedding. CLINICAL TRIALS REGISTRATION: NCT01625689.

Isolation and Full-Genome Characterization of Nipah Viruses from Bats, Bangladesh.

Despite molecular and serologic evidence of Nipah virus in bats from various locations, attempts to isolate live virus have been largely unsuccessful. We report isolation and full-genome characterization of 10 Nipah virus isolates from Pteropus medius bats sampled in Bangladesh during 2013 and 2014.

Effect of probiotic interventions on depressive symptoms: A narrative review evaluating systematic reviews.

Depression is one of the most prevalent mental illnesses and is often associated with various other medical disorders. Since the 1980s, the primary pharmacological treatment has been antidepressants, but due to the recent discovery of the association between the gut microbiome and mental health, probiotics have been proposed as an adjunctive or alternate treatment. In this narrative review, we aim to provide a holistic perspective by synthesizing and evaluating existing evidence, discussing key biological mechanisms, exploring the history of probiotic use, and appreciating the influence of modern diet on mental health. Five online databases were searched for relevant studies up to December 2017. Systematic reviews that included randomized controlled trials assessing the efficacy of probiotics in the treatment of depressive symptoms were included. Seven systematic reviews met the inclusion criteria. Three of these reviews conducted meta-analyses, out of which, two concluded that probiotics improved depressive symptoms in the sample population. Out of the four reviews that conducted qualitative analysis, three reviews concluded that probiotics have the potential to be used as a treatment. Due to the differences in clinical trials, a definitive effect of probiotics on depressive symptoms cannot be concluded. Nonetheless, probiotics seem to potentially produce a significant therapeutic effect for subjects with pre-existing depressive symptoms. Further studies are warranted for definitive conclusions.

Nipah virus disease: what can we do to improve patient care?

The year 2023 marked the 25th anniversary of the first detected outbreak of Nipah virus disease. Despite Nipah virus being a priority pathogen in the WHO Research and Development blueprint, the disease it causes still carries high mortality, unchanged since the first reported outbreaks. Although candidate vaccines for Nipah virus disease exist, developing new therapeutics has been underinvested. Nipah virus disease illustrates the typical market failure of medicine development for a high-consequence pathogen. The unpredictability of outbreaks and low number of infections affecting populations in low-income countries does not make an attractive business case for developing treatments for Nipah virus disease-a situation compounded by methodological challenges in clinical trial design. Nipah virus therapeutics development is not motivated by commercial interest. Therefore, we propose a regionally led, patient-centred, and public health-centred, end-to-end framework that articulates a public health vision and a roadmap for research, development, manufacturing, and access towards the goal of improving patient outcomes. This framework includes co-creating a regulatory-compliant, clinically meaningful, and context-specific clinical development plan and establishing quality standards in clinical care and research capabilities at sites where the disease occurs. The success of this approach will be measured by the availability and accessibility of improved Nipah virus treatments in affected communities and reduced mortality.

The role of circulating cell-free DNA and its integrity as a biomarker for diagnosis of breast cancer using ALU (247/115) bP sequences.

Diagnosis of breast cancer by using sensitive and specific biomarkers is necessary. Cell- free DNA (cf-DNA) is a candidate biomarker in various cancers. Contrasting, shorted uniformed DNA released from apoptotic non-diseased cells, DNA released from malignant cells varies in size. DNA integrity is a ratio between 247 and 115 bp. This study aimed to evaluate the diagnostic values of cf-DNA using ALU -247 and ALU- 115 and DNA integrity in peripheral blood of breast cancer patients as a noninvasive marker. Also, to determine correlations between ALU-247 and ALU-115, DNA integrity, cancer antigen (CA )15-3 and carcinoembryonic antigen (CEA) with each other in breast cancer patients and in different stages of breast cancer. This study included 100 females, divided into 3 groups. The first group consisted of 20 apparently healthy females as the control group. The second group included 20 patients with benign breast lesions. The third group included 60 patients with breast cancer. Serum levels of both ALU-247 and ALU-115 as well as cf-DNA integrity were statistically significant higher in breast cancer patients as compared to the control group (p=0.018, p < 0.001 and p=0.009 respectively). Compared to the control group, ALU-247 had the best diagnostic sensitivity for diagnosis of breast cancer (86.78%) with 75% specificity with area under the curve of 0.848. We concluded that measuring ALU-247, ALU-115 and DNA integrity in peripheral blood would be a promising novel approach for diagnosis and early detection of breast cancer.

Genetic alterations of Keap1 confers chemotherapeutic resistance through functional activation of Nrf2 and Notch pathway in head and neck squamous cell carcinoma.

Keap1 mutations regulate Nrf2 activity and lead to chemoresistance in cancers. Yet the underlying molecular mechanisms of chemoresistance are poorly explored. By focusing and genotyping head and neck squamous cell carcinoma (HNSCC) that had available pathologic and clinical data, we provide evidence that Keap1 displays frequent alterations (17%) in HNSCC. Functional loss of Keap1 results in significant activation of Nrf2 and promotes cancer cell growth, proliferation, and elevated cancer stem cell (CSCs) self-renewal efficiency and resistance to oxidative stress. Furthermore, decreased Keap1 activity in these cells increased nuclear accumulation of Nrf2 and activation of the Notch pathway, causing enhanced transcriptional alterations of antioxidants, xenobiotic metabolism enzymes, and resistance to chemotherapeutic treatment. Limiting the Nrf2 activity by either Keap1 complementation or by Nrf2 silencing increased the sensitivity to chemotherapy in Keap1-mutated cells and repressed the CSC self-renewal activity. Our findings suggest that Keap1 mutations define a distinct disease phenotype and the Keap1-Nrf2 pathway is one of the leading molecular mechanisms for clinical chemotherapeutic resistance. Targeting this pathway may provide a potential and attractive personalized treatment strategy for overcoming chemotherapeutic resistance conferred by Keap1 mutations.

Major zoonotic diseases of public health importance in Bangladesh.

Zoonotic diseases cause repeated outbreaks in humans globally. The majority of emerging infections in humans are zoonotic. COVID-19 is an ideal example of a recently identified emerging zoonotic disease, causing a global pandemic. Anthropogenic factors such as modernisation of agriculture and livestock farming, wildlife hunting, the destruction of wild animal habitats, mixing wild and domestic animals, wildlife trading, changing food habits and urbanisation could drive the emergence of zoonotic diseases in humans. Since 2001, Bangladesh has been reporting many emerging zoonotic disease outbreaks such as nipah, highly pathogenic avian influenza, pandemic H1N1, and COVID-19. There are many other potential zoonotic pathogens such as Ebola, Middle East respiratory syndrome coronavirus, Kyasanur forest disease virus and Crimean-Congo haemorrhagic fever that may emerge in the future. However, we have a limited understanding of zoonotic diseases' overall risk in humans and associated factors that drive the emergence of zoonotic pathogens. This narrative review summarised the major emerging, re-emerging, neglected and other potential zoonotic diseases in Bangladesh and their associated risk factors. Nipah virus and Bacillus anthracis caused repeated outbreaks in humans. More than 300 human cases with Nipah virus infection were reported since the first outbreak in 2001. The highly pathogenic avian influenza virus (H5N1) caused more than 550 outbreaks in poultry, and eight human cases were reported so far since 2007. People of Bangladesh are frequently exposed to zoonotic pathogens due to close interaction with domestic and peri-domestic animals. The rapidly changing intensified animal-human-ecosystem interfaces and risky practices increase the risk of zoonotic disease transmission. The narrative review's findings are useful to draw attention to the risk and emergence of zoonotic diseases to public health policymakers in Bangladesh and the application of one-health approach to address this public health threat.

Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.

The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.

An outbreak of classical swine fever in pigs in Bangladesh, 2015.

In a group of 22 healthy pigs aged between 4 and 6 months, 2 pigs became ill with high fever, complete anorexia, cough and abnormal swaying movements on 22 June 2015. One of them died on June 24 and the second died on July 3. Shortly after, the remaining pigs also fell ill and died from the same illness by 10 August 2015. We investigated the aetiology, epidemiological and clinical features of the outbreak. We recorded the clinical signs and symptoms for each pig with the date of onset of illness. Veterinarians conducted post-mortem examinations on the 12 dead pigs, they collected tissue samples from the dead pigs and placed them in a tube containing 1 mL of nucleic acid extraction buffer (lysis buffer). We tested all the tissue samples by real-time reverse transcription polymerase chain reaction (rRT-PCR) to detect classical swine fever virus (CSFV) because the animals' symptoms matched those of this disease. We also conducted a phylogentic analysis of the nucleotide sequence of the E2 gene segment of CSFV detected in a lung tissue sample. The attack rate (22/22) and the case fatality were 100%. The predominant symptoms of the disease included high fever, cough, diarrhoea and swaying movements of the hind legs prior to death. Of the 12 pigs tissue samples tested, all had evidence of the presence of CSFV RNA by rRT-PCR. The phylogenetic analysis indicated that the virus belongs to genotype 2.2, which is closely related to CSFV genotype 2.2 reported in India. Our investigation suggests that CSF is circulating in pigs, posing a risk for communities in Bangladesh that rely on pigs for economic income and dietary protein. Future research could focus on estimating the disease and economic burden of CSFV in pig rearing areas to determine if interventions might be warranted or cost-effective.

Epidemiology and genetic characterization of Peste des petits ruminants virus in Bangladesh.

Peste des petits ruminants (PPR) is an acute, highly contagious disease responsible for high morbidity and mortality rates in susceptible sheep and goats. Adequate knowledge of the diversity of circulating strains of PPR virus will help livestock authorities choose appropriate vaccines. The objective of this study was to describe the epidemiology of PPR and characterize the strains circulating in Bangladesh. Veterinarians enrolled goats showing signs consistent with PPR, including diarrhoea, fever and respiratory distress, from three veterinary hospitals. Post-treatment follow up was carried out to ascertain health outcomes of the goats. Faecal and throat swab samples were collected from the goats and tested for PPRV RNA using real-time reverse transcription polymerase chain reaction (rRT-PCR). Nucleotide sequence-based phylogenetic analyses of two structural genes, the nucleocapsid (N gene), and the haemagglutinin (H gene) were studied to determine the genetic variations of PPRV strains. Of the 539 goats enrolled, 38% (203/539) had detectable RNA for PPRV. We were able to follow up with 91% (184/203) of the PPRV infected goats; 44 of them died (24%). PPRV was more frequently identified in the summer (45%) than in the rainy season (29%) (Odds ratio = 1.9, 95% confidence interval: 1.3-3.1). Bangladeshi strains were phylogenetically similar to the lineage IV PPRV strains; showing particularly strong affiliation with Tibetan and Indian strains. PPR is a common viral infection of the goats in Bangladesh, with a high case-fatality rate. This study confirms the circulation of lineage IV PPRV in the country with unique amino acid substitutions in N and H proteins and provides baseline data for vaccine development and implementation.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

INTRODUCTION: Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. MATERIAL AND METHODS: We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. RESULTS: Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. CONCLUSIONS: In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.

Axillary breast tissue mistaken for suppurative hidradenitis: an avoidable error.

The differential diagnosis for a solitary axillary mass is extensive. Based on the initial history and physical examination of the patient presented in this case report, the diagnosis of suppurative hidradenitis was incorrectly reached. This subjected her to a surgical procedure that was not indicated for the actual diagnosis of ectopic axillary breast tissue. This article reviews the workup for a solitary axillary mass and discusses multiple aspects of ectopic breast tissue.

Challenges to evaluating respiratory syncytial virus mortality in Bangladesh, 2004-2008.

BACKGROUND: Acute lower respiratory illness is the most common cause of death among children, globally. Data are not available to make accurate estimates on the global mortality from respiratory syncytial virus (RSV), specifically. METHODS: Respiratory samples collected from children under 5 years of age during 2004 to 2008 as part of population-based respiratory disease surveillance in an urban community in Dhaka, Bangladesh were tested for RSV, human metapneumovirus (HMPV), human parainfluenza virus (PIV) types 1, 2, and 3, influenza and adenovirus by RT-PCR. Verbal autopsy data were used to identify children who died from respiratory illness in a nearby rural community. Significance of the correlation between detections and community respiratory deaths was determined using Spearman's coefficient. RESULTS: RSV activity occurred during defined periods lasting approximately three months but with no clear seasonal pattern. There was no significant correlation between respiratory deaths and detection of any of the respiratory viruses studied. CONCLUSION: Outbreaks of respiratory viruses may not be associated with deaths in children in the study site; however, the few respiratory deaths observed and community-to-community variation in the timing of outbreaks may have obscured an association. An accurate assessment of respiratory virus-associated deaths will require detections and death data to come from the same location and a larger study population.

Evidence of interspecies O antigen gene cluster transfer between Shigella boydii 15 and Escherichia fergusonii.

An environmental bacterial isolate, Iso10, previously found to show serological cross-reactivity with type-specific Shigella boydii 15 antisera was subjected to further molecular and serological analyses that revealed interspecies transfer of the O antigen gene cluster. Western blot analysis of Iso10 cell surface extracts and purified lipopolysaccharides demonstrated strong cross-reactivity with S. boydii 15-specific monovalent antisera and a lipopolysaccharide gel banding profile similar to that of S. boydii 15. Biochemical and phylogenetic analyses identified the Iso10 isolate as Escherichia fergusonii. O antigen gene cluster analyses of Iso10, carried out by restriction fragment length analysis of the amplified ~10-kb O antigen-encoding gene cluster, revealed a profile highly similar to that of S. boydii 15, confirming the presence of the S. boydii 15 somatic antigen in Iso10. To the best of our knowledge, this is the first report of interspecies transfer of O antigen-encoding genes between S. boydii and E. fergusonii, and it has implications for our understanding of the role of lateral gene transfer in the emergence of novel Shigella serotypes.

Chemical and biological investigations of Delonix regia (Bojer ex Hook.) Raf.

In this study, five compounds, lupeol (1), epilupeol (2), ß-sitosterol (3), stigmasterol (4) and p-methoxybenzaldehyde (5) were isolated from the petroleum ether and dichloromethane fractions of a methanolic extract of the stem bark of Delonix regia. Antimicrobial screening of the different extracts (15 µg mm-2) was conducted by the disc diffusion method. The zones of inhibition demonstrated by the petroleum ether, carbon tetrachloride and dichloromethane fractions ranged from 9-14 mm, 11-13 mm and 9-20 mm, respectively, compared to kanamycin standard with the zone of inhibition of 20-25 mm. In brine shrimp lethality bioassay, the carbon tetrachloride soluble materials demonstrated the highest toxicity with LC50 of 0.83 µg mL-1, while petroleum ether and dichloromethane soluble partitionates of the methanolic extract revealed LC50 of 14.94 and 3.29 µg mL-1, respectively, in comparison with standard vincristine sulphate with LC50 of 0.812 µg mL-1. This is the first report on compounds separation from D. regia, their antimicrobial activity and cytotoxicity.