Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.

BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

The Effect of Previous Exposure to Malaria Infection and Clinical Malaria Episodes on the Immune Response to the Two-Dose Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen.

We assessed whether the immunogenicity of the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen with a 56-day interval between doses was affected by exposure to malaria before dose 1 vaccination and by clinical episodes of malaria in the period immediately after dose 1 and after dose 2 vaccinations. Previous malaria exposure in participants in an Ebola vaccine trial in Sierra Leone (ClinicalTrials.gov: NCT02509494) was classified as low, intermediate, and high according to their antibody responses to a panel of Plasmodium falciparum antigens detected using a Luminex MAGPIX platform. Clinical malaria episodes after vaccinations were recorded as part of the trial safety monitoring. Binding antibody responses against the Ebola virus (EBOV) glycoprotein (GP) were measured 57 days post dose 1 and 21 days post dose 2 by ELISA and summarized as Geometric Mean Concentrations (GMCs). Geometric Mean Ratios (GMRs) were used to compare groups with different levels of exposure to malaria. Overall, 587 participants, comprising 188 (32%) adults (aged ≥ 18 years) and 399 (68%) children (aged 1-3, 4-11, and 12-17 years), were included in the analysis. There was no evidence that the anti-EBOV-GP antibody GMCs post dose 1 and post dose 2 differed between categories of previous malaria exposure. There was weak evidence that the GMC at 57 days post dose 1 was lower in participants who had had at least one episode of clinical malaria post dose 1 compared to participants with no diagnosed clinical malaria in the same period (GMR = 0.82, 95% CI: 0.69-0.98, p-value = 0.02). However, GMC post dose 2 was not reduced in participants who experienced clinical malaria post-dose 1 and/or post-dose 2 vaccinations. In conclusion, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in individuals with previous exposure to malaria and in those who experience clinical malaria after vaccination. This vaccine regimen is suitable for prophylaxis against Ebola virus disease in malaria-endemic regions.

Preference for utilitarian or hedonic value options during a pandemic crisis: The moderation effects of childhood socioeconomic status and sensation-seeking.

This research investigated hospitality consumers' relative preferences for utilitarian or hedonic value under COVID-19 pandemic conditions. A series of four experiments and one secondary data analysis showed that the salience of the infectious disease threat increased consumers' preferences for hospitality options that provide relatively more utilitarian than hedonic value. Additionally, we identified two individual differences (i.e., childhood socioeconomic status (SES) & sensation-seeking) that moderated the effect of the infectious disease threat on the preferred hospitality consumption value. Specifically, the higher the childhood SES, the higher was the preference for the utilitarian value option, and the lower the level of sensation-seeking, the greater was the preference for the utilitarian value option. This research extends our understanding of the influence of the infectious disease threat on preference changes in hospitality decisions.

Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial.

BACKGROUND: Children account for a substantial proportion of cases and deaths during Ebola virus disease outbreaks. We aimed to evaluate the safety and immunogenicity of a booster dose of the Ad26.ZEBOV vaccine in children who had been vaccinated with a two-dose regimen comprising Ad26.ZEBOV as dose one and MVA-BN-Filo as dose two. METHODS: We conducted an open-label, non-randomised, phase 2 trial at one clinic in Kambia Town, Sierra Leone. Healthy children, excluding pregnant or breastfeeding girls, who had received the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in a previous study, and were aged 1-11 years at the time of their first vaccine dose, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) and were followed up for 28 days. Primary outcomes were safety (measured by adverse events) and immunogenicity (measured by Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration) of the booster vaccine dose. Safety was assessed in all participants who received the booster vaccination; immunogenicity was assessed in all participants who received the booster vaccination, had at least one evaluable sample after the booster, and had no major protocol deviations that could have influenced the immune response. This trial is registered with ClinicalTrials.gov, NCT04711356. FINDINGS: Between July 8 and Aug 18, 2021, 58 children were assessed for eligibility and 50 (27 aged 4-7 years and 23 aged 9-15 years) were enrolled and received an Ad26.ZEBOV booster vaccination, more than 3 years after receiving dose one of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. The booster was well tolerated. The most common solicited local adverse event during the 7 days after vaccination was injection site pain, reported in 18 (36%, 95% CI 23-51) of 50 participants. The most common solicited systemic adverse event during the 7 days after vaccination was headache, reported in 11 (22%, 12-36) of 50 participants. Malaria was the most common unsolicited adverse event during the 28 days after vaccination, reported in 25 (50%, 36-64) of 50 participants. No serious adverse events were observed during the study period. 7 days after vaccination, the Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration was 28 561 ELISA units per mL (95% CI 20 255-40 272), which was 44 times higher than the geometric mean concentration before the booster dose. 21 days after vaccination, the geometric mean concentration reached 64 690 ELISA units per mL (95% CI 48 356-86 541), which was 101 times higher than the geometric mean concentration before the booster dose. INTERPRETATION: A booster dose of Ad26.ZEBOV in children who had received the two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen more than 3 years earlier was well tolerated and induced a rapid and robust increase in binding antibodies against Ebola virus. These findings could inform Ebola vaccination strategies in paediatric populations. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Head Injury Prevalence in a Population of Injured Patients Seeking Care in Ghana, West Africa.

Background/Significance: Much of the literature on head injury (HI) prevalence comes from high-income countries (HICs), despite the disproportionate burden of injuries in low to middle-income countries (LMICs). This study evaluated the HI prevalence in the Kintampo Injury Registry, a collaborative effort between Kintampo Health Research Centre (KHRC) in Ghana and the sidHARTe Program at Columbia University Mailman School of Public Health. In our first aim, we characterize the HI prevalence in the registry. In aim 2, we examine if there are any sex (male/female) differences in head injury outcomes in these populations for points of potential intervention. Methods: Secondary analysis of data from the Kintampo Injury Registry which had 7,148 registered patients collected during January 2013 to January 2015. The definition of a case was adopted to ensure consistency with the International Statistical Classification of Diseases and Related Health Problems, revision 10 (ICD-10). A 3-page questionnaire was used to collect data from injured patients to include in the registry. The questions were designed to be consistent with the World Health Organization (WHO) guidelines on injury surveillance and were adapted from the questionnaire used in a pilot, multi-country injury study undertaken in other parts of Africa. The questionnaire collected information on the anatomic site of injury (e.g., head), mechanism of injury (e.g., road traffic injuries, interpersonal injuries (including domestic violence), falls, drowning, etc.), severity and circumstances of the injury, as well as precipitating factors, such as alcohol and drug use. The questionnaire consisted mainly of close-ended questions and was designed for efficient data entry. For the secondary data analyses for this manuscript, we only included those with "1st visit following injury" and excluded all transfers and follow-up visits (n = 834). We then dichotomized the remaining 6,314 patients to head injured and non-head injured patients based on responses to the variable "Nature of injury =Head Injury". We used chi-square and Fisher's exact tests with p < 0.05 as cut-off for statistical significance. Logistic regression estimates were used for effect estimates. Results: Of the 6,314 patients, there were 208 (3.3%) head-injured patients and 6,106 (96.7%) patients without head injury. Head-injured patients tended to be older (Mean age: 28.9 +/-13.7; vs. 26.1 +/- 15.8; p = 0.004). Seven in 10 head injured patients sustained their injuries via transport/road traffic accidents, and head-injured patients had 13 times the odds of mortality compared with those without head injuries (OR: 13.3; 95% CI: 8.05, 22.0; p < 0.0001) even though over half of them had mild or moderate injury severity scores (p < 0.001). Evaluation of sex differences amongst the head-injured showed that in age-adjusted logistic regression models, males had 1.4 times greater odds of being head injured (OR: 1.4; 95% CI: 1.04, 2.00; p = 0.03) and over twice the risk of mortality (OR: 2.7; 95% CI: 0.74, 10.00; p = 0.13) compared to females. Conclusion: In these analyses, HI was associated with a higher risk of mortality, particularly amongst injured males; most of whom were injured in transport/road-traffic-related accidents. This study provides an impetus for shaping policy around head injury prevention in LMICs like Ghana.

Prevalence of malaria and helminth infections in rural communities in northern Sierra Leone, a baseline study to inform Ebola vaccine study protocols.

INTRODUCTION: Recurrent parasitic infections may influence the immune response to vaccines. In the Partnership for Research on Ebola VACcinations extended follow-UP and clinical research capacity build-UP (PREVAC-UP) study being undertaken in Mambolo, northern Sierra Leone, participants are being followed up to assess the potential impact of exposure to malaria and/or helminth infections on long-term immune response to two Ebola vaccines. To support the development of the assays that will be used in this evaluation, a parasitological survey was conducted in Mambolo between November 2019 and February 2020. METHODS: Healthy individuals aged ≥1 year who were resident in Mambolo Chiefdom were selected using a stratified sampling approach and questionnaires were administered to explore their sociodemographic characteristics. Microscopy was used to detect malaria parasites, intestinal helminths and urinary schistosome infections. Rapid blood tests were used to detect infections with Onchocerca volvulus and Wuchereria bancrofti. We estimated the overall prevalence of these infections and used adjusted logistic regression models to explore risk factors for malaria and hookworm infection. RESULTS: Eight hundred and fifteen (815) residents, 50.9% of whom were female were surveyed. Overall, 309 (39.1%) of 791 persons tested for malaria had a positive blood slide; Plasmodium falciparum was the dominant species. Helminth infection was detected in 122 (15.0%) of 815 stool samples including three mixed infections. The helminth infections comprised 102 (12.5%) cases of hookworm, 11 (1.3%) cases of Trichuris trichiura, 10 (1.2%) cases of Schistosoma mansoni and two (0.2%) cases of Ascaris lumbricoides. Being male (OR = 2.01, 95% CI 1.15-3.50) and residing in a non-riverine community (OR = 4.02, 95%CI 2.32-6.98) were the factors associated with hookworm infection. Onchocerca volvulus and Wuchereria bancrofti infections were found in 3.3% and 0.4% of participants respectively. CONCLUSION: Malaria and hookworm are the most prevalent parasite infections and those most likely to influence long-term immune response to Ebola vaccines among the trial participants.

Ebola Virus Glycoprotein IgG Seroprevalence in Community Previously Affected by Ebola, Sierra Leone.

We explored the association of Ebola virus antibody seropositivity and concentration with potential risk factors for infection. Among 1,282 adults and children from a community affected by the 2014-2016 Ebola outbreak in Sierra Leone, 8% were seropositive for virus antibodies but never experienced disease symptoms. Antibody concentration increased with age.

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial.

BACKGROUND: Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. METHODS: This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1-17 years were enrolled in three age cohorts (12-17 years, 4-11 years, and 1-3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. FINDINGS: From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1-3 years after placebo injection to 21% (30 of 144) of children aged 4-11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12-17 years and 4-11 years age cohorts after the first and second dose, and pyrexia in the 1-3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12-17 years (9929 ELISA units [EU]/mL [95% CI 8172-12 064]), in 119 (99%) of 120 aged 4-11 years (10 212 EU/mL [8419-12 388]), and in 118 (98%) of 121 aged 1-3 years (22 568 EU/mL [18 426-27 642]). INTERPRETATION: The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1-17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial.

BACKGROUND: The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. METHODS: The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1 × 108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant's last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. FINDINGS: Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736-6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312-4383]) at 21 days after the second vaccination. INTERPRETATION: The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

Determining the attributes that influence students' online learning satisfaction during COVID-19 pandemic.

The inevitable disruptions caused by COVID-19 in the hospitality and tourism education sector have made online learning a necessity rather than an option. This study employs the user experience questionnaire (UEQ) to examine students' online learning experiences specifically in the context of COVID-19. Data collection involved a Qualtrics online survey with a convenience sample of 216 tourism and hospitality students in Macau. Overall, results point to a generally positive appraisal of online attributes, but satisfaction is marginal. Initial principal component factor analysis generated three orthogonal factors of online learning attributes: "Perspicuity and dependability"; "Stimulation and attractiveness"; and "Usability and innovation". Further regression analysis reveals that "Stimulation and attractiveness" is the strongest predictor of the students' satisfaction regarding online learning during the COVID-19 disruptions. This novel finding points to the need for hospitality and tourism education institutions to develop an attractive and motivating visual environment for online course delivery since a stimulating online learning atmosphere is crucial in the context of the pedagogical disruptions caused by COVID-19. Nonetheless, these findings are specific to Chinese students and reflect their learning satisfaction which may differ in other contexts.

Correction: Exploring factors affecting quality implementation of lymphatic filariasis mass drug administration in Bole and Central Gonja Districts in Northern Ghana.

[This corrects the article DOI: 10.1371/journal.pntd.0007009.].

Evaluating context-specific evidence-based quality improvement intervention on lymphatic filariasis mass drug administration in Northern Ghana using the RE-AIM framework.

BACKGROUND: Over a decade of implementing a global strategy to eliminate lymphatic filariasis in Ghana through mass drug administration, the disease is still being transmitted in 11 districts out of an initial 98 endemic districts identified in 2000. A context-specific evidence-based quality improvement intervention was implemented in the Bole District of Northern Ghana after an initial needs assessment to improve the lymphatic filariasis mass drug administration towards eliminating the disease. Therefore, this study aimed to evaluate the process and impact of the lymphatic filariasis context-specific evidence-based quality improvement intervention in the Bole District of Northern Ghana. METHOD: A cross-sectional mixed methods study using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to evaluate the context-specific evidence-based quality improvement intervention was employed. Quantitative secondary data was extracted from the neglected tropical diseases database. A community survey was conducted with 446 randomly selected participants. Qualitative data were collected from 42 purposively selected health workers, chiefs/opinion leaders and community drug distributors in the study area. RESULTS: The evaluation findings showed an improvement in social mobilisation and sensitisation, knowledge about lymphatic filariasis and mass drug administration process, willingness to ingest the medication and adherence to the direct observation treatment strategy. We observed an increase in coverage ranging from 0.1 to 12.3% after implementing the intervention at the sub-district level and reducing self-reported adverse drug reaction. The level of reach, effectiveness and adoption at the district, sub-district and individual participants' level suggest that the context-specific evidence-based quality improvement intervention is feasible to implement in lymphatic filariasis hotspot districts based on initial context-specific needs assessment. CONCLUSION: The study provided the groundwork for future application of the RE-AIM framework to evaluate the implementation of context-specific evidence-based quality improvement intervention to improve lymphatic filariasis mass drug administration towards eliminating the disease as a public health problem.

Estimating causes of death where there is no medical certification: evolution and state of the art of verbal autopsy.

Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale.

Continuous positive airway pressure in managing acute respiratory distress in children in district hospitals: evidence for scale-up.

In children, acute respiratory distress (ARD) is a clinical presentation requiring emergency management, including mechanical ventilation. Mechanical ventilators are lacking in sub-Saharan Africa. Continuous Positive Airway Pressure (CPAP) is an alternative form of non-invasive respiratory support that has been used in high-income countries for over four decades. Its use in sub-Saharan Africa is, however, limited and often restricted to neonates. Controlled trials in Ghana have shown that the use of CPAP in children younger aged 1-12 months reduces 2-week all-cause mortality from ARD by 60% (RR 0·40, 0·19-0·82; p=0·01). The absolute reduction in mortality of 4% implies one infant life saved for every 25 children treated with CPAP. This paper reviews the findings of the trials in Ghana and contrasts the findings with those of trials in Bangladesh and Malawi. It makes the case that implementation research (rather than more controlled trials) is now needed to support the routine, safe and effective use of CPAP in managing ARD in older infants in district hospitals in Ghana. Funding: None declared.

Preference for robot service or human service in hotels? Impacts of the COVID-19 pandemic.

Robots and artificial intelligence (AI) technologies are becoming more prominent in the tourism industry. Nowadays, consumers are faced with multiple options involving both human and robot interactions. A series of experimental studies were implemented. Four experiments demonstrated that consumers had a more positive attitude toward robot-staffed (vs. human-staffed) hotels when COVID-19 was salient. The results were different from previous studies, which were conducted before the COVID-19 pandemic. Since the moderating role of perceived threat in consumers' preference for robot-staffed hotels was significant, the respondents' preference was attributed to the global health crisis. This research provides a number of theoretical and managerial implications by improving the understanding of technology acceptance during a health crisis.

Referral of sick children and levels of adherence by carers: implications on quality health care in the middle belt of Ghana.

Introduction: Severely sick-children presenting at primary healthcare facilities need referral to higher level facilities for better care. Adherence to referrals and quality of care received by those referred could serve as critical steps towards their survival. Objective: To describe experiences with severely sick children referred to higher-level health facilities for care and reasons for non-adherence to referral; to explore healthcare provider's perspectives to referral. Methods: Referrals among 3046 young children were followed for adherence. Assessment of children referred from a PHC facility adhering to referral advice and reasons for non-adherence to referral was determined. Agreement on reported diagnoses at PHC centres and health-facilities receiving patients was assessed. Perspectives of healthcare providers were assessed. Results: 212 children were referred from PHC centres to various hospitals with 14.2% non-adherence. Reasons given: 48.3% of carers adhering felt child's condition was severe; 43.3% complied with healthcare provider directive. The main reasons for non-adherence to referral were no money for transport (50%) and child condition not serious (30.0%). 69.0% of anaemia cases diagnosed at PHC facilities and hospitals. 65.7% fever diagnosed at a PHC centres were confirmed as malaria at the hospitals. Healthcare providers referred patients for severity, perceivedcomplication and non-response to treatment. Conclusion: Adherence was generally good. The level of agreement in diagnosis of common diseases such as malaria and anaemia at PHC centres and district hospitals was high and low for rarer diseases. Capacity should be provided at PHC levels for adequate management of cases presented to reduce referrals carers have to make. Funding: This study did not receive funding from any external sources.

Exploring factors affecting quality implementation of lymphatic filariasis mass drug administration in Bole and Central Gonja Districts in Northern Ghana.

Ghana has been implementing Mass Drug Administration (MDA) since the year 2001, and Lymphatic Filariasis transmission has been interrupted in 76 out of the 98 targeted districts. The remaining districts have a microfilaria prevalence above the 1% threshold needed for the interruption of transmission. This study assesses the level of lymphatic filariasis MDA coverage and explored factors affecting the quality of implementation of the MDA in the Bole and Central Gonja Districts of Northern Ghana. A concurrent mixed methods study design approach was used to provide both a quantitative and qualitative insight. A descriptive analysis was carried out, and the results are presented in tables and charts. The transcripts of the qualitative interviews were imported into Nvivo and framework methods of analysis were used. The results were summarized based on the themes and buttressed with narratives with key quotes presented within the texts. The overall MDA coverage in Central Gonja is 89.3% while that of Bole district is 82.9%. Refusal to ingest the drug and adverse drug reactions were higher in Bole district than the Central Gonja District. The persistent transmission of lymphatic filariasis in Bole District was characterized by poor community mobilization and sensitization, nonadherence to the directly observed treatment strategy, refusal to ingest the drug due to the fear of adverse drug reactions, inadequate knowledge and misconceptions about the disease. Reported mass drug administration coverage will not necessarily result into interruption of transmission of the disease without strict compliance to the directly observed treatment strategy, strong stakeholder engagement coupled with evidence-based context-specific multi-channel community education strategies with key educational messages on the cause of the disease and adverse drug reactions. While the clock for the elimination of lymphatic filariasis by the year 2020 and meeting of the Sustainable Development Goal 3 target 3.3 by 2030 is ticking, there is an urgent need for a concerted effort to improve the fidelity of the ongoing lymphatic filariasis MDA campaigns in the Bole District of Northern Ghana.

Making primary healthcare responsive to non-communicable diseases in sub-Saharan Africa.

Primary healthcare (PHC) meets the needs of people's health throughout their lives and empowers individuals and communities to oversee their own health. Most of the community-based activities currently undertaken in PHC in sub-Saharan Africa (SSA) address child and maternal health. Non-communicable diseases are now major causes of morbidity and premature mortality in SSA. In this paper, I propose the formal integration of community-based, non-communicable disease prevention and early detection into PHC activities. I offer practical suggestions on how this can be achieved to ensure a continuum of care.

Towards effective participation of the private health sector in Ghana's COVID-19 response.

The private health sector is a major service provider group within the health systems of most sub-Saharan African countries. Currently, 90% of COVID-19 cases in Ghana are in urban areas where private health facilities play a major role in service delivery. Yet, there is limited understanding of the issues mediating private health sector participation in public health emergency responses. Challenges related to its involvement in Ghana´s COVID-19 response include lack of clarity on its role, sub-optimal communication channels, inadequate personal protective equipment and fragmentation of the sector. Hence, operational and regulatory actions addressing these challenges will ensure the private sector is fully prepared to contribute to the COVID-19 response and future public health emergencies, thereby strengthening Ghana's health system.