COVID-19 vaccination implementation in 52 African countries: trajectory and implications for future pandemic preparedness.

INTRODUCTION: To end the COVID-19 pandemic, the WHO set a goal in 2021 to fully vaccinate 70% of the global population by mid-2022. We projected the COVID-19 vaccination trajectory in 52 African countries and compared the projected to the 'actual' or 'observed' coverage as of December 2022. We also estimated the required vaccination speed needed to have attained the WHO 70% coverage target by December 2022. METHODS: We obtained publicly available, country-reported daily COVID-19 vaccination data, covering the initial 9 months following the deployment of vaccines. We used a deterministic compartmental Susceptible-Exposed-Infectious-Recovered-type model and fit the model to the number of COVID-19 cases and vaccination coverage in each African country using a Markov chain Monte Carlo approach within a Bayesian framework. FINDINGS: Only nine of the 52 African countries (Tunisia, Cabo Verde, Lesotho, Mozambique, Rwanda, Seychelles, Morocco, Botswana and Mauritius) were on track to achieve full COVID-19 vaccination coverage rates ranging from 72% to 97% by the end of December 2022, based on their progress after 9 months of vaccine deployment. Of the 52 countries, 26 (50%) achieved 'actual' or 'observed' vaccination coverage rates within ±10 percentage points of their projected vaccination coverage. Among the countries projected to achieve <30% by December 2022, nine of them (Chad, Niger, Nigeria, South Sudan, Tanzania, Somalia, Zambia, Sierra Leone and Côte d'Ivoire) achieved a higher observed coverage than the projected coverage, ranging from 12.3 percentage points in South Sudan to 35.7 percentage points above the projected coverage in Tanzania. Among the 52 countries, 83% (43 out of 52) needed to at least double their vaccination trajectory after 9 months of deployment to reach the 70% target by December 2022. CONCLUSION: Our findings can guide countries in planning strategies for future global health emergencies and learning from each other, especially those that exceeded expectations and made significant progress towards the WHO's 2022 COVID-19 vaccination target despite projected poor coverage rates.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

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.

Provider and User Acceptability of Integrated Treatment for the Control of Malaria and Helminths in Saraya, South-Eastern Senegal.

Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria and neglected tropical diseases (NTD) by 2030. This qualitative study was conducted within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach. Randomly selected parents/caregivers of children enrolled in the trial, healthcare providers, trial staff, malaria, and NTD program managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥ 10 years, 15 trial staff, four healthcare providers, and two managers from the Senegal Ministry of Health were interviewed. Thirty-eight of the participants (66.7%) were males, and their ages ranged from 10 to 65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable, but the study participants expressed concerns about the taste, smell, and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10 to 14 years due to peer influence and gender-sensitive cultural beliefs. Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment program. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10 to 14 years in this approach.

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.

Addressing the challenges of implementing evidence-based prioritisation in global health.

Global health requires evidence-based approaches to improve health and decrease inequalities. In a roundtable discussion between health practitioners, funders, academics and policy-makers, we recognised key areas for improvement to deliver better-informed, sustainable and equitable global health practices. These focus on considering information-sharing mechanisms and developing evidence-based frameworks that take an adaptive function-based approach, grounded in the ability to perform and respond to prioritised needs. Increasing social engagement as well as sector and participant diversity in whole-of-society decision-making, and collaborating with and optimising on hyperlocal and global regional entities, will improve prioritisation of global health capabilities. Since the skills required to navigate drivers of pandemics, and the challenges in prioritising, capacity building and response do not sit squarely in the health sector, it is essential to integrate expertise from a broad range of fields to maximise on available knowledge during decision-making and system development. Here, we review the current assessment tools and provide seven discussion points for how improvements to implementation of evidence-based prioritisation can improve global health.

Prevalence of malaria-helminth co-infections among children living in a setting of high coverage of standard interventions for malaria and helminths: Two population-based studies in Senegal.

Background: Concurrent infections of Plasmodium falciparum with Soil Transmitted Helminths (STH) and Schistosoma spp are still a major public health problem among children living in Sub-Saharan Africa. We conducted two prospective studies among children living in urban and rural settings of Senegal, where control programmes for malaria, STH and schistosomiasis have been sustained, to determine the prevalence of malaria-helminth co-infection. Methods: We enrolled 910 children aged 1-14 years from Saraya and Diourbel districts of Senegal in June and November 2021, respectively. We collected finger-prick blood samples from the children for malaria parasite detection using microscopy and PCR methods. Stool samples were also collected and Kato-Katz and PCR methods were used to detect STH and S. mansoni; and Merthiolate-iodine-formalin (MIF) test for other intestinal protozoans. Urine samples were analyzed using a filtration test, Point of Care Circulating Cathodic Antigens (POC-CCA) and PCR methods for detection of S. haematobium. Statistical analyses were performed to compare the continuous and categorical variables across the two study sites and age groups, as well as using the adjusted Odds ratios (aOR) to explore risk factors for malaria-helminth co-infections. Results: The overall prevalence of polyparasitism with P. falciparum, STH, S. haematobium and S. mansoni among children in the two study sites was 2.2% (20/910) while prevalence of P. falciparum-S. haematobium co-infection was 1.1% (10/910); P. falciparum-S. mansoni 0.7% (6/910) and P. falciparum with any intestinal protozoan 2.4% (22/910). Co-infection was slightly higher among 5-14 year old children (17/629, 2.7%; 95% CI: 1.43-3.97) than 1-4 years (3/281, 1.1%; 95% CI: -0.12-2.32) and, in boys (13/567, 2.3%; 95% CI: 1.27-3.96) than girls (7/343, 2.1%; 95% CI: 0.52-3.48). Children aged 5-14 years (aOR = 3.37; 95% CI: 0.82-13.77, p = 0.09), who were boys (aOR = 1.44; 95% CI: 0.48-4.36, p = 0.51) and lived in Saraya (aOR = 1.27; 95% CI: 0.24-6.69, p = 0.77) had a higher risk of malaria-helminth co-infection than other age group, in girls and those who lived in Diourbel. Living in houses with spaces between the walls and roofs as well as frequent contacts with water during swimming were statistically significant risk factors for malaria-helminth co-infection. Conclusions: The prevalence of malaria-helminth co-infection is low in two districts in Senegal, possibly due to sustained implementation of effective control measures for malaria and NTDs. These findings could help to develop and implement strategies that would lead to elimination of malaria and helminths in the study areas.

Prevalence and distribution pattern of malaria and soil-transmitted helminth co-endemicity in sub-Saharan Africa, 2000-2018: A geospatial analysis.

BACKGROUND: Limited understanding exists about the interactions between malaria and soil-transmitted helminths (STH), their potential geographical overlap and the factors driving it. This study characterised the geographical and co-clustered distribution patterns of malaria and STH infections among vulnerable populations in sub-Saharan Africa (SSA). METHODOLOGY/PRINCIPAL FINDINGS: We obtained continuous estimates of malaria prevalence from the Malaria Atlas Project (MAP) and STH prevalence surveys from the WHO-driven Expanded Special Project for the Elimination of NTDs (ESPEN) from Jan 1, 2000, to Dec 31, 2018. Although, MAP provides datasets on the estimated prevalence of Plasmodium falciparum at 5km x 5km fine-scale resolution, we calculated the population-weighted prevalence of malaria for each implementation unit to ensure that both malaria and STH datasets were on the same spatial resolution. We incorporated survey data from 5,935 implementation units for STH prevalence and conducted the prevalence point estimates before and after 2003. We used the bivariate local indicator of spatial association (LISA analysis) to explore potential co-clustering of both diseases at the implementation unit levels among children aged 2-10 years for P. falciparum and 5-14 years for STH, living in SSA. Our analysis shows that prior to 2003, a greater number of SSA countries had a high prevalence of co-endemicity with P.falciparium and any STH species than during the period from 2003-2018. Similar prevalence and distribution patterns were observed for the co-endemicity involving P.falciparum-hookworm, P.falciparum-Ascaris lumbricoides and P.falciparum-Trichuris trichiura, before and after 2003. We also observed spatial variations in the estimates of the prevalence of P. falciparum-STH co-endemicity and identified hotspots across many countries in SSA with inter-and intra-country variations. High P. falciparum and high hookworm co-endemicity was more prevalent in West and Central Africa, whereas high P. falciparum with high A. lumbricoides and high P. falciparum with high T. trichiura co-endemicity were more predominant in Central Africa, compared to other sub-regions in SSA. CONCLUSIONS/SIGNIFICANCE: Wide spatial heterogeneity exists in the prevalence of malaria and STH co-endemicity within the regions and within countries in SSA. The geographical overlap and spatial co-existence of malaria and STH could be exploited to achieve effective control and elimination agendas through the integration of the vertical control programmes designed for malaria and STH into a more comprehensive and sustainable community-based paradigm.

Safety and effectiveness of delivering mass drug administration for helminths through the seasonal malaria chemoprevention platform among Senegalese children: study protocol for a randomised controlled trial.

BACKGROUND: Malaria remains a major health problem, especially in sub-Saharan Africa where more than 90% of the disease and where nearly all deaths occur in children. Adding to this high burden is the co-existence of intestinal and genito-urinary helminth infections. Existing control programmes for these helminths are operating sub-optimally. Conversely, a malaria prevention programme, called seasonal malaria chemoprevention (SMC), introduced in 2012 has achieved more than 75% treatment coverage and prevented 75-85% cases of uncomplicated and severe malaria in children. This encouraging development supports the need to explore strategies involving the integration of helminth control with successful platforms such as SMC. This would align worm and malaria control within the Sustainable Development Goals of ending the diseases of poverty and promoting health and well-being for those at risk. METHODS: This study will have quantitative and qualitative components. The quantitative component will be a three-arm, observer-blind, placebo-controlled, interventional study of co-administration of SMC and anthelminthic drugs to pre-school and school-age children in Saraya district, southeast Senegal. Six hundred children aged 1-14 years will be randomly assigned to receive either SMC drugs only, SMC drugs and praziquantel or SMC drugs and albendazole and praziquantel at a ratio of 1:1:1. The primary outcome will be solicited and unsolicited adverse reactions to the study medications. The secondary outcomes will be the prevalence and intensity of Plasmodium-helminth co-infection and the prevalence of anaemia and mean haemoglobin concentration. The qualitative component of the study will include the conduct of structured interviews to assess the acceptability, feasibility, enablers and barriers to the combined use of anthelminthic and SMC drugs among randomly selected parents/caregivers of children enrolled in the study and health care workers responsible for the delivery of the combined services. DISCUSSION: This study will provide evidence to boost the public health recommendations for combined malaria and helminth control. If successful, this project will reinforce the evidence that health care systems in developing countries can be comprehensive health management rather than focussed on vertical management of a single disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05354258. Registered on 28 April 2022. PACTR202204794105273. Registered on 25 April 2022.

Incidence of Catastrophic Health Expenditures Amongst Hospitalized Neonates in Ekiti, Southwest Nigeria.

Background: Neonatal illnesses require huge spending due to prolonged hospital stay. The management of these illnesses is usually financed by individual families which in most instances are living below the poverty line. This healthcare financing method can readily push families into catastrophic spending on health. Aim: To ascertain the average cost of managing common neonatal illnesses and the financial burden, it constitutes to families in Ekiti State, southwest Nigeria. Methods: We conducted a cross-sectional study on the out-of-pocket spending involved in managing neonates admitted into and discharged from the SCBU of the Ekiti State University Teaching Hospital, Ado-Ekiti, southwest Nigeria. Data collected included the monthly family income, the money spent on drugs, laboratory investigations and the hospital bill using a purposely designed structured questionnaire. Healthcare spending greater than 10% of the overall family income was described as catastrophic health spending (CHS). Results: The medical bills for most (95%) of the 119 study participants were paid through the out-of-pocket means and 81.5% of the families spent more than 10% of their monthly earnings (CHS) to settle medical bills. Close to 50% of the families belonged to the lower social economic class. The median (IQR) duration of hospital stay was 2.75 days (3.0-8.0). The median (IQR) total expenditure was N24,500.00 (N13,615.00-N41,487.50). The median (IQR) expenditure for the treatment of prematurity was highest at N55,075.00 (USD 133.10) [N27,350.00 (USD 66.10)-N105,737.50 (USD 255.53)] and more than 60.5% of the expenses was on hospital utilities and consumables. The length of hospital stay showed a robust positive correlation with the total hospital bill (r = 0.576, P < 0.001). Conclusion: Neonatal illnesses put many households at risk of catastrophic health spending. There is need for increased government investment in health and extension of the health insurance scheme to all the citizens of the country.

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.

Caregivers' perception of risk for malaria, helminth infection and malaria-helminth co-infection among children living in urban and rural settings of Senegal: A qualitative study.

The parasites causing malaria, soil-transmitted helminthiasis and schistosomiasis frequently co-exist in children living in low-and middle-income countries, where existing vertical control programmes for the control of these diseases are not operating at optimal levels. This gap necessitates the development and implementation of strategic interventions to achieve effective control and eventual elimination of these co-infections. Central to the successful implementation of any intervention is its acceptance and uptake by caregivers whose perception about the risk for malaria-helminth co-infection has been little documented. Therefore, we conducted a qualitative study to understand the caregivers' perspectives about the risk as well as the behavioural and social risk factors promoting malaria-helminth co-infection among pre-school and school-age children living in endemic rural and urban communities in Senegal. In June and December 2021, we conducted individual and group interviews, and participant observations, among 100 primary caregivers of children recruited from Saraya villages in southeast Senegal and among leaders and teachers of Koranic schools in Diourbel, western Senegal. Our findings showed that a majority of the study participants in the two settings demonstrated a high level of perception of risk for malaria and acceptable awareness about handwashing practices, but had misconceptions that malaria-helminth co-infection was due to a combination of excessive consumption of sugary food and mosquito bites. Our observations revealed many factors in the house structures, toilet practices and handwashing with ashes and sands, which the caregivers did not consider as risks for malaria-helminth co-infections. These findings underscore the need to promote caregivers' awareness about the existence and risk of malaria-helminth co-infection in children. This approach would assist in addressing the caregivers' misconceptions about the occurrence of the co-infection and could enhance their uptake of the strategic interventions targeted at achieving control and subsequent elimination of malaria and helminth co-infection.

Priorities for global access to life-saving interventions during public health emergencies: Crisis nationalism, solidarity or charity?

Access to COVID-19-vaccines by the global poor has unveiled the impact of global health and scientific inequities on access to life saving interventions during public health emergencies (PHE). Despite calls for global solidarity to ensure equitable global access to COVID-19 vaccines, wealthy countries both in the north and southern hemisphere may find a charity-based approach more appealing and are using the opportunity to forge neo-colonial cooperation ties with some African countries. Solidarity is undoubtedly an ideal equity-based principle of public health emergency of international concern (PHEIC). However, its application may be wanting especially as crisis nationalism is more likely to inform the public health policy of any country during a PHEIC, even when they are strong advocates of global solidarity. African countries, on the other hand, must re-appraise their heavy reliance on international aids during PHE and recognise the importance of boosting their epidemic preparedness including research and translation of its findings to practice.

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.

Tracking the uptake and trajectory of COVID-19 vaccination coverage in 15 West African countries: an interim analysis.

The African Union Bureau of Heads of State and Government endorsed the COVID-19 Vaccine Development and Access Strategy to vaccinate at least 60% of each country's population with a safe and efficacious vaccine by 2022, to achieve the population-level immunity needed to bring the pandemic under control. Using publicly available, country-level population estimates and COVID-19 vaccination data, we provide unique insights into the uptake trends of COVID-19 vaccinations in the 15 countries that comprise the Economic Community of West Africa States (ECOWAS). Based on the vaccination rates in the ECOWAS region after three months of commencing COVID-19 vaccinations, we provide a projection of the trajectory and speed of vaccination needed to achieve a COVID-19 vaccination coverage rate of at least 60% of the total ECOWAS population. After three months of the deployment of COVID-19 vaccines across the ECOWAS countries, only 0.27% of the region's total population had been fully vaccinated. If ECOWAS countries follow this trajectory, the sub-region will have less than 1.6% of the total population fully vaccinated after 18 months of vaccine deployment. Our projection shows that to achieve a COVID-19 vaccination coverage of at least 60% of the total population in the ECOWAS sub-region after 9, 12 and 18 months of vaccine deployment; the speed of vaccination must be increased to 10, 7 and 4 times the current trajectory, respectively. West African governments must deploy contextually relevant and culturally acceptable strategies for COVID-19 vaccine procurements, distributions and implementations in order to achieve reasonable coverage and save lives, sooner rather than later.

Malaria and helminth co-infections in children living in endemic countries: A systematic review with meta-analysis.

BACKGROUND: Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane's Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger's test (bias if p<0.1). Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7-23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37-1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28-0.64). When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03-1.65). A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59-2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30-3.14). CONCLUSIONS/SIGNIFICANCE: The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.

Lessons from the Ebola epidemics and their applications for COVID-19 pandemic response in sub-Saharan Africa.

COVID-19, caused by a novel coronavirus named SARS-CoV-2, was identified in December 2019, in Wuhan, China. It was first confirmed in sub-Saharan Africa in Nigeria on 27 February 2020 and has since spread quickly to all sub-Saharan African countries, causing more than 111,309 confirmed cases and 2,498 deaths as of 03 June 2020. The lessons learned during the recent Ebola virus disease (EVD) outbreaks in some sub-Saharan African countries were expected to shape and influence the region's responses to COVID-19 pandemic. However, some of the challenges associated with the management of the EVD outbreaks persist and create obstacles for the effective management of the COVID-19 pandemic. This article describes the commonalities between the EVD epidemics and COVID-19 pandemic, with a view to draw on lessons learned to effectively tackle the ongoing pandemic. Key successes, failures and lessons learned from previous EVD outbreaks are discussed. Recommendations on how these lessons can be translated to strengthen the COVID-19 response in sub-Saharan Africa are provided.

Clinical presentations and management of COVID-19 infected children seen in a district health facility in Kambia, northern Sierra Leone.

Studies reporting the clinical presentations of COVID-19 in children in sub-Saharan Africa are few, especially from resource-constrained countries. This case series reports the demographic and clinical characteristics and laboratory findings of confirmed cases of COVID-19 in children seen at a district hospital in Sierra Leone. This is a report of nine COVID-19 paediatric cases managed at a secondary level hospital in Kambia District, Northern Sierra Leone. Each child was detected by contact tracing after an infected adult was identified by the COVID-19 response team. The clinical symptoms at presentation, clinical courses, and treatments instituted and patient outcomes are discussed in the context of the facilities available at a typical West African district hospital. Nine out of 30 individuals with confirmed COVID-19 infection who presented to the hospital from 24 April to 20 September 2020 and who were admitted to the isolation center of the hospital were in the paediatric age group. The mean age (SD) and median (IQR) of the children were 69.0 ± 51.7months and 84.0 (10.5, 108.0) months, respectively; five (55.6%) were males. The children were asymptomatic or only had mild illnesses and none required intranasal oxygen or ventilatory support. In the five symptomatic children, the most common symptoms were fever (40%) and cough (40%). All children had normal haemoglobin, platelet and white blood cell (WBC) count. Four children had a positive malaria test and were treated with a complete course of anti-malaria medications. No child received steroid or had specific anti-COVID-19 treatment. All children stayed in the isolation center for 14 days and were re-tested for COVID-19 two weeks after initial diagnosis. No complications have been reported in any of them since discharge. The proportion of children among COVID-19 infected cases seen in a rural community in Sierra Leone was 30%. Fever was the most common symptom and malaria was confirmed in 40% of the infected children. This has significant implication on the diagnosis of COVID-19 in malaria-endemic settings and on how best to manage children who present with fever during the COVID-19 pandemic.

Considerations for community engagement when conducting clinical trials during infectious disease emergencies in West Africa.

Community engagement in research, including public health related research, is acknowledged as an ethical imperative. While medical care and public health action take priority over research during infectious disease outbreaks, research is still required in order to learn from epidemic responses. The World Health Organisation developed a guide for community engagement during infectious disease epidemics called the Good Participatory Practice for Trials of Emerging (and Re-emerging) Pathogens that are Likely to Cause Severe Outbreaks in the Near Future and for which Few or No Medical Counter-Measures Exist (GPP-EP). This paper identified priorities for community engagement for research conducted during infectious disease outbreaks drawing on discussions held with a purposive sample of bioethicists, social scientists, researchers, policy makers and laypersons who work with ethics committees in West Africa. These perspectives were considered in the light of the GPP-EP, which adds further depth and dimension to discussions on community engagement frameworks. It concludes that there is no presumptive justification for the exclusion of communities in the design, implementation and monitoring of clinical trials conducted during an infectious disease outbreak. Engagement that facilitates collaboration rather than partnership between researchers and the community during epidemics is acceptable.