•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.
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.
•We compared the vaccine effectiveness of bivalent and monovalent COVID-19 vaccines.•Bivalent COVID-19 vaccines offer significantly better protection.•It offered greater protection to long-term care ...facility residents.•Maximum additional protection was observed 3-4 months after vaccination.
To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data.
This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups.
We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval CI 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%).
Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.
The availability and use of vaccines for the coronavirus disease 2019 (COVID-19) in low and middle-income countries (L/MICs) lags far behind more affluent countries, and vaccines currently used in ...L/MICs are predominantly of lower efficacy. As vaccines continue to be rolled out in L/MICs, successful control of COVID-19 by vaccines requires monitoring both of vaccine protection of vaccinees (effectiveness) and of the entire targeted populations, including vaccine herd protection of non-vaccinees (impact). To be of greatest relevance to L/MICs, there is the need to address the distinctive medical and demographic features of populations, health systems, and demography that may greatly affect vaccine performance in these settings. We identified 58 published studies that included 85 evaluations of the effectiveness of different COVID-19 vaccines globally. Only three were done in L/MICs, and no impact studies were identified in these settings. Post-deployment studies of the protection by COVID-19 vaccines rolled out in L/MICs constitute an important but currently neglected global priority.
ObjectiveTo investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly ...endemic.Design, setting and participantsWe assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the ‘non-intervention’ clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area.Primary outcome measureFirst severe cholera episode detected during follow-up period.MethodsWe applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary (‘better’, ‘not better’) composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between ‘better’ WASH households and severe cholera risk over 4 years in the entire study population.ResultsThe ‘better’ WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of ‘better’ WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a ‘better’ WASH household and severe cholera persisted in all age groups.ConclusionsSalutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings.Trial registration numberThis article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.gov NCT01339845
Abstract
Background
Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using ...typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.
Methods
A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.
Results
The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval CI, 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001).
Conclusions
Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.
Clinical Trials Registration
ISRCTN11643110.
Better preexisting household water, sanitation, and hygiene and delivering Vi-TT vaccine act independently to reduce typhoid risk, so that the combination of both yields greater protection against typhoid at the population level (71%) than either vaccination (55%) or improved WASH alone (37%).
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.
•“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 inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine ...(mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV).
We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6–10–14 weeks/fIPV at 6 weeks (A); mOPV1 at 6–10–14 weeks/fIPV at 10 weeks (B); mOPV1 at 6–10–14 weeks (C); and bOPV at 6–10–14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004).
During 18 December 2018 – 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% 95% CI: 91–97%) versus two mOPV1 doses with fIPV at 6 weeks (96% 93–98%) or 10 weeks (96% 93–98%). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines.
Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV.
U.S. Centers for Disease Control and Prevention.
Typhoid fever, or enteric fever, is a highly fatal infectious disease that affects over 9 million people worldwide each year, resulting in more than 110,000 deaths. Reduction in the burden of typhoid ...in low-income countries is crucial for public health and requires the implementation of feasible water, sanitation, and hygiene (WASH) interventions, especially in densely populated urban slums.
In this study, conducted in Mirpur, Bangladesh, we aimed to assess the association between household WASH status and typhoid risk in a training subpopulation of a large prospective cohort (n=98,087), and to evaluate the performance of a machine learning algorithm in creating a composite WASH variable. Further, we investigated the protection associated with living in households with improved WASH facilities and in clusters with increasing prevalence of such facilities during a 2-year follow-up period.
We used a machine learning algorithm to create a dichotomous composite variable ("Better" and "Not Better") based on 3 WASH variables: private toilet facility, safe drinking water source, and presence of water filter. The algorithm was trained using data from the training subpopulation and then validated in a distinct subpopulation (n=65,286) to assess its sensitivity and specificity. Cox regression models were used to evaluate the protective effect of living in "Better" WASH households and in clusters with increasing levels of "Better" WASH prevalence.
We found that residence in households with improved WASH facilities was associated with a 38% reduction in typhoid risk (adjusted hazard ratio=0.62, 95% CI 0.49-0.78; P<.001). This reduction was particularly pronounced in individuals younger than 10 years at the first census participation, with an adjusted hazard ratio of 0.49 (95% CI 0.36-0.66; P<.001). Furthermore, we observed an inverse relationship between the prevalence of "Better" WASH facilities in clusters and the incidence of typhoid, although this association was not statistically significant in the multivariable model. Specifically, the adjusted hazard of typhoid decreased by 0.996 (95% CI 0.986-1.006) for each percent increase in the prevalence of "Better" WASH in the cluster (P=.39).
Our findings demonstrate that existing variations in household WASH are associated with differences in the risk of typhoid in densely populated urban slums. This suggests that attainable improvements in WASH facilities can contribute to enhanced typhoid control, especially in settings where major infrastructural improvements are challenging. These findings underscore the importance of implementing and promoting comprehensive WASH interventions in low-income countries as a means to reduce the burden of typhoid and improve public health outcomes in vulnerable populations.
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.
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