Impact of educational intervention on knowledge and awareness of TB among secondary school students in The Gambia

Objectives: Health education and awareness campaigns about tuberculosis (TB) can empower adolescents on different aspects of the disease and its management, resulting in early and appropriate care seeking behavior through their advocacy in the community. We assessed the impact of educational intervention on knowledge and awareness about TB among adolescents in the greater Banjul area of The Gambia where approximately 70% of national TB cases are notified.Materials and Methods: A school-based, interventional analytical study, and interactive educational workshop was conducted among grade 12 students of the Methodist Academy Secondary School in Bakau, Banjul The Gambia. The workshop activities included illustrative demonstrations using posters, flipcharts, infographics, and games to convey TB messages in six domains: (1) Basic knowledge; (2) symptoms; (3) risk factors (4) modes of transmission; (5) treatment; and (6) care and support. Structured questionnaires were used to assess changes in the student’s knowledge and awareness about TB in the six domains before and after the workshop. Data were analyzed using proportional percentages, mean (95% CI) and differences standard error (SE) and student paired t-test.Results: Ninety-six students participated in the workshop out of which 92 (96%) students completed both pre- and post-test questionnaires. Sixty-eight percent of the students were females and 58% were from the science stream of the grade 12 students who participated in our workshop. The mean difference and SE between the pre- and post-workshop test scores in the six domains were: basic knowledge: +1.4 (0.2; P < 0.0001); symptoms: +1.5 (0.2; P < 0.0001); risk factors: +3.1 (0.3; P < 0.0001); modes of transmission: +1.2 (0.2; P < 0.0001); treatment: +0.8 (0.1; P < 0.0001); and care and support of TB: +0.5 (0.1; P = 0.0001).Conclusion: This school-based educational interactive workshop significantly improved the knowledge and awareness of the students especially in understanding the causative agent and risk factors of TB disease. We recommend exposure of students to TB educational activities as part of the school curriculum. The knowledge acquired in this workshop is likely to have impact on the wider community and should be assessed in future follow-up studies to determine if it impacts positively on views held within the wider community

Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689

Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022

BackgroundSeroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.MethodsWe obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG).ResultsA total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0–0.06] in March 2020 to a high of 89.4% [95% CI 83.36–93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06–62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83–40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence.ConclusionAnti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data

Complexos de ruteni amb lligands P-,N-donadors: Aplicació en catàlisi

En aquesta tesi doctoral s’han preparat una sèrie de complexos de ruteni(II) amb lligands heterobidentats P-,N-donadors i s’ha estudiat la seva activitat catalítica en les reaccions de transferència d’hidrogen per a la reducció de cetones amb isopropanol i l’alquilació d’amines amb alcohols. Els lligands sintetitzats són del tipus fosfinoamina, aminofosfinoimida i fosfinoimida. Aquests formen enllaços quelats de cinc o sis baules, depenent del seu esquelet, amb l’ió Ru(II). Els complexos sintetitzats són bàsicament de dos tipus: una família conté, a banda del lligand P-,N-donador, un lligand ƞ5-ciclopentadienil i una PPh3 o un lligand cloro; l’altre família de complexos, de geometria octaèdrica, conté dos lligands P-,Ndonadors i dos cloro que completen l’estructura. Tots aquests complexos presenten activitat catalítica en les reaccions de transferència d’hidrogen amb isopropanol per a la reducció de diferents cetones aromàtiques i alifàtiques. Els complexos també han demostrat ser actius per l’alquilació d’amines alifàtiques i aromàtiques amb diferents alcohols.In this PhD thesis a series of ruthenium (II) complexes with P-,N-donor ligands has been prepared. The catalytic activity of these complexes has been studied in hydrogen transfer reactions with isopropanol for reduction of ketones and the alkylation of amines with alcohols has been shown. The ligands synthetized are of phosphineamine, aminephosphineimide and phosphinoimide type. They form five and six membered chelated rings with the Ru(II) ion, depending on its backbone. The complexes synthesized are of two types: one family contains, in addition to the P-,N-donor ligand, one ƞ5-cyclopentadienyl and one PPh3 or chloro ligand; the other family of complexes contains two P-,N-donor ligands and two additional chloro to complete the octahedral geometry. All these complexes are active in hydrogen transfer reactions with isopropanol for the reduction of various aliphatic and aromatic ketones. The complexes also show activity for the alkylation of aromatic and aliphatic amines with different alcohols

Complexos de ruteni amb lligands P-,N-donadors: Aplicació en catàlisi

En aquesta tesi doctoral s'han preparat una sèrie de complexos de ruteni(II) amb lligands heterobidentats P-,N-donadors i s'ha estudiat la seva activitat catalítica en les reaccions de transferència d'hidrogen per a la reducció de cetones amb isopropanol i l'alquilació d'amines amb alcohols. Els lligands sintetitzats són del tipus fosfinoamina, aminofosfinoimida i fosfinoimida. Aquests formen enllaços quelats de cinc o sis baules, depenent del seu esquelet, amb l'ió Ru(II). Els complexos sintetitzats són bàsicament de dos tipus: una família conté, a banda del lligand P-,N-donador, un lligand ƞ5-ciclopentadienil i una PPh3 o un lligand cloro; l'altre família de complexos, de geometria octaèdrica, conté dos lligands P-,Ndonadors i dos cloro que completen l'estructura. Tots aquests complexos presenten activitat catalítica en les reaccions de transferència d'hidrogen amb isopropanol per a la reducció de diferents cetones aromàtiques i alifàtiques. Els complexos també han demostrat ser actius per l'alquilació d'amines alifàtiques i aromàtiques amb diferents alcohols.In this PhD thesis a series of ruthenium (II) complexes with P-,N-donor ligands has been prepared. The catalytic activity of these complexes has been studied in hydrogen transfer reactions with isopropanol for reduction of ketones and the alkylation of amines with alcohols has been shown. The ligands synthetized are of phosphineamine, aminephosphineimide and phosphinoimide type. They form five and six membered chelated rings with the Ru(II) ion, depending on its backbone. The complexes synthesized are of two types: one family contains, in addition to the P-,N-donor ligand, one ƞ5-cyclopentadienyl and one PPh3 or chloro ligand; the other family of complexes contains two P-,N-donor ligands and two additional chloro to complete the octahedral geometry. All these complexes are active in hydrogen transfer reactions with isopropanol for the reduction of various aliphatic and aromatic ketones. The complexes also show activity for the alkylation of aromatic and aliphatic amines with different alcohols

Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients

Abstract Background As a result of the lack of screening programs and the difficulty in making a proper diagnosis, the majority of hepatocellular carcinoma (HHC) patients present late in low-resource countries. The study therefore assesses the clinical features, stage and prognostic variables of patients with HCC in The Gambia. Methods From December 2015 to January 2019, patients with a confirmed diagnosis of HCC were enrolled. All patients’ medical history, ultrasound scan, FibroScan and laboratory details were collected. Results Two hundred and sixty (260) patients were enrolled. The mean age of HCC patients was 40 years, and 210 (80.7%) of them were male. The most common gastrointestinal symptoms were early satiety 229 (88.1%) and abdominal pain 288 (87.7%), while the most common constitutional symptoms were weight loss 237 (91.2%) and easy fatiguability 237 (91.2%). Hepatomegaly 205 (78.8%) was the most common sign. On ultrasound scan, lesions were mostly multifocal 175 (67.3%), and the median FibroScan score was 75 kPa. The median fibrosis 4 and aspartate transferase platelet ratio index were 4.6 and 2.2, respectively. Hepatitis B surface antigen (HBsAg) was positive in 170 (65.4%) patients, and the median AFP level was 3263 ng/ml. HCC patients with positive HBsAg were more likely to be male 145 (85.3%) vs 62 (72.1%) (p = 0.011), much younger 39.9 vs 51.4 yrs (p =  < 0.0001), more likely to have abdominal pain 156 (91.8%) vs 68 (79.1%) (p = 0.002), jaundice 78 (45.9%) vs 29 (33.7%) (p = 0.042), dark urine 117 (68.8%) vs 46 (53.5%) (p = 0.018), raised transaminases (Aspartate transaminases 224.5 (32–7886) vs 153 (18–610), p =  < 0.01, Alanine transferases 71 (5–937) vs 47 (8–271), p =  < 0.001) and decreased platelet count 207 (33–941) vs 252 (52- 641) (p = 0.021) compared to patients with HCC who were HBsAg-negative. Conclusions The prognosis of patients with HCC is poor in developing countries such as The Gambia, where screening programs and treatment modalities are scarce. Young males are disproportionately affected, and HBV is a major cause of HCC in The Gambia

Epidemiology of measles cases, vaccine effectiveness, and performance towards measles elimination in The Gambia

Introduction: In 2011, member states of the World Health Organization (WHO) Africa Regional Office (AFRO) resolved to eliminate Measles by 2020. Our study aims to assess The Gambia’s progress towards the set AFRO measles elimination target and highlight surveillance and immunisation gaps to better inform future measles prevention strategies. Material and methods: A retrospective review of measles surveillance data for the period 2011–2019, was extracted from The Gambia case-based measles surveillance database. WHO—UNICEF national coverage estimates were used for estimating national level MCV coverage. Measles post campaign coverage survey coverage estimates were used to estimate national measles campaign coverage. Results: One hundred and twenty-five of the 863 reported suspected cases were laboratory confirmed as measles cases. More than half (53.6%) of the confirmed cases have unknown vaccination status, 24% of cases were vaccinated, 52.8% of cases occurred among males, and 72.8% cases were among urban residents. The incidence of measles cases per million population was lowest (0) in 2011–2012 and highest in 2015 and 2016 (31 and 23 respectively). The indicator for surveillance sensitivity was met in all years except in 2016 and 2019. Children aged 5–9 years (Incidence Rate Ratio—IRR = 0.6) and residents of Central River region (IRR = 0.21) had lower measles risk whilst unvaccinated (Adjusted IRR = 5.95) and those with unknown vaccination status (IRR 2.21) had higher measles risk. Vaccine effectiveness was 89.5%. Conclusion: The Gambia’s quest to attain measles elimination status by 2020 has registered significant success but it is unlikely that all target indicators will be met. Vaccination has been very effective in preventing cases. There is variation in measles risk by health region, and it will be important to take it into account when designing prevention and control strategies. The quality of case investigations should be improved to enhance the quality of surveillance for decision making