5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial.

BACKGROUND: WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. METHODS: We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. FINDINGS: Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. INTERPRETATION: A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. FUNDING: The Bill & Melinda Gates Foundation.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Biovalorization of Fruit Wastes for Development of Biodegradable Antimicrobial Chitosan-Based Coatings for Fruits (Tomatoes and Grapes).

Organic wastes are generated from high consumption of fruits. In this paper, fruit residual wastes collected from fruit-juice centres were transformed into fine powder, and thereafter, proximate analysis along with SEM, EDX and XRD was done to get into the surface morphology, minerals and ash content of fine powder. Aqueous extract (AE) prepared from this powder was studied using gas chromatography-mass spectroscopy (GC-MS). The phytochemicals identified are N-hexadecanoic acid; 1,3-dioxane,2,4-dimethyl-, diglycerol, 4-ethyl-2-hydroxycyclopent-2-en-1-one, eicosanoic acid, etc. AE showed high antioxidant and a low MIC value (2 mg/ml) against Pseudomonas aeruginosa MZ269380. AE having acceptance as nontoxic to biological system, formulation of chitosan (2%)-based coating was done with 1% AQ. Surface coatings of tomatoes and grapes showed significant inhibition of microbial growth even after 10 days of storage at ambient temperature (25 ± 2 °C). Colour, texture, firmness and aceptability of coated fruits showed no degradation compared to negative control. Additionally, the extracts showed insignificance haemolysis of goat RBC and damage of Calf Thymus DNA which exhibited its biocompatible nature. Biovalorization of fruit wastes yields useful phytochemicals and can be utilized in various sectors thereby finding a sustainable solution for disposal of fruit wastes.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Bangladesh.

Background: Shigella is an important cause of diarrhea in Bangladeshi children <5 years of age, with an incidence rate of 4.6 per 100 person-years. However, the report was more than a decade old, and data on Shigella consequences are similarly outdated and heterogeneously collected. Methods: Facility-based disease surveillance is planned to be carried out under the Enterics for Global Health (EFGH) Shigella Surveillance Study consortium for 2 years with aims to optimize and standardize laboratory techniques and healthcare utilization and coverage survey, clinical and anthropometric data collection, safety monitoring and responsiveness, and other related activities. The EFGH is a cohesive network of multidisciplinary experts, capable of operating in concert to conduct the study to generate data that will pave the way for potential Shigella vaccine trials in settings with high disease burden. The study will be conducted within 7 country sites in Asia, Africa, and Latin America. Conclusions: We outline the features of the Bangladesh site as part of this multisite surveillance network to determine an updated incidence rate and document the consequences of Shigella diarrhea in children aged 6-35 months, which will help inform policymakers and to implement the future vaccine trials.

Effects of nZnS vs. nZnO and ZnCl2 on mungbean [Vigna radiata (L.) R. Wilczek] plant and Bradyrhizobium symbiosis: A life cycle study.

Scarce of knowledge of using Zinc (Zn) nanoparticles (NPs) to augment plant growth, Zn availability to plants and its potential toxicity warrants more NPs-plant life cycle studies. The main objectives of this study were to compare nano zinc sulphide (nZnS) with nano zinc oxide (nZnO) and ionic Zn i.e., ZnCl2, as a source of Zn, as well as to establish physiological impact of NPs on growth, yield and symbiosis of mungbean [Vigna radiata (L.) R. Wilczek] plants at different concentrations (0, 0.01, 0.1, 1 and 10 mg kg-1 of soil). In this study, mungbean plants were grown for 60 days (life cycle study) in natural soil infested with Bradyrhizobium. Effects of Zn compounds (nZnS, nZnO and ZnCl2) on plant height, dry biomass, number of nodules per plant, yield and fruit agronomical parameters along with micronutrient assessment were determined. Impact of Zn compounds on Bradyrhizobium-mungbean symbiosis was also unravelled. Results showed that both the NPs, (nZnS and nZnO) were more effective than ZnCl2 in promoting growth and yield up to a critical concentration and above which phytotoxic effects were observed. Both the NPs were more effective than ZnCl2 at increasing fruit Zn content also. Whereas, nZnS treatment was found to be better than nZnO in improving overall plant growth. Bradyrhizobium-mungbean symbiosis was not affected at lower NPs concentrations, while higher concentration revealed toxicity by damaging bacterial morphology and nodule formation. There was no nano specific toxicity found while, ZnCl2 showed relatively more toxicity than both the NPs. The present investigation demonstrated the concept of nano-micronutrient as well as NPs phytotoxicity by understanding NPs-plant interactions in the soil environment.

Cost-effective remedial to microfiber pollution from wash effluent in Kolkata and Ranaghat.

The microfibers generated from Polyester and Nylon based materials during washing cause serious environmental pollution by both contaminating the aquatic environment and the livelihood of the underwater creatures as well. This study aims at investigating the microfiber-pollution in wash effluents collected from different regions of Kolkata which is believed to be one of the microfiber-polluted cities in the South-east Asia in recent times. In this work, packed bed microfiltration (PBMF) was adopted in an economic and eco-friendly manner to arrest adequate amounts of microfibers and non-biodegradable matters present in the water samples collected from different regions of Kolkata and its surrounding areas. Moreover, effective parameters such as packed bed height to diameter ratio (H/D), mess size of the adopted filtration unit were varied from 0.71 to 2.85 and 60 to 100, respectively to understand the efficacy of the approach and to justify the potential of such alternative in order to alleviate the concern as well. The present study reveals that the microfiltration efficiency of the proposed PBMF unit was achieved maximum 93.5% for sample A and 92.2% for sample D respectively to reduce the microfiber count from 7614 to 543 in an hour operation at a flow rate of 60 L h-1. Besides, the cost of such system was found to be promising as much as 5 US$ on a yearly basis.

Immune responses in children after vaccination with a typhoid Vi-tetanus toxoid conjugate vaccine in Bangladesh.

A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection.

Appearance of tolerance-induction and non-inflammatory SARS-CoV-2 spike-specific IgG4 antibodies after COVID-19 booster vaccinations.

Background: Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants. Methods: A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years. Results: Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies. Conclusions: This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies.

Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.

BACKGROUND: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. METHODS: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. RESULTS: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. CONCLUSIONS: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.

Zinc sulphide nanoparticle (nZnS): A novel nano-modulator for plant growth.

In spite of extraordinary properties of zinc sulphide nanoparticle (nZnS), its role on plant system is not well understood, yet. Therefore, this study was aimed to assess the uptake, translocation and effects of nZnS in mung bean (Vigna radiata) plant at 0, 0.1, 0.5 and 1 mg L-1 concentrations. In this study, nZnS was synthesized by modified reflux method and physicochemical characterizations were conducted. The effects of nZnS on mung bean plant were determined by seed germination, growth parameters, membrane integrity and ROS-antioxidant defense assays. Our results showed that nZnS treatment has significantly increased seed germination, root-shoot length, pigment content and decreased lipid peroxidation. There were increased total antioxidant activity (TAA), DPPH and flavonoid contents found in treated plants. Also, nZnS treatment did not activate oxidative stress determined by SOD, CAT, CPX, APOX and GR activities. The uptake and translocation of nZnS in mung bean plants were determined by Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM), revelling that nZnS localized primarily in the vacuoles and chloroplasts. Besides, electron micrographs showed no alteration in cell structures between treated and control plants, further confirming that nZnS treatment has no phytotoxic effects. In vitro and in vivo studies on Zn release from nZnS were also determined using Inductively Coupled Plasma Mass Spectroscopy (ICPMS) and Energy Dispersive X-ray (EDX), which showed that the Zn release and particles uptake were concentration dependent. Overall, results of this study demonstrated the positive role of nZnS on growth and antioxidant defense responses in V. radiata at the experimental concentrations.

Feasibility, coverage and cost of oral cholera vaccination conducted by icddr,b using the existing national immunization service delivery mechanism in rural setting Keraniganj, Bangladesh.

Background: Cholera is a considerable health burden in developing country settings including Bangladesh. The oral cholera vaccine (OCV) is a preventative tool to control the disease. The objective of this study was to describe whether the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), could provide the OCV to rural communities using existing government infrastructure. Methods: The study was conducted in rural sub-district Keraniganj, 20 km from the capital city Dhaka. All listed participants one year and above in age (excluding pregnant women) were offered two doses of OCV at a 14 day interval. Existing government facilities were used to deliver and also maintain the cold chain required for the vaccine. All events related to vaccination were recorded at the 17 vaccination sites to evaluate the coverage and feasibility of OCV program. Results: A total of 29,029 individuals received the 1st dose (90% of target) and 26,611 individuals received the 2nd dose (83% of target and 92% of 1st dose individuals) of OCV. The highest vaccination coverage was in younger children (1-9 years) and the lowest was amongst 18-29-year age group. Somewhat better coverage was seen amongst the female participants than males (92% vs. 88% for the 1st dose and 93% vs. 90% for the 2nd dose). The cost of vaccine cost was calculated as US$1.00 per dose plus freight, insurance, and transportation and the total vaccine delivery cost was US$70,957. Conclusion: This was a project undertaken using existing public health program resources to collect empirical evidence on the use of a mass OCV campaign in the rural setting. Mass vaccination with the OCV is feasible in the rural setting using existing governmental vaccine delivery systems in Bangladesh.

Organization and implementation of an oral cholera vaccination campaign in an endemic urban setting in Dhaka, Bangladesh.

Bangladesh has historically been cholera endemic, with seasonal cholera outbreaks occurring each year. In collaboration with the government of Bangladesh, the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) initiated operational research to test strategies to reach the high-risk urban population with an affordable oral cholera vaccine (OCV) "ShancholTM" and examine its effectiveness in reducing diarrhea due to cholera. Here we report a sub-analysis focusing on the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. We described how the vaccination program was planned, prepared and implemented using different strategies to deliver oral cholera vaccine to a high-risk urban population in Dhaka, Bangladesh based on administrative data and observations made during the program. The objective of this study is to evaluate the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. OCV administration by trained local volunteers through outreach sites and mop-up activities yielded high coverage of 82% and 72% of 172,754 targeted individuals for the first and second dose respectively, using national Expanded Program on Immunization (EPI) campaign mechanisms without disrupting routine immunization activities. The cost of delivery was low. Safety and cold chain requirements were adequately managed. The adopted strategies were technically and programmatically feasible. Current evidence on implementation strategies in different settings together with available OCV stockpiles should encourage at-risk countries to use OCV along with other preventive and control measures.