Streamlined detection of Nipah virus antibodies using a split NanoLuc biosensor.

Nipah virus (NiV) is an emerging zoonotic RNA virus that can cause fatal respiratory and neurological diseases in animals and humans. Accurate NiV diagnostics and surveillance tools are crucial for the identification of acute and resolved infections and to improve our understanding of NiV transmission and circulation. Here, we have developed and validated a split NanoLuc luciferase NiV glycoprotein (G) biosensor for detecting antibodies in clinical and animal samples. This assay is performed by simply mixing reagents and measuring luminescence, which depends on the complementation of the split NanoLuc luciferase G biosensor following its binding to antibodies. This anti-NiV-G "mix-and-read" assay was validated using the WHO's first international standard for anti-NiV antibodies and more than 700 serum samples from the NiV-endemic country of Bangladesh. Anti-NiV antibodies from survivors persisted for at least 8 years according to both ⍺NiV-G mix-and-read and NiV neutralization assays. The ⍺NiV-G mix-and-read assay sensitivity (98.6%) and specificity (100%) were comparable to anti-NiV IgG ELISA performance but failed to detect anti-NiV antibodies in samples collected less than a week following the appearance of symptoms. Overall, the anti-NiV-G biosensor represents a simple, fast, and reliable tool that could support the expansion of NiV surveillance and retrospective outbreak investigations.

Detection of Rotavirus in Respiratory Specimens From Bangladeshi Children Aged <2 Years Hospitalized for Acute Gastroenteritis.

To examine the potential for respiratory transmission of rotavirus, we systematically assessed if rotavirus RNA is detectable by real-time quantitative reverse transcription-polymerase chain reaction from nasal and oropharyngeal swab specimens of Bangladeshi children with acute rotavirus gastroenteritis. Forehead swabs were collected to assess skin contamination. Among 399 children aged <2 years hospitalized for gastroenteritis during peak rotavirus season, rotavirus RNA was detected in stool, oral, nasal and forehead swab specimens of 354 (89%). A subset was genotyped; genotype was concordant within a child's specimen set and several different genotypes were detected across children. These findings support possible respiratory transmission of rotavirus and warrant further investigation.

In silico prediction of interaction between Nipah virus attachment glycoprotein and host cell receptors Ephrin-B2 and Ephrin-B3 in domestic and peridomestic mammals.

Nipah virus (NiV) is a lethal bat-borne zoonotic virus that causes mild to acute respiratory distress and neurological manifestations in humans with a high mortality rate. NiV transmission to humans occurs via consumption of bat-contaminated fruit and date palm sap (DPS), or through direct contact with infected individuals and livestock. Since NiV outbreaks were first reported in pigs from Malaysia and Singapore, non-neutralizing antibodies against NiV attachment Glycoprotein (G) have also been detected in a few domestic mammals. NiV infection is initiated after NiV G binds to the host cell receptors Ephrin-B2 and Ephrin-B3. In this study, we assessed the degree of NiV host tropism in domestic and peridomestic mammals commonly found in Bangladesh that may be crucial in the transmission of NiV by serving as intermediate hosts. We carried out a protein-protein docking analysis of NiV G complexes (n = 52) with Ephrin-B2 and B3 of 13 domestic and peridomestic species using bioinformatics tools. Protein models were generated by homology modelling and the structures were validated for model quality. The different protein-protein complexes in this study were stable, and their binding affinity (ΔG) scores ranged between -8.0 to -19.1 kcal/mol. NiV Bangladesh (NiV-B) strain displayed stronger binding to Ephrin receptors, especially with Ephrin-B3 than the NiV Malaysia (NiV-M) strain, correlating with the observed higher pathogenicity of NiV-B strains. From the docking result, we found that Ephrin receptors of domestic rat (R. norvegicus) had a higher binding affinity for NiV G, suggesting greater susceptibility to NiV infections compared to other study species. Investigations for NiV exposure to domestic/peridomestic animals will help us knowing more the possible role of rats and other animals as intermediate hosts of NiV and would improve future NiV outbreak control and prevention in humans and domestic animals.

Tackling a global epidemic threat: Nipah surveillance in Bangladesh, 2006-2021.

Human Nipah virus (NiV) infection is an epidemic-prone disease and since the first recognized outbreak in Bangladesh in 2001, human infections have been detected almost every year. Due to its high case fatality rate and public health importance, a hospital-based Nipah sentinel surveillance was established in Bangladesh to promptly detect Nipah cases and respond to outbreaks at the earliest. The surveillance has been ongoing till present. The hospital-based sentinel surveillance was conducted at ten strategically chosen tertiary care hospitals distributed throughout Bangladesh. The surveillance staff ensured that routine screening, enrollment, data, and specimen collection from suspected Nipah cases were conducted daily. The specimens were then processed and transported to the reference laboratory of Institute of Epidemiology, Disease Control and Research (IEDCR) and icddr,b for confirmation of diagnosis through serology and molecular detection. From 2006 to 2021, through this hospital-based surveillance platform, 7,150 individuals were enrolled and tested for Nipah virus. Since 2001, 322 Nipah infections were identified in Bangladesh, 75% of whom were laboratory confirmed cases. Half of the reported cases were primary cases (162/322) having an established history of consuming raw date palm sap (DPS) or tari (fermented date palm sap) and 29% were infected through person-to-person transmission. Since the initiation of surveillance, 68% (218/322) of Nipah cases from Bangladesh have been identified from various parts of the country. Fever, vomiting, headache, fatigue, and increased salivation were the most common symptoms among enrolled Nipah patients. Till 2021, the overall case fatality rate of NiV infection in Bangladesh was 71%. This article emphasizes that the overall epidemiology of Nipah virus infection in Bangladesh has remained consistent throughout the years. This is the only systematic surveillance to detect human NiV infection globally. The findings from this surveillance have contributed to early detection of NiV cases in hospital settings, understanding of Nipah disease epidemiology, and have enabled timely public health interventions for prevention and containment of NiV infection. Although we still have much to learn regarding the transmission dynamics and risk factors of human NiV infection, surveillance has played a significant role in advancing our knowledge in this regard.

COVID-19 Risk Perception and Prevention Practices among High- and Low-Density Populations in Bangladesh: A Mixed-Methods Study.

We aimed to explore coronavirus disease 2019 (COVID-19) risk perception and prevention practices among people living in high- and low-population density areas in Dhaka, Bangladesh. A total of 623 patients with confirmed COVID-19 agreed to participate in the survey. Additionally, we purposively selected 14 participants from diverse economic and occupational groups and conducted qualitative interviews for them accordingly. Approximately 70% of the respondents had low socioeconomic status. Among the 623 respondents, 146 were from low-density areas, and 477 were from high-density areas. The findings showed that study participants perceived COVID-19 as a punishment from the Almighty, especially for non-Muslims, and were not concerned about its severity. They also believed that coronavirus would not survive in hot temperatures or negatively impact Bangladeshis. This study revealed that people were reluctant to undergo COVID-19 testing. Family members hid if anyone tested positive for COVID-19 or did not adhere to institutional isolation. The findings showed that participants were not concerned about COVID-19 and believed that coronavirus would not have a devastating impact on Bangladeshis; thus, they were reluctant to follow prevention measures and undergo testing. Tailored interventions for specific targeted groups would be relevant in mitigating the prevailing misconceptions.

Antibiotic Prescribing Practices for Treating COVID-19 Patients in Bangladesh.

Although national and international guidelines have strongly discouraged use of antibiotics to treat COVID-19 patients with mild or moderate symptoms, antibiotics are frequently being used. This study aimed to determine antibiotics-prescribing practices among Bangladeshi physicians in treating COVID-19 patients. We conducted a cross-sectional survey among physicians involved in treating COVID-19 patients. During September-November 2021, data were collected from 511 respondents through an online Google Form and hardcopies of self-administered questionnaires. We used descriptive statistics and a regression model to identify the prevalence of prescribing antibiotics among physicians and associated factors influencing their decision making. Out of 511 enrolled physicians, 94.13% prescribed antibiotics to COVID-19 patients irrespective of disease severity. All physicians working in COVID-19-dedicated hospitals and 87% for those working in outpatient wards used antibiotics to treat COVID-19 patients. The majority (90%) of physicians reported that antibiotics should be given to COVID-19 patients with underlying respiratory conditions. The most prescribed antibiotics were meropenem, moxifloxacin, and azithromycin. Our study demonstrated high use of antibiotics for treatment of COVID-19 patients irrespective of disease severity and the duty ward of study physicians. Evidence-based interventions to promote judicious use of antibiotics for treating COVID-19 patients in Bangladesh may help in reducing an overuse of antibiotics.

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June−September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 (p = 0.01) and 28 (p = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable (p > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.

Vertical Transfer of Humoral Immunity against Nipah Virus: A Novel Evidence from Bangladesh.

A major obstacle to in-depth investigation of the immune response against Nipah virus (NiV) infection is its rapid progression and high mortality rate. This paper described novel information on the vertical transfer of immune properties. In January 2020, a female aged below five years and her mother from Faridpur district of Bangladesh were infected. Both had a history of raw date palm sap consumption and were diagnosed as confirmed NiV cases. The daughter passed away, and the mother survived with significant residual neurological impairment. She conceived one and a half year later and was under thorough antenatal follow-up by the surveillance authority. A healthy male baby was born. As part of routine survivor follow-up, specimens were collected from the newborn and tested for NiV infection at the reference laboratory to exclude vertical transmission. Although testing negative for anti-Nipah IgM and PCR for NiV, a high titre of anti-Nipah IgG was observed. The transfer of humoral immunity against NiV from mother to neonate was confirmed for the first time. The article will serve as a reference for further exploration regarding NiV-specific antibodies that are transferred through the placenta, their potential to protect newborns, and how this may influence vaccine recommendations.

The economic burden of rotavirus hospitalization among children < 5 years of age in selected hospitals in Bangladesh.

BACKGROUND: Rotavirus is a common cause of severe acute gastroenteritis among young children. Estimation of the economic burden would provide informed decision about investment on prevention strategies (e.g., vaccine and/or behavior change), which has been a potential policy discussion in Bangladesh for several years. METHODS: We estimated the societal costs of children <5 years for hospitalization from rotavirus gastroenteritis (RVGE) and incidences of catastrophic health expenditure. A total of 360 children with stool specimens positive for rotavirus were included in this study from 6 tertiary hospitals (3 public and 3 private). We interviewed the caregiver of the patient and hospital staff to collect cost from patient and health facility perspectives. We estimated the economic cost considering 2015 as the reference year. RESULTS: The total societal per-patient costs to treat RVGE in the public hospital were 126 USD (95% CI: 116-136) and total household costs were 161 USD (95% CI: 145-177) in private facilities. Direct costs constituted 38.1% of total household costs. The out-of-pocket payments for RVGE hospitalization was 23% of monthly income and 76% of households faced catastrophic healthcare expenditures due to this expense. The estimated total annual household treatment cost for the country was 10 million USD. CONCLUSIONS: A substantial economic burden of RVGE in Bangladesh was observed in this study. Any prevention of RVGE through cost-effective vaccination or/and behavioural change would contribute to substantial economic benefits to Bangladesh.

Prevalence of COVID-19 in Bangladesh, April to October 2020-a cross-sectional study.

Objective: The aim of this study was to estimate the proportion of symptomatic and asymptomatic laboratory-confirmed coronavirus disease 2019 (COVID-19) cases among the population of Bangladesh. Methods: A cross-sectional survey was conducted in Dhaka City and other districts of Bangladesh between April 18 and October 12, 2020. A total of 32 districts outside Dhaka were randomly selected, and one village and one mahalla was selected from each district; 25 mahallas were selected from Dhaka City. From each village or mahalla, 120 households were enrolled through systematic random sampling. Results: A total of 44 865 individuals were interviewed from 10 907 households. The majority (70%, n = 31 488) of the individuals were <40 years of age. Almost half of the individuals (49%, n = 21 888) reported more than four members in their household. It was estimated that 12.6% (n = 160) of the households had one or more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals, among whom 0.9% (n = 404) of individuals had at least one COVID-19-like symptom, at the national level. The prevalence of COVID-19 in the general population was 6.4%. Among the SARS-CoV-2-positive individuals, 87% were asymptomatic. Conclusions: The substantial high number of asymptomatic cases all over Bangladesh suggests that community-level containment and mitigation measures are required to combat COVID-19. Future studies to understand the transmission capability could help to define mitigation and control measures.