Mapping of intermediate host snails for schistosomiasis in the Democratic Republic of Congo: a systematic review.

Schistosomiasis is a snail-borne disease that has a considerable impact on human and animal health, particularly in sub-Saharan Africa. The intermediate hosts of the schistosome parasites are freshwater snails of the genera Biomphalaria Preston, 1910 and Bulinus Müller, 1781. In order to identify existing gaps in the spread of the disease in the Democratic Republic of Congo (DRC), this study compiled the available knowledge of the distribution, population dynamics and ecology of the intermediate hosts of schistosomiasis. A systematic literature search was conducted in PubMed, Embase and Scopus for all malacological studies on schistosoma intermediate hosts in DRC published between 1927 and October 2022. A total of 55 records were found, of which 31 met the inclusion criteria: these were published field and experimental studies conducted in the DRC and focused on snails as intermediate hosts of schistosomes. The analysis of these studies revealed that more up-to-date data on the distribution of snail intermediate hosts in the DRC are needed. Moreover, ecological factors have been less studied for Bulinus species than for Biomphalaria species. These factors play a crucial role in determining suitable snail habitats, and the lack of comprehensive information poses a challenge in snail control. This review makes it clear that there are no current malacological data in the DRC. There is a clear need for molecular and ecological research to update the exact species status and population dynamics of all potential intermediate host species. This will facilitate targeted snail control measures that complement drug treatment in the control of schistosomiasis in the country.

An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations.

INTRODUCTION: Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations. METHODS: To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed. RESULTS: Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support. CONCLUSION: The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.

Prevention of Malaria in Pregnant Women and Its Effects on Maternal and Child Health, the Case of Centre Hospitalier de Kingasani II in the Democratic Republic of the Congo.

This study aimed to evaluate scientific evidence of the benefit of the use of insecticide-treated nets (ITNs) and Intermittent preventive treatment (IPT) on the birth weight of newborns and the hemoglobin level of the mother when used to prevent malaria during pregnancy. This cross-sectional analytical study was conducted on 467 hospitalized women in the Maternity Ward of Centre Hospitalier de Kingasani II, in the Democratic Republic of the Congo. Data were collected using a structured questionnaire that was pre-tested during a face-to-face interview. Apart from basic statistics, the chi-square test was used to compare proportions. Multivariate analysis (logistic regression) was used to identify variables significantly associated with the 95% confidence interval (CI). The ITN ownership rate was 81% (95% CI: 77-84) and the ITN use rate was 66% (95% CI: 62-70). Sixty-five percent (95% CI: 60-69) reported having received at least three doses of IPT during pregnancy with sulfadoxine-pyramethemine (IPTp-SP). There was a statistically significant difference in hemoglobin levels between hospitalized women who did not use the ITN (9.4 g/dL IIQ: 8.7-9.9) and those who did (11 g/dL IIQ: 9.8-12.2). The non-use of the ITN was associated with low birth weight (aOR = 3.6; 95% CI: 2.1-6.2; p < 0.001) and anemia in pregnant women (cOR = 2.41; 95% CI: 1.16-5.01; p = 0.018). The use of ITN and taking at least three doses of ITP during pregnancy are associated with good birth weight. The number of doses of IPTp received during antenatal care is associated with the maternal hemoglobin level in the third trimester of pregnancy.

Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomised, phase 2 trial.

BACKGROUND: Health-care providers and front-line workers are at risk of contracting Ebola virus disease during an Ebola virus outbreak and consequently of becoming drivers of the disease. We aimed to assess the long-term immunogenicity of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen and the safety of and immune memory response to an Ad26.ZEBOV booster vaccination at 1 year or 2 years after the first dose in this at-risk population. METHODS: This open-label, single-centre, randomised, phase 2 trial was conducted at one study site within a hospital in Boende, Democratic Republic of the Congo. Adult health-care providers and front-line workers, excluding those with a known history of Ebola virus disease, were vaccinated with a two-dose heterologous regimen administered at a 56-day interval via a 0·5 mL intramuscular injection in the deltoid muscle, comprising Ad26.ZEBOV as the first dose and MVA-BN-Filo as the second dose. After the initial vaccination on day 1, participants were randomly assigned (1:1) via randomisation envelopes, opened in a sequential order, to receive an Ad26.ZEBOV booster vaccination at 1 year (group 1) or 2 years (group 2) after the first dose. We present the secondary and exploratory objectives of the trial-results of the primary objective have been published elsewhere. We measured immunogenicity at six timepoints per group as geometric mean concentrations (GMCs) of Ebola virus glycoprotein-specific IgG binding antibodies, using the Filovirus Animal Non-Clinical Group ELISA. We assessed serious adverse events occurring up to 6 months after the last dose and local and systemic solicited and unsolicited adverse events reported for 7 days after the booster vaccination. Antibody responses were analysed per protocol, serious adverse events per full analysis set (FAS), and adverse events for all boosted FAS participants. This trial is registered as completed on ClinicalTrials.gov (NCT04186000). FINDINGS: Between Dec 18, 2019, and Feb 8, 2020, 699 health-care providers and front-line workers were enrolled and 698 were randomly assigned (350 to group 1 and 348 to group 2 [FAS]); 534 (77%) participants were male and 164 (23%) were female. 319 in group 1 and 317 in group 2 received the booster. 29 (8%) in group 1 and 26 (7%) in group 2 did not complete the study, mostly due to loss to follow-up or moving out of the study area. In both groups, injection-site pain or tenderness (87 [27%] of 319 group 1 participants vs 90 [28%] of 317 group 2 participants) and headache (91 [29%] vs 93 [29%]) were the most common solicited adverse events related to the investigational product. One participant (in group 2) had a related serious adverse event after booster vaccination (fever of ≥40·0°C). Before booster vaccination, Ebola virus glycoprotein-specific IgG binding antibody GMCs were 279·9 ELISA units (EU) per mL (95% CI 250·6-312·7) in 314 group 1 participants (1 year after first dose) and 274·6 EU/mL (242·1-311·5) in 310 group 2 participants (2 years after first dose). These values were 5·2 times higher in group 1 and 4·9 times higher in group 2 than before vaccination on day 1. 7 days after booster vaccination, these values increased to 10 781·6 EU/mL (9354·4-12 426·4) for group 1 and 10 746·9 EU/mL (9208·7-12 542·0) for group 2, which were approximately 39 times higher than before booster vaccination in both groups. 1 year after booster vaccination in 299 group 1 participants, a GMC that was 7·6-times higher than before booster vaccination was still observed (2133·1 EU/mL [1827·7-2489·7]). INTERPRETATION: Overall, the vaccine regimen and booster dose were well tolerated. A similar and robust humoral immune response was observed for participants boosted 1 year and 2 years after the first dose, supporting the use of the regimen and flexibility of booster dose administration for prophylactic vaccination in at-risk populations. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking and Coalition for Epidemic Preparedness Innovations.

Longitudinal assessment of an Ebola vaccine trial understanding among healthcare providers in the Democratic Republic of the Congo.

BACKGROUND: The long-term retention of information disclosed during the informed consent in clinical trials lasting over a year cannot be guaranteed for all volunteers. This study aimed to assess the level of participants' retention and understanding of the trial information after two years of participation in a vaccine trial. METHODS: In total, 699 health care providers (HCPs) and frontline workers were enrolled in the EBL2007 vaccine trial conducted between February 2019 and September 2022 in the Health District of Boende, Democratic Republic of the Congo (DRC). Individual scores obtained from a questionnaire (test of understanding, TOU), specifically designed to assess the understanding of the consent at baseline, were collected before the clinical trial started and at one-year and two-year intervals. RESULTS: TOU scores were high in the beginning of the trial (median TOU = 10/10), but significantly decreased in both the first and second years following (median TOU = 8/10 in year 1 and median TOU = 9/10 in year 2, p-value < 0.0001). The decrease in scores was significantly higher among individuals with occupations requiring shorter education such as midwives (median TOU = 7/10 in year 1 and 8/10 in year 2, pvalue = 0.025). Furthermore, older participants exhibited poorer retention of information compared to younger individuals (median TOU = 8/10 vs 9/10, p-value = 0.007). CONCLUSION: We observed a significant decline in the informational knowledge of informed consent, specifically in terms of basic knowledge on the study vaccine and trial procedures. As participant safety and understanding is a paramount ethical concern for researchers, it is crucial for participants to fully comprehend the study's objectives and potential risks. Therefore, our findings suggest the need for clinical researchers to re-explain participants to optimize the protection of their rights and wellbeing during the research.

Safety and Immunogenicity of the Heterologous 2-Dose Ad26.ZEBOV, MVA-BN-Filo Vaccine Regimen in Health Care Providers and Frontliners of the Democratic Republic of the Congo.

BACKGROUND: In response to recent Ebola epidemics, vaccine development against the Zaire ebolavirus (EBOV) has been fast-tracked in the past decade. Health care providers and frontliners working in Ebola-endemic areas are at high risk of contracting and spreading the virus. METHODS: This study assessed the safety and immunogenicity of the 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine regimen (administered at a 56-day interval) among 699 health care providers and frontliners taking part in a phase 2, monocentric, randomized vaccine trial in Boende, the Democratic Republic of Congo. The first participant was enrolled and vaccinated on 18 December 2019. Serious adverse events were collected up to 6 months after the last received dose. The EBOV glycoprotein FANG ELISA (Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay) was used to measure the immunoglobulin G-binding antibody response to the EBOV glycoprotein. RESULTS: The vaccine regimen was well tolerated with no vaccine-related serious adverse events reported. Twenty-one days after the second dose, an EBOV glycoprotein-specific binding antibody response was observed in 95.2% of participants. CONCLUSIONS: The 2-dose vaccine regimen was well tolerated and led to a high antibody response among fully vaccinated health care providers and frontliners in Boende.

Conducting an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned.

Conducting a vaccine trial in a low- and middle-income country (LMIC) can present unique challenges and lessons learned. This Ebola vaccine trial, enrolling 699 healthcare providers and frontliners and jointly set up by the University of Antwerp (Sponsor) and the University of Kinshasa (Principal Investigator (PI)), was conducted in Boende, a remote city in the Democratic Republic of the Congo (DRC), between December 2019 and October 2022 (ClinicalTrials.gov: NCT04186000). While being bound by strict ICH-GCP and international funder regulations, this trial, exemplary for being a public-private partnership, required collaboration between several international stakeholders (e.g., two universities, a pharmaceutical company, and a clinical research organization), local communities and government agencies. Here we address several logistical and administrative challenges, cultural differences, language barriers and regulatory, political, and ethical considerations over the trial's 2.5-year duration, while tailoring and adapting the study to the specific local context. Lessons learned include the importance of clear communication with participants in all phases of the study, but also within the study team and among different stakeholders. Challenges, mitigations, and lessons learned are presented in nine categories (e.g., safety management; trial documentation, tools, and materials; communication, staff training and community engagement/sensitization; financial and administrative hurdles; and more). Ultimately, to reach the successful end of the vaccine trial in this remote Ebola endemic area in the DRC, careful planning, collaboration, and great flexibility and adaptability was often required from all involved partners. Despite the encountered challenges, the vaccine trial discussed in this paper was able to obtain high participant retention rates (i.e., 92% of participants completed the study). We hope that other international teams aspiring to conduct similar trials in remote areas of LMICs can learn from the way our challenges were addressed, mitigations developed, and lessons were learned.

Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo.

BACKGROUND: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. METHODS: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. RESULTS: The median parasite density by qPCR was 292 p/µL of blood [IQR (49.7-1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6-63.6)], [81.7% (95%CI 74.7-87.3)] and [88% (95% CI 81.9-92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6-99.5), 95.2% (95% CI 92.5-97.2) and 94.4% (95% CI 91.4-96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1-75.3) compared to 68% (95% CI 53.3-80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8-98.7) for RDT versus 100% (95% CI 82.3-100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10-33.7) and 47.3% (95% CI 24.4-71.1) respectively. CONCLUSIONS: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity.

Low seroprevalence of Ebola virus in health care providers in an endemic region (Tshuapa province) of the Democratic Republic of the Congo.

INTRODUCTION: A serosurvey among health care providers (HCPs) and frontliners of an area previously affected by Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC) was conducted to assess the seroreactivity to Ebola virus antigens. METHODS: Serum samples were collected in a cohort of HCPs and frontliners (n = 698) participants in the EBL2007 vaccine trial (December 2019 to October 2022). Specimens seroreactive for EBOV were confirmed using either the Filovirus Animal Nonclinical Group (FANG) ELISA or a Luminex multiplex assay. RESULTS: The seroreactivity to at least two EBOV-Mayinga (m) antigens was found in 10 (1.4%: 95% CI, 0.7-2.6) samples for GP-EBOV-m + VP40-EBOV-m, and 2 (0.3%: 95% CI, 0.0-1.0) samples for VP40-EBOV-m + NP-EBOV-m using the Luminex assay. Seroreactivity to GP-EBOV-Kikwit (k) was observed in 59 (8.5%: 95%CI, 6.5-10.9) samples using FANG ELISA. CONCLUSION: In contrast to previous serosurveys, a low seroprevalence was found in the HCP and frontline population participating in the EBL2007 Ebola vaccine trial in Boende, DRC. This underscores the high need for standardized antibody assays and cutoffs in EBOV serosurveys to avoid the broad range of reported EBOV seroprevalence rates in EBOV endemic areas.

Challenges to COVID-19 vaccine introduction in the Democratic Republic of the Congo - a commentary.

COVID-19 vaccination in the Democratic Republic of the Congo (DRC) began in April 2021. A month later, most COVID-19 vaccine doses were reallocated to other African countries, due to low vaccine uptake and the realization that the doses would expire before use. Based on data available on 13 August 2022, 2.76% of the DRC population had been fully vaccinated with last dose of primary series of COVID-19 vaccine, placing the country second to last in Africa and in the last five in global COVID-19 vaccination coverage. The DRC's reliance on vaccine donations requires continuous adaptation of the vaccine deployment plan to match incoming COVID-19 vaccines shipments. Challenges in planning vaccine deployments, vaccinating priority populations, coordinating, and implementing the communications plan, disbursing funds, and conducting supervision of vaccination activities have contributed to low COVID-19 vaccine coverage. In addition, the spread of rumors through social media and by various community and religious leaders resulted in high levels of vaccine hesitancy. A strong risk communication and community engagement plan, coupled with innovative efforts to target the highest-risk populations are critical to increase vaccine uptake during the next phase of COVID-19 vaccine introduction.

Setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned.

Since the largest Ebola outbreak in West Africa (2013-2016) highlighted the potential threat of the Ebola virus to the world, several vaccines have been under development by different pharmaceutical companies. To obtain vaccine licensure, vaccine trials assessing the safety, immunogenicity and efficacy of new vaccines among different populations (e.g. different in age, gender, race, and ethnicity) play a crucial role. However, while this deadly disease mainly affects Central and West Africa, clinical trial regulations are becoming increasingly complex and consequently more expensive, influencing the affected low- and middle-income countries (LMICs) in performing high quality clinical trials. Consequently, the completion of such trials in LMICs takes more time and vaccines and drugs take longer to be licensed. To overcome some of the obstacles faced, the EBOVAC3 consortium, funded by the European Union's Innovative Medicines Initiative and the Coalition for Epidemic Preparedness Innovations, enabled high quality vaccine trials in Central and West Africa through extensive North-South collaborations. In this article, the encountered challenges, mitigations, recommendations and lessons learned from setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of Congo are presented. These challenges are grouped into eight categories: (1) Regulatory, political and ethical, (2) Trial documents, (3) International collaborations, (4) Local trial staff, (5) Community engagement and sensitization, (6) Logistics, (7) Remoteness and climate conditions, (8) Financial. By sharing the encountered challenges, implemented mitigations and lessons learned for each of these categories, we hope to prepare and inform other researchers aspiring a well-functioning clinical trial unit in similar remote settings in LMICs. ClinicalTrials.gov identifier: NCT04186000.

Open-label, randomised, clinical trial to evaluate the immunogenicity and safety of a prophylactic vaccination of healthcare providers by administration of a heterologous vaccine regimen against Ebola in the Democratic Republic of the Congo: the study protocol.

INTRODUCTION: This article describes the protocol of an Ebola vaccine clinical trial which investigates the safety and immunogenicity of a two-dose prophylactic Ebola vaccine regimen comprised of two Ebola vaccines (Ad26.ZEBOV and MVA-BN-Filo) administered 56 days apart, followed by a booster vaccination with Ad26.ZEBOV offered at either 1 year or 2 years (randomisation 1:1) after the first dose. This clinical trial is part of the EBOVAC3 project (an Innovative Medicines Initiative 2 Joint Undertaking), and is the first to evaluate the safety and immunogenicity of two different booster vaccination arms in a large cohort of adults. METHODS AND ANALYSIS: This study is an open-label, monocentric, phase 2, randomised vaccine trial. A total of 700 healthcare providers and frontliners are planned to be recruited from the Tshuapa province in the Democratic Republic of the Congo (DRC). The primary and secondary objectives of the study assess the immunogenicity of the first (Ad26.ZEBOV), second (MVA-BN-Filo) and booster (Ad26.ZEBOV) dose. Immunogenicity is assessed through the evaluation of EBOV glycoprotein binding antibody responses after vaccination. Safety is assessed through the collection of serious adverse events from the first dose until 6 months post booster vaccination and the collection of solicited and unsolicited adverse events for 1 week after the booster dose. ETHICS AND DISSEMINATION: The protocol was approved by the National Ethics Committee of the Ministry of Health of the DRC (n°121/CNES/BN/PMMF/2019). The clinical trial was registered on 4 December 2019 on ClinicalTrials.gov. Trial activities are planned to finish in October 2022. All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of the trial will be added on ClinicalTrials.gov, published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT04186000; Pre-results.

Use of Iris Scanning for Biometric Recognition of Healthy Adults Participating in an Ebola Vaccine Trial in the Democratic Republic of the Congo: Mixed Methods Study.

BACKGROUND: A partnership between the University of Antwerp and the University of Kinshasa implemented the EBOVAC3 clinical trial with an Ebola vaccine regimen administered to health care provider participants in Tshuapa Province, Democratic Republic of the Congo. This randomized controlled trial was part of an Ebola outbreak preparedness initiative financed through Innovative Medicines Initiative-European Union. The EBOVAC3 clinical trial used iris scan technology to identify all health care provider participants enrolled in the vaccine trial, to ensure that the right participant received the right vaccine at the right visit. OBJECTIVE: We aimed to assess the acceptability, accuracy, and feasibility of iris scan technology as an identification method within a population of health care provider participants in a vaccine trial in a remote setting. METHODS: We used a mixed methods study. The acceptability was assessed prior to the trial through 12 focus group discussions (FGDs) and was assessed at enrollment. Feasibility and accuracy research was conducted using a longitudinal trial study design, where iris scanning was compared with the unique study ID card to identify health care provider participants at enrollment and at their follow-up visits. RESULTS: During the FGDs, health care provider participants were mainly concerned about the iris scan technology causing physical problems to their eyes or exposing them to spiritual problems through sorcery. However, 99% (85/86; 95% CI 97.1-100.0) of health care provider participants in the FGDs agreed to be identified by the iris scan. Also, at enrollment, 99.0% (692/699; 95% CI 98.2-99.7) of health care provider participants accepted to be identified by iris scan. Iris scan technology correctly identified 93.1% (636/683; 95% CI 91.2-95.0) of the participants returning for scheduled follow-up visits. The iris scanning operation lasted 2 minutes or less for 96.0% (656/683; 95% CI 94.6-97.5), and 1 attempt was enough to identify the majority of study participants (475/683, 69.5%; 95% CI 66.1-73.0). CONCLUSIONS: Iris scans are highly acceptable as an identification tool in a clinical trial for health care provider participants in a remote setting. Its operationalization during the trial demonstrated a high level of accuracy that can reliably identify individuals. Iris scanning is found to be feasible in clinical trials but requires a trained operator to reduce the duration and the number of attempts to identify a participant. TRIAL REGISTRATION: ClinicalTrials.gov NCT04186000; https://clinicaltrials.gov/ct2/show/NCT04186000.

Algorithm for the support of non-related (serious) adverse events in an Ebola vaccine trial in the Democratic Republic of the Congo.

Implementing an Ebola vaccine trial in a remote area in the Democratic Republic of the Congo (DRC), and being confronted with a dysfunctional health care system and acute unmet health needs of participants, ethical considerations were made regarding the ancillary care obligations of the sponsor and researchers. Spurred by the occurrence of non-related (serious) adverse events (NR-SAEs), the Universities of Antwerp and Kinshasa jointly developed an algorithm, accompanied by an algorithm policy. The algorithm consists of a set of consecutive questions with binary response options, leading to structured, non-arbitrary and consistent support and management for each NR-SAE. It is the result of dialogue and collaboration between the sponsor (University of Antwerp) and the principal investigator (University of Kinshasa), consultation of literature, and input of research ethics and social sciences experts. The characteristics of the project and its budgetary framework were taken into account, as well as the local socioeconomic and healthcare situation. The algorithm and related policy have been approved by the relevant ethics committee (EC), so field implementation will begin when the study activities resume in November 2021. Lessons learnt will be shared with the relevant stakeholders within and outside DRC.If NR-SAEs are not covered by a functioning social welfare system, sponsors and researchers should develop a feasible, standardised and transparent approach to the provision of ancillary care. National legislation and contextualised requirements are therefore needed, particularly in low/middle-income countries, to guide researchers and sponsors in this process. Protocols, particularly of clinical trials conducted in areas with 'access to care' constraints, should include adequate ancillary care arrangements. Furthermore, it is essential that local ECs systematically require ancillary care provisions to enhance the well-being and protection of the rights of research participants. This project was funded by the European Union's Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations, and the Coalition for Epidemic Preparedness Innovations.

Analyse des modalités de financement des soins de santé en République démocratique du Congo : une revue systématique

Contexte et objectif. Dans l'optique de la couverture universelle de la santé (CUS), il est urgent de repenser le système de financement de la santé dans les pays à faibles revenus, y compris en RDC. La présente étude avait pour objectif de faire un état de lieux de différentes modalités de financement des soins de santé en vue d'une mise en oeuvre d'une politique adaptée de la CUS. Méthodes. Analyse narrative et systématique des travaux publiés sur le financement des soins en RDC, entre 1980 et 2018, selon les directives PRISMA, en utilisant les moteurs de recherche Medline/Pubmed et Google Scholar. Résultats. Au total 27 articles ont été sélectionnés sur 1.429 et ont permis de faire une analyse thématique. Le paiement direct des soins est le mode le plus répandu, soit sous forme de paiement à l'acte, soit sous forme de paiement forfaitaire généralement subventionné en partie. Quelle que soit sa forme, le paiement direct exclut un grand nombre de personnes et constitue une barrière considérable à l'accès aux soins. Le prépaiement est considéré par la population comme un mandat de voyage donnant accès à des soins de santé moins chers. Mais, l'adhésion aux mutuelles de santé demeure faible à cause du très faible pouvoir d'achat et de la qualité des services de santé qui ne suit pas. La politique de subvention de paiement des soins existe sous la forme de gratuité de soins et d'incitations financières dont notamment le cash transfert et le financement basé sur les résultats. Quelle que soit la forme de subvention, il y a une amélioration de l'utilisation de services. Mais cette performance n'est pas pérenne. Conclusion. Le paiement direct demeure encore le plus répandu, mais le prépaiement semble être le mode qui favorise le mieux l'accès aux soins. Plus de données probantes sont encore nécessaires pour soutenir telle ou telle autre approche

Efficacy and safety of intermittent preventive treatment in schoolchildren with sulfadoxine/pyrimethamine (SP) and SP plus piperaquine in Democratic Republic of the Congo: a randomised controlled trial.

In endemic areas, malaria and its adverse effects in schoolchildren may be prevented by intermittent preventive treatment (IPTsc). However, the most appropriate drug regimen for IPTsc remains to be identified. A randomised controlled trial was conducted in Kinshasa, DRC. Enrolled schoolchildren were assigned to a passive control arm (n = 212), sulfadoxine/pyrimethamine (SP) (n = 202) or SP plus piperaquine (SP/PQ) (n = 202). The primary endpoint was haemoglobin (Hb) change. Secondary endpoints were anaemia, parasitaemia prevalence and clinical malaria incidence. Data were analysed by modified intention-to-treat (mITT) and per-protocol. A linear mixed mode was used due to repeated measurements. Of 616 enrolled children, 410 (66.6%) were eligible for mITT analysis. The control arm was used as reference. After 12 months, the Hb level increased by 0.20 g/dL (95% CI -0.61 to 0.47; P = 0.168) and 0.39 g/dL (0.12-0.66; P <0.01) in the SP and SP/PQ arms, respectively. SP treatment reduced anaemia, malaria parasitaemia and clinical malaria by 10% (0-20%; P = 0.06), 19% (2-33%; P = 0.042) and 25% (-32 to 57%; P = 0.37), respectively. The corresponding values for SP/PQ were 28% (19-37%; P <0.001), 40% (26-52%; P <0.001) and 58% (17-79%; P <0.01). No deaths or severe adverse events (SAEs) were observed. SP/PQ offered substantial protection against anaemia, malaria parasitaemia and clinical malaria and showed no SAEs. SP/PQ, a combination of two long-acting non-artemisinin-based antimalarials, may be a valuable option for IPTsc in Africa.

Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review.

BACKGROUND: Intermittent preventive treatment (IPT) is a proven malaria control strategy in infants and pregnancy. School-aged children represent 26 % of the African population, and an increasing percentage of them are scholarized. Malaria is causing 50 % of deaths in this age group and malaria control efforts may shift the malaria burden to older age groups. Schools have been suggested as a platform for health interventions delivery (deworming, iron-folic acid, nutrients supplementation, (boost-)immunization) and as a possible delivery system for IPT in schoolchildren (IPTsc). However, the current evidence on the efficacy and safety of IPTsc is limited and the optimal therapeutic regimen remains controversial. METHODS: A systematic search for studies reporting efficacy and safety of IPT in schoolchildren was conducted using PubMed, Web of Science, Clinicaltrials and WHO/ICTRP database, and abstracts from congresses with the following key words: intermittent, preventive treatment AND malaria OR Plasmodium falciparum AND schoolchildren NOT infant NOT pregnancy. RESULTS: Five studies were identified. Most IPTsc regimes demonstrated substantial protection against malaria parasitaemia, with dihydroartemisinin-piperaquine (DP) given monthly having the highest protective effect (PE) (94 %; 95 % CI 93-96). Contrarily, SP did not provide any PE against parasitaemia. However, no IPT regimen provided a PE above 50 % in regard to anaemia, and highest protection was provided by SP+ amodiaquine (AQ) given four-monthly (50 %; 95 % CI 41-53). The best protection against clinical malaria was observed in children monthly treated with DP (97 %; 95 % CI 87-98). However, there was no protection when the drug was given three-monthly. No severe adverse events were associated with the drugs used for IPTsc. CONCLUSION: IPTsc may reduce the malaria-related burden in schoolchildren. However, more studies assessing efficacy of IPT in particular against malaria-related anaemia and clinical malaria in schoolchildren must be conducted.

Toxoplasmosis among pregnant women：High seroprevalence and risk factors in Kinshasa, Democratic Republic of Congo

Objective:To determine the seroprevalence of toxoplasmosis in pregnant women, as well as the proportion of acutely infected and risk factors in the Democratic Republic of Congo. Methods:Thirty maternities in Kinshasa were randomly selected and women attending antenatal consultation were invited to participate. They were interviewed with a structured questionnaire about known risk factors (age, meat consumption, contact with soil, and presence of cat) and a venous blood sample was taken. Sera were analysed for total immunoglobulins (Ig) by VIDAS Toxo Competition using Enzyme Linked Fluorescent Assay. IgM was determined by VIDIA Toxo IgM and IgG avidity by VIDAS Toxo IgG avidity. Results: A total of 781 women were included. Median age was 28 years old (IQR: 8.5). And 627 women (80.3%; 95%CI: 77.5-83.1) were found to be positive to total Ig and 17 out of 387 (4.4%;95%CI: 2.3-6.4) were positive to IgM. IgG avidity was low for 2 (11.8%) women, intermediate for 2 (11.8%) and high for 13 women (76.4%). There was no statistically significant association between Toxoplasma gondii infection and any risk factors assessed. Conclusion: In Kinshasa, toxoplasmosis endemicity is highly prevalent. One woman out of twenty five had a recent toxoplasmosis infection and 20%were not protected against primo-infection, indicating a need for measures to prevent and control toxoplasmosis during pregnancy.

Toxoplasmosis among pregnant women: high seroprevalence and risk factors in Kinshasa, Democratic Republic of Congo

<p><b>OBJECTIVE</b>To determine the seroprevalence of toxoplasmosis in pregnant women, as well as the proportion of acutely infected and risk factors in the Democratic Republic of Congo.</p><p><b>METHODS</b>Thirty maternities in Kinshasa were randomly selected and women attending antenatal consultation were invited to participate. They were interviewed with a structured questionnaire about known risk factors (age, meat consumption, contact with soil, and presence of cat) and a venous blood sample was taken. Sera were analysed for total immunoglobulins (Ig) by VIDAS Toxo Competition using Enzyme Linked Fluorescent Assay. IgM was determined by VIDIA Toxo IgM and IgG avidity by VIDAS Toxo IgG avidity.</p><p><b>RESULTS</b>A total of 781 women were included. Median age was 28 years old (IQR: 8.5). And 627 women (80.3%; 95% CI: 77.5-83.1) were found to be positive to total Ig and 17 out of 387 (4.4%; 95% CI: 2.3-6.4) were positive to IgM. IgG avidity was low for 2 (11.8%) women, intermediate for 2 (11.8%) and high for 13 women (76.4%). There was no statistically significant association between Toxoplasma gondii infection and any risk factors assessed.</p><p><b>CONCLUSION</b>In Kinshasa, toxoplasmosis endemicity is highly prevalent. One woman out of twenty five had a recent toxoplasmosis infection and 20% were not protected against primo-infection, indicating a need for measures to prevent and control toxoplasmosis during pregnancy.</p>

Diagnostic accuracy of loopamp Trypanosoma brucei detection kit for diagnosis of human African trypanosomiasis in clinical samples.

BACKGROUND: Molecular methods have great potential for sensitive parasite detection in the diagnosis of human African trypanosomiasis (HAT), but the requirements in terms of laboratory infrastructure limit their use to reference centres. A recently developed assay detects the Trypanozoon repetitive insertion mobile element (RIME) DNA under isothermal amplification conditions and has been transformed into a ready-to-use kit format, the Loopamp Trypanosoma brucei. In this study, we have evaluated the diagnostic performance of the Loopamp Trypanosoma brucei assay (hereafter called LAMP) in confirmed T.b. gambiense HAT patients, HAT suspects and healthy endemic controls from the Democratic Republic of the Congo (DRC). METHODOLOGY/PRINCIPAL FINDINGS: 142 T.b. gambiense HAT patients, 111 healthy endemic controls and 97 HAT suspects with unconfirmed status were included in this retrospective evaluation. Reference standard tests were parasite detection in blood, lymph or cerebrospinal fluid. Archived DNA from blood of all study participants was analysed in duplicate with LAMP. Sensitivity of LAMP in parasitologically confirmed cases was 87.3% (95% CI 80.9-91.8%) in the first run and 93.0% (95% CI 87.5-96.1%) in the second run. Specificity in healthy controls was 92.8% (95% CI 86.4-96.3%) in the first run and 96.4% (95% CI 91.1-98.6%) in the second run. Reproducibility was excellent with a kappa value of 0.81. CONCLUSIONS/SIGNIFICANCE: In this laboratory-based study, the Loopamp Trypanosoma brucei Detection Kit showed good diagnostic accuracy and excellent reproducibility. Further studies are needed to assess the feasibility of its routine use for diagnosis of HAT under field conditions.