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HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV. Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh

BACKGROUND: After global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. METHODS: We conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (

An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients.SPECTRA participants at eight study sites in the Philippines who developed rRT-PCR-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for three weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections.154 eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: 0.15-3.90) if the index case was a SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28-97). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97). Impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76-100) was measurable but the low numbers undermine the clinical significance.In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether index cases were symptomatic or not.

Background Rotavirus is one of the causes of severe diarrhea and death in young children. To control the disease, safe and effective vaccines are being used in several countries. We assessed the impact of vaccination on the risk factors for acute rotavirus diarrhea (ARD) in Bangladesh. Methods We used the data of a cluster-randomized trial. The clusters were 142 villages, 71 in each of the two arms of study. The infants were offered human rotavirus vaccine (HRV), Rotarix, over three-year period. We divided the time period into two equal periods (T1 and T2). A generalized estimating equation with logit-link function was used to evaluate the risk factors by arm and by period. Results Among 10,917 children, 5,759 (53%) were in the HRV villages. We had 359 cases; 44% in the HRV villages. Mean age of attack was similar between the arms of study in T1, but significantly higher in HRV villages than that in the non-HRV villages in T2. In HRV villages, males were at a higher risk of having ARD than females in T1, but not in T2. In contrast, males were at a higher risk of having ARD in both the time periods in non-HRV villages. In HRV-villages, children having literate mother were at significantly higher risk of having ARD in T1 but not in T2; whereas children in the non-HRV villages had a higher risk of having ARD in T2. Children living in an area with higher phone users had more cases than their counterpart in non-HRV villages, but not in HRV villages. Conclusion Our study illustrates that several risk factors for ARD varied between the two arms of study as well as between the two periods of study. Assessing post-vaccination risk factors is, therefore, important for understanding the impact of vaccination and undertaking post-vaccination control measures.

Chronic diseases, including non-communicable diseases (NCDs), have arisen as a severe threat to health and socio-economic growth. Telemedicine can provide both the highest level of patient satisfaction and the lowest risk of infection during a pandemic. The factors associated with its usage and patient adherence are not visible in Bangladesh’s resource-constrained settings. Therefore, this study aimed to identify perceptions about telemedicine among populations with chronic diseases amid the COVID-19 pandemic. A closed-ended self-reported questionnaire was created, and the questionnaire was written, reviewed, and finalized by a public health investigator, a psychiatrist, and an epidemiologist. The data for this study were collected from individuals using simple random sampling and snowball sampling techniques. Ethics approval was granted, and written/verbal consent was taken before interviews. Most of the participants showed a positive attitude towards telemedicine. People aged 35–54 years old and a higher level of education were less frequently associated with willingness to receive telemedicine services for current chronic disease (WRTCCD) than their counterparts. People living in urban areas and lower-income participants were more strongly associated with WRTCCD. Additionally, people who did not lose their earnings due to the pandemic were less strongly associated with WRTCCD. However, the main strength of this research is that it is a broad exploration of patient interest in several general forms of telehealth. In Bangladesh, there are many opportunities for telemedicine to be integrated into the existing healthcare system, if appropriate training and education are provided for healthcare professionals.

Modest improvements in household water, sanitation, and hygiene (WASH) and typhoid vaccination can reduce typhoid risk in endemic settings. However, empiric evaluation of their combined impact is lacking. A total of 62,756 persons residing in 80 clusters in a Kolkata slum were allocated randomly 1:1 to either the typhoid Vi polysaccharide (ViPS) vaccine or hepatitis A (Hep A) vaccine. Surveillance was conducted for 2 years before and 2 years after vaccination. We classified households as having “better” or “not better” WASH, and calculated the prevalence of better WASH households in clusters using previously validated criteria. We evaluated the protection by better household WASH, better household WASH prevalence, and ViPS vaccination against typhoid in all cluster members present at baseline using Cox proportional hazard models. Overall, ViPS vaccination was associated with a 55% (P P = 0.16; 95% CI, –16 to 59) overall. The reduction was 48% (P = 0.05; 95% CI, –1 to 73) in Hep A clusters, 6% (P = 0.85; 95% CI, –82 to 51) in ViPS clusters, and 57% (P

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.

Highlights • The “fried-egg” analytic approach was applied to a cluster randomized trial (CRT). • Overall analysis failed to reveal rotavirus vaccine (RV) herd protection. • Same approach unmasked herd protection of other enteric vaccines failed for RV., Background Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a ‘fried-egg’ approach whereby the analysis, restricted to the innermost households of clusters, ‘yolk’, creates an insulating ‘egg-white’ periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis. Methods In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively. Results During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size. Conclusion Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study.

Highlights • 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 treated patients. • Remission of fever, cough and sore throat did not differ between those treated with or without ivermectin. No severe adverse event observed with the longer duration of ivermectin use. • Larger trials will be needed to confirm these preliminary findings., Ivermectin, an FDA-approved anti-parasitic agent, was found in vitro to inhibit SARS-CoV-2 replication. To determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients we conducted a randomized, double-blind, placebo-controlled trial of oral ivermectin alone (12 mg once daily for 5 days) or in combination with doxycycline (12 mg ivermectin single dose and 200 mg stat doxycycline day-1 followed by 100 mg 12hrly for next 4 days) compared with placebo among 72 hospitalized patients in Dhaka, Bangladesh. Clinical symptoms of fever, cough and sore throat were comparable among the three treatment arms. Virological clearance was earlier in the 5-day ivermectin treatment arm versus the placebo group (9.7 days vs. 12.7 days; P = 0.02); but not with 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 mild COVID-19 adult patients. Larger trials will be needed to confirm these preliminary findings.

Low and middle income countries (LMICs) face many challenges in controlling COVID-19 in their countries. Health-care resources are limited and so are ICU beds. RT-PCR testing is conducted on a limited scale and treatment options are few. There is no vaccine. Therefore, what low cost solutions remain for the prevention, diagnosis, and treatment of SARS-CoV-2? How should these essential health services be delivered in order to reach the most vulnerable in our societies? In this editorial we discuss several important strategies for controlling COVID-19 including: vaccination, molecular and serological diagnostics, hygiene and WaSH interventions, and low-cost therapeutics. We also discuss the delivery of such services in order to reach the most in need. The proposed integrated control strategy requires immediate action and political will in order to reduce the widening health inequalities caused by the pandemic.

Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. cVDPV2 outbreaks are controlled with mass Sabin 2 OPV vaccination campaigns, which carry a small but serious risk of seeding future cVDPV2 outbreaks. Accurate forecasting models are essential for quantifying current and future cVDPV2 outbreak risk following Sabin 2 OPV campaigns, but it is unclear whether household community structure influences vaccine virus transmission or is relevant for assessing cVDPV2 outbreak risk. Here, we developed an agent-based model of Sabin 2 vaccine transmission to assess the role of household community structure on vaccine virus transmission following a mass OPV campaign performed in Matlab, Bangladesh. Household community structure strongly limits vaccine virus transmission to local community members and ignoring it overestimates outbreak risk in terms of emergence probability, duration, and epidemic size.

The non-specific beneficial effects of Bacille Calmette-Guérin (BCG) vaccination suggest that this vaccine might play a role in protecting individuals against severe coronavirus disease 2019 (COVID-19). Several studies propose that BCG vaccination may increase the body's immunity, thereby preventing respiratory infections caused by other respiratory pathogens. As the number of deaths due to COVID-19 is increasing rapidly and there is no specific treatment available to date, scientists are evaluating the effectiveness of already approved drugs as therapies against COVID-19, and the results were found to vary widely: from no significant effect being observed to a reduction in the time taken for clinical improvement. This study thus aims to evaluate whether it is worth performing clinical trials to examine the effects of the BCG vaccine on COVID-19. We herein emphasize the need to conduct phase III randomized controlled trials with adequate sample size and quality to investigate the effects of the BCG vaccine on COVID-19. In the event that BCG vaccination provides non-specific protection against COVID-19, administering it could be helpful in controlling the transmission of COVID-19 and other infectious diseases during future pandemics., Highlights • “Trained Immunity” is developed by BCG vaccination. • Heterologous T helper cell immune responses produced by BCG, remain elevated even 1-year post-vaccination. • BCG vaccination has non-specific effects against other respiratory infections. • BCG vaccine may provide non-specific protection in response to COVID-19. • More RCTs with adequate sample size and quality are warranted to investigate the BCG's effect on COVID-19

To support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants.In this phase III, mono-center, observer-blind study in Bangladesh, 6-10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV]2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated.Of 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, ≥97.9% of infants in each group had antibody concentrations ≥0.2 μg/mL; for 19A ≥ 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations.Immunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries. Clinical Trial Registry: NCT02447432.

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