scholarly journals Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infection Among Bangladeshi Children: A Protocol for a Phase IIIb Trial

2019 ◽  
Vol 68 (Supplement_2) ◽  
pp. S74-S82 ◽  
Author(s):  
Katherine Theiss-Nyland ◽  
Firdausi Qadri ◽  
Rachel Colin-Jones ◽  
K Zaman ◽  
Farhana Khanam ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Conjugate Vaccine ◽  
Controlled Trial ◽  
Incidence Rates ◽  
World Health ◽  
Ethical Review ◽  
Research Review ◽  
Double Blind ◽  
Cluster Randomized ◽  
The Impact

AbstractBackgroundTyphoid fever illnesses are responsible for more than 100 000 deaths worldwide each year. In Bangladesh, typhoid fever is endemic, with incidence rates between 292–395 per 100 000 people annually. While considerable effort has been made to improve access to clean water and sanitation services in the country, there is still a significant annual typhoid burden, which particularly affects children. A typhoid conjugate vaccine (Vi-TCV) was recently prequalified by the World Health Organization and recommended for use, and offers the potential to greatly reduce the typhoid burden in Bangladesh.MethodsThis study is a double-blind, cluster-randomized, controlled trial of Vi-TCV in a geographically defined area in Dhaka, Bangladesh. At least 32 500 children from 9 months to <16 years of age will be vaccinated and followed for 2 years to assess the effectiveness and safety of Vi-TCV in a real-world setting. All cluster residents will also be followed to measure the indirect effect of Vi-TCV in this community.Ethics and DisseminationThis protocol has been approved by the International Centre for Diarrhoeal Disease Research, Bangladesh; a University of Oxford research review; and both ethical review committees. Informed written consent and assent will be obtained before enrollment. Vi-TCV has been shown to be safe and effective in previous, smaller-scale studies. The results of this study will be shared through a series of peer-reviewed journal articles. The findings will also be disseminated to the local government, stakeholders within the community, and the population within which the study was conducted.ConclusionsThis trial is the largest and only cluster-randomized control trial of Vi-TCV ever conducted, and will describe the effectiveness of Vi-TCV in an endemic population. The results of this trial may provide important evidence to support the introduction of TCVs in countries with a high burden of typhoid.Clinical Trials RegistrationISRCTN11643110.

scholarly journals Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 281
Author(s):  
Andrea Haekyung Haselbeck ◽  
Birkneh Tilahun Tadesse ◽  
Juyeon Park ◽  
Malick M. Gibani ◽  
Ligia María Cruz Espinoza ◽  
...  
Keyword(s):  
Public Health ◽  
Blood Culture ◽  
Typhoid Fever ◽  
Conjugate Vaccine ◽  
Incidence Rates ◽  
Health Programs ◽  
Public Health Programs ◽  
High Burden ◽  
Pan African ◽  
Cluster Randomized

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

scholarly journals Extended effect of short-course azithromycin for the treatment of diarrhoea in children on antimicrobial resistance in nasopharyngeal and intestinal bacteria: Study Protocol for the antimicrobial resistance sub-study of the multicountry AntiBiotics for Children with Diarrhea (ABCD) trial.

2020 ◽  
Author(s):  
T Alam ◽  
D Ahmed ◽  
T Ahmed ◽  
MJ Chisti ◽  
MW Rahman ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Low Income ◽  
Fecal Sample ◽  
World Health ◽  
Ethical Review ◽  
Controlled Clinical Trial ◽  
Small Subset ◽  
Double Blind ◽  
Severe Stunting ◽  
The Impact

Antimicrobial resistance (AMR) is a major public health challenge worldwide, threatening the important gains that have been made in reducing mortality due to infectious diseases. Despite current World Health Organization guidelines restricting antibiotics to a small subset of children with dysentery or suspected cholera, many children with diarrhea continue to be treated with antibiotics. We aim to determine the impact of a 3-day course of azithromycin on the risk of AMR at 90 and 180 days after treatment, among a subset of children and their household contacts enrolled into a multi-country, randomized, double-blind, placebo-controlled clinical trial of azithromycin children under 2 years with diarrhea in low income settings, Methods and analysis The AntiBiotics for Children with Diarrhea (ABCD) trial is testing the efficacy of a 3-day course of azithromycin, compared to placebo, in reducing mortality and linear growth faltering in the subsequent 6 months among 11,500 children aged 2-23 months of age across multiple sites in Bangladesh, India, Kenya Malawi, Mali, Pakistan and Tanzania with diarrhea and one or more of the following; dehydration, severe stunting, or moderate wasting (https://clinicaltrials.gov/ct2/show/NCT03130114). A sub-set of enrolled children are randomly selected to participate in a sub-study of AMR. A fecal sample (stool or rectal swab) will be collected at baseline from all enrolled children. A fecal sample and a nasopharyngeal (NP) swab will be collected at day 90 and 180 after enrolment from participating children and a close household child contact. Escherichia coli and Streptococcus pneumoniae will be isolated and Minimum Inhibitory Concentration for azithromycin and other commonly used antibiotics will be determined and compared between trial arms. Ethics and dissemination This study was reviewed by an independent ethical review committee. Dissemination of results is planned to local and international policy makers and the public.

scholarly journals Multi-Micronutrient Fortified Rice Improved Serum Zinc and Folate Concentrations of Cambodian School Children. A Double-Blinded Cluster-Randomized Controlled Trial

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2843
Author(s):  
Khov Kuong ◽  
Pety Tor ◽  
Marlene Perignon ◽  
Marion Fiorentino ◽  
Chhoun Chamnan ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Serum Zinc ◽  
Vulnerable Groups ◽  
Serum Folate ◽  
Micronutrient Deficiencies ◽  
Double Blind ◽  
Micronutrient Status ◽  
Zinc Concentrations ◽  
Cluster Randomized ◽  
The Impact

Background: Within Cambodia, micronutrient deficiencies continue to be prevalent in vulnerable groups, such as women and children. Fortification of staple foods such as rice could be a promising strategy for Cambodia to improve micronutrient status. Objective: Our objective was to investigate the impact of multiple-micronutrient fortified rice (MMFR), distributed through a World Food Program school-meals program (WFP-SMP) on serum zinc concentrations and folate status in a double-blind, cluster-randomized, placebo-controlled trial. Methods: Sixteen schools were randomly assigned to receive one of three different types of extruded-fortified rice (UltraRice Original (URO), UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. A total of 1950 schoolchildren (6–16 years old) participated in the study. Serum zinc (all groups) and folate (only in NutriRice and placebo group) concentrations were assessed from morning non-fasting antecubital blood samples and were measured at three time points (baseline and after three and six months). Results: After six months of intervention, serum zinc concentrations were significantly increased in all fortified rice group compared to placebo and baseline (0.98, 0.85 and 1.40 µmol/L for URO, URN and NutriRice, respectively) (interaction effect: p < 0.001 for all). Children in the intervention groups had a risk of zinc deficiencies of around one third (0.35, 039, and 0.28 for URO, URN, and NutriRice, respectively) compared to the placebo (p < 0.001 for all). The children receiving NutriRice had higher serum folate concentrations at endline compared to children receiving normal rice (+2.25 ng/mL, p = 0.007). Conclusions: This study showed that the high prevalence of zinc and folate deficiency in Cambodia can be improved through the provision of MMFR. As rice is the staple diet for Cambodia, MMFR should be considered to be included in the school meal program and possibilities should be explored to introduce MMFR to the general population.

scholarly journals Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Joseph M. Wagman ◽  
Kenyssony Varela ◽  
Rose Zulliger ◽  
Abuchahama Saifodine ◽  
Rodaly Muthoni ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Indoor Residual Spraying ◽  
Malaria Vectors ◽  
Light Traps ◽  
High Burden ◽  
Randomized Controlled ◽  
Pirimiphos Methyl ◽  
Cluster Randomized ◽  
The Impact ◽  
Long Lasting Insecticidal Nets

Abstract Background The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. Methods The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October–November 2016 and again in October–November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. Results The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33–59%; p < 0.001) in indoor light traps and by 74% (CI95 38–90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00–1.21) in no-IRS villages and 0.88 (CI95 0.67–1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47–88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22–87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7–53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. Conclusion IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia—a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registrationclinicaltrials.gov, NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

scholarly journals Frequency of repositioning for preventing pressure ulcers in patients hospitalized in ICU: protocol of a cluster randomized controlled trial

BMC Nursing ◽  
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Olga L. Cortés ◽  
Mauricio Herrera-Galindo ◽  
Juan Carlos Villar ◽  
Yudi A. Rojas ◽  
María del Pilar Paipa ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Critical Care ◽  
Pressure Ulcers ◽  
Controlled Trial ◽  
Cluster Randomized Controlled Trial ◽  
Control Group ◽  
Randomized Controlled ◽  
Link Type ◽  
Cluster Randomized ◽  
The Impact

Abstract Background Despite being considered preventable, ulcers due to pressure affect between 30 and 50% of patients at high and very high risk and susceptibility, especially those hospitalized under critical care. Despite a lack of evidence over the efficacy in prevention against ulcers due to pressure, hourly repositioning in critical care as an intervention is used with more or less frequency to alleviate pressure on patients’ tissues. This brings up the objective of our study, which is to evaluate the efficacy in prevention of ulcers due to pressure acquired during hospitalization, specifically regarding two frequency levels of repositioning or manual posture switching in adults hospitalized in different intensive care units in different Colombian hospitals. Methods A nurse-applied cluster randomized controlled trial of parallel groups (two branches), in which 22 eligible ICUs (each consisting of 150 patients), will be randomized to a high-frequency level repositioning intervention or to a conventional care (control group). Patients will be followed until their exit from each cluster. The primary result of this study is originated by regarding pressure ulcers using clusters (number of first ulcers per patient, at the early stage of progression, first one acquired after admission for 1000 days). The secondary results include evaluating the risk index on the patients’ level (Hazard ratio, 95% IC) and a description of repositioning complications. Two interim analyses will be performed through the course of this study. A statistical difference between the groups < 0.05 in the main outcome, the progression of ulcers due to pressure (best or worst outcome in the experimental group), will determine whether the study should be put to a halt/determine the termination of the study. Conclusion This study is innovative in its use of clusters to advance knowledge of the impact of repositioning as a prevention strategy against the appearance of ulcers caused by pressure in critical care patients. The resulting recommendations of this study can be used for future clinical practice guidelines in prevention and safety for patients at risk. Trial registration PENFUP phase-2 was Registered in Clinicaltrials.gov (NCT04604665) in October 2020.

scholarly journals Community intervention for child tuberculosis active contact investigation and management: study protocol for a parallel cluster randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anca Vasiliu ◽  
Sabrina Eymard-Duvernay ◽  
Boris Tchounga ◽  
Daniel Atwine ◽  
Elisabete de Carvalho ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Standard Of Care ◽  
Preventive Therapy ◽  
Community Based ◽  
Randomized Controlled ◽  
Eligible Child ◽  
Contact Investigation ◽  
Cluster Randomized ◽  
The Impact ◽  
Index Cases

Abstract Background There are major gaps in the management of pediatric tuberculosis (TB) contact investigation for rapid identification of active tuberculosis and initiation of preventive therapy. This study aims to evaluate the impact of a community-based intervention as compared to facility-based model for the management of children in contact with bacteriologically confirmed pulmonary TB adults in low-resource high-burden settings. Methods/design This multicenter parallel open-label cluster randomized controlled trial is composed of three phases: I, baseline phase in which retrospective data are collected, quality of data recording in facility registers is checked, and expected acceptability and feasibility of the intervention is assessed; II, intervention phase with enrolment of index cases and contact cases in either facility- or community-based models; and III, explanatory phase including endpoint data analysis, cost-effectiveness analysis, and post-intervention acceptability assessment by healthcare providers and beneficiaries. The study uses both quantitative and qualitative analysis methods. The community-based intervention includes identification and screening of all household contacts, referral of contacts with TB-suggestive symptoms to the facility for investigation, and household initiation of preventive therapy with follow-up of eligible child contacts by community healthcare workers, i.e., all young (< 5 years) child contacts or older (5–14 years) child contacts living with HIV, and with no evidence of TB disease. Twenty clusters representing TB diagnostic and treatment facilities with their catchment areas are randomized in a 1:1 ratio to either the community-based intervention arm or the facility-based standard of care arm in Cameroon and Uganda. Randomization was stratified by country and constrained on the number of index cases per cluster. The primary endpoint is the proportion of eligible child contacts who initiate and complete the preventive therapy. The sample size is of 1500 child contacts to identify a 10% difference between the arms with the assumption that 60% of children will complete the preventive therapy in the standard of care arm. Discussion This study will provide evidence of the impact of a community-based intervention on household child contact screening and management of TB preventive therapy in order to improve care and prevention of childhood TB in low-resource high-burden settings. Trial registration ClinicalTrials.gov NCT03832023. Registered on 6 February 2019

scholarly journals Azithromycin Reduction to Reach Elimination of Trachoma (ARRET): study protocol for a cluster randomized trial of stopping mass azithromycin distribution for trachoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abdou Amza ◽  
Boubacar Kadri ◽  
Beido Nassirou ◽  
Ahmed M. Arzika ◽  
Ariana Austin ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Controlled Trial ◽  
Clinical Signs ◽  
Cluster Randomized Trial ◽  
World Health ◽  
Baseline Assessment ◽  
Randomized Controlled ◽  
Registration Number ◽  
Cluster Randomized ◽  
Health Organization

Abstract Background The World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation—follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines. Methods The Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission. Discussion The results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. Trial registration number This study is registered at clinicaltrials.gov (NCT04185402). Registered December 4, 2019; prospectively registered pre-results.

scholarly journals Impact of Spirulina corn soy blend on Iron deficient children aged 6–23 months in Ndhiwa Sub-County Kenya: a randomized controlled trial

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dorothy Apondi Othoo ◽  
Sophie Ochola ◽  
Elizabeth Kuria ◽  
Judith Kimiywe
Keyword(s):  
Controlled Trial ◽  
Study Groups ◽  
World Health ◽  
Deficiency Anemia ◽  
Group Assignment ◽  
Large Numbers ◽  
Blood Drawing ◽  
Iron Deficient ◽  
Risk Magnitude ◽  
The Impact

Abstract Background Iron deficiency anemia (IDA) remains high in Kenya despite interventions. Twenty-seven percent of children aged 6 months-14 years are anemic, with low iron intake (7%) among children aged 6–23 months. Standard food interventions involve a corn soy blend (CSB), which is limited in micronutrients, and fortifiers are not accessible locally. Moreover, the use of spirulina as a strategy for mitigating IDA has not been adequately documented. This study compared the impact of a spirulina corn soy blend (SCSB) on IDA among children aged 6–23 months. Methods A total of 240 children with IDA were randomly assigned to study groups at a ratio of 1:1:1 through lotteries, and caregivers and research assistants were blinded to group assignment. Dry-take-home SCSB, CSB and placebo flour (1.7 kg) was given to caregivers to prepare porridges using a flour water ratio of 1:4, producing 600 ml–700 ml of porridge to feed children 200 ml of porridge three times a day for 6 months. Impact was assessed as plasma hematocrit at baseline and after the study. Blood drawing, preparation and analysis were performed in accordance with approved procedures by the EthicsResearchCommittee. Monthly follow-up and data collection on dietary intake, anthropometry, morbidity and infant feeding practices were performed using questionnaires. Relative risk, magnitude of change and log-rank tests were used to compare the impact of the intervention, and significant differences were determined at P < 0.05. Results The survival probabilities for children consuming SCSB were significantly higher than those consuming CSB (log-rank-X2 = 0.978; CI: 0.954–1.033, P = 0.001) and the placebo (log-rankX2 = 0.971; CI: 0.943–0.984, P = 0.0001). Children consuming SCSB had a mean recovery time of 8 days (CI: 7–12 days) compared to those consuming CSB (19 days; CI: 20–23 days) and placebo (33 days; CI: 3 1–35 days). The recovery rate was 15.4 per 100 persons per day for children who consumed SCSB as opposed to 4.6 and 1.8 per 100 persons per day for those who consumed CSB and the placebo, respectively. Conclusion Management of IDA with SCSB compared to CSB and the placebo led to faster reversal and large numbers of recoveries from IDA. The recovery rates were above the World Health Organizations (WHO) minimums standards for food interventions. Efforts to realize high and faster recoveries from IDA should be heightened by fortifying CSB with spirulina powder.

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