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Hard-to-reach communities represent Peru's main challenge for malaria elimination, but information about transmission in these areas is scarce. Here, we assessed Plasmodium vivax (Pv) and P. falciparum (Pf) transmission dynamics, resistance markers, and Pf hrp2/3 deletions in Nueva Jerusalén (NJ), a remote, indigenous community in the Peruvian Amazon with high population mobility. We collected samples from November 2019 to May 2020 by active (ACD) and passive case detection (PCD) in NJ. Parasites were identified with microscopy and PCR. Then, we analyzed a representative set of positive-PCR samples (Pv = 68, Pf = 58) using highly-multiplexed deep sequencing assays (AmpliSeq) and compared NJ parasites with ones from other remote Peruvian areas using population genetics indexes. The ACD intervention did not reduce malaria cases in the short term, and persistent malaria transmission was observed (at least one Pv infection was detected in 96% of the study days). In Nueva Jerusalen, the Pv population had modest genetic diversity (He = 0.27). Pf population had lower diversity (He = 0.08) and presented temporal clustering, one of these clusters linked to an outbreak in February 2020. Moreover, Pv and Pf parasites from NJ exhibited variable levels of differentiation (Pv Fst = 0.07-0.52 and Pf Fst = 0.11-0.58) with parasites from other remote areas. No artemisin resistance mutations but chloroquine (57%) and sulfadoxine-pyrimethamine (35-67%) were detected in NJ's Pf parasites. Moreover, pfhrp2/3 gene deletions were common (32-50% of parasites with one or both genes deleted). The persistent Pv transmission and the detection of a Pf outbreak with parasites genetically distinct from the local ones highlight the need for tailored interventions focusing on mobility patterns and imported infections in remote areas to eliminate malaria in the Peruvian Amazon.
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Malária Falciparum , Malária Vivax , Plasmodium falciparum , Plasmodium vivax , Proteínas de Protozoários , Peru/epidemiologia , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Vivax/transmissão , Proteínas de Protozoários/genética , Feminino , Masculino , Criança , Adulto , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Adolescente , Resistência a Medicamentos/genética , Pessoa de Meia-Idade , Povos Indígenas/genética , Adulto Jovem , Pré-Escolar , Genômica/métodos , Variação Genética , Antígenos de Protozoários/genéticaRESUMO
This study explored the experiences of healthcare providers (HCPs) and frontline workers who were involved in an Ebola vaccine trial in the Democratic Republic of the Congo. The researchers interviewed a total of 99 participants (HCPs and frontline workers) living and working in the Boende health district during the period of the study, from February to March 2022. These individuals included a mix of trial participants and non-trial participants (staff of the trial, local health authorities, and head nurses of health centers). In-depth individual interviews, as well as focus group discussions (FGDs), were used to understand interviewees' experiences and perceptions. The data were analyzed to identify the main themes. The findings unveiled a multitude of positive experiences among interviewees/FGD participants. The commitment of the trial investigators to improve the study site and to equip the volunteers with necessary skills and knowledge greatly contributed to a positive trial experience. However, some interviewees felt that the reimbursement for time and travel expenses during their trial visits was insufficient in comparison with their expectations. Additionally, there were expressions of worry about the frequency of blood draws during scheduled trial visits. Our findings emphasize the critical importance of addressing and continuously considering the perspectives and concerns of trial participants before designing and implementing vaccine trials. By actively incorporating their inputs, researchers can mitigate concerns and tailor communication strategies, potentially enhancing the overall success and impact of the vaccine trial.
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Cardiovascular disease (CVD) poses a global health challenge, with modifiable risk factors, notably alcohol consumption, impacting its onset and progression. This review synthesizes evidence on the types and effectiveness of community-based interventions (CBIs) aimed at reducing alcohol consumption for CVD prevention. Electronic databases were systematically searched until October 31, 2019, with updates until February 28, 2023. Given the heterogeneity in outcome measures, we narratively synthesized the effectiveness of CBIs, adhering to the synthesis without meta-analysis (SWiM) guidelines for transparent reporting. For selected homogenous studies, a random-effects meta-analysis was utilized to estimate the effects of CBIs on alcohol consumption. Twenty-two eligible studies were included, with 16 demonstrating that CBIs reduced alcohol consumption compared to controls. Meta-analysis findings revealed reductions in above moderate-level alcohol consumption (pooled odds ratio (OR)=0.50, 95% confidence interval (CI): 0.37, 0.68), number of alcohol drinks per week (standardized mean difference=-0.08, 95% CI: -0.14, -0.03), and increased odds of low-risk drinking (pooled OR=1.99, 95% CI: 1.04, 3.81) compared to the control groups. Multi-component interventions (particularly those combining health education, awareness, and promotion activities) and those interventions with a duration of 12 months or more were notably effective. The beneficial effects of CBIs focusing on achieving a reduction in alcohol consumption showed promising outcomes. Implementing such interventions, especially multicomponent interventions, could play a significant role in mitigating the increasing burden of CVDs. Future studies should also consider employing standardized and validated tools to measure alcohol consumption outcomes to enhance the consistency and comparability of findings.
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OBJECTIVE: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. METHODS: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379). RESULTS: The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, P=0.013), but no differences were observed between the treatment arms (χ2=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, P=0.32). CONCLUSIONS: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.
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Amodiaquina , Antimaláricos , Artemisininas , Combinação de Medicamentos , Resistência a Medicamentos , Malária Falciparum , Plasmodium falciparum , Humanos , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Tanzânia/epidemiologia , Criança , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/parasitologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Resistência a Medicamentos/genética , Masculino , Feminino , Amodiaquina/uso terapêutico , Artemisininas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Quinolinas/uso terapêutico , Pré-Escolar , Proteínas de Protozoários/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Marcadores Genéticos , Variações do Número de Cópias de DNA , PiperazinasRESUMO
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.
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Vacinas contra Ebola , Humanos , Masculino , Feminino , Vacinas contra Ebola/economia , Adulto , República Democrática do Congo , Estudos Longitudinais , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/economia , Política de Saúde , Pessoa de Meia-Idade , Pessoal de SaúdeRESUMO
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 10â781·6 EU/mL (9354·4-12â426·4) for group 1 and 10â746·9 EU/mL (9208·7-12â542·0) 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.
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Anticorpos Antivirais , Vacinas contra Ebola , Ebolavirus , Pessoal de Saúde , Doença pelo Vírus Ebola , Imunização Secundária , Humanos , República Democrática do Congo , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/imunologia , Vacinas contra Ebola/imunologia , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/efeitos adversos , Masculino , Adulto , Feminino , Anticorpos Antivirais/sangue , Ebolavirus/imunologia , Ebolavirus/genética , Pessoa de Meia-Idade , Adulto Jovem , Vacinação/métodosRESUMO
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.
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Vacinas contra Ebola , Doença pelo Vírus Ebola , Humanos , República Democrática do Congo , Vacinas contra Ebola/efeitos adversos , Pessoal de Saúde , Doença pelo Vírus Ebola/prevenção & controle , Consentimento Livre e Esclarecido , Ensaios Clínicos como AssuntoRESUMO
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.
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Vacinas contra Ebola , Ebolavirus , Doença pelo Vírus Ebola , Vacina Antivariólica , Animais , Humanos , República Democrática do Congo , Anticorpos Antivirais , Glicoproteínas , Imunogenicidade da Vacina , Vacinas AtenuadasRESUMO
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.
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Vacinas contra Ebola , Doença pelo Vírus Ebola , Humanos , Comunicação , República Democrática do Congo/epidemiologia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Universidades , Ensaios Clínicos como AssuntoRESUMO
INTRODUCTION: Maternal healthcare utilization, particularly the institutional delivery, is disproportionately low in rural Ethiopia. This study aimed to evaluate the effectiveness of an integrated package of community-based interventions on the improved knowledge of obstetric danger signs, birth preparedness, and institutional delivery services utilization in rural areas of Gamo zone, southern Ethiopia. METHODS: We conducted cluster-randomized controlled trial (NCT05385380) from 2019 to 2021 at the Arba Minch Health and Demographic Surveillance System site. We randomly assigned the 10 kebele clusters to intervention and control arm. We used a package of interventions, which included providing information on safe motherhood via video and/or audio with a birth preparedness card for pregnant women, training for community volunteers and health extension workers, and improving maternity waiting home services. Women in the control arm received routine services only. We used generalized mixed-effects logistic regression models to evaluate the effectiveness of the intervention on the outcome variables. RESULTS: The study enrolled 727 pregnant women across the 10 clusters, with a 617 (84.9%) successful follow-up rate. The proportion of institutional delivery in the intervention arm was increased by 16.1% from 36.4% (174/478) at the baseline to 52.5% (224/427) at the endline (Adjusted odds ratio [AOR] for McNemar's Test = 1.5; 95% confidence interval [CI]: 1.1 to 2; p < 0.001). In the control arm, however, there was a 10.3% fall in the proportion of institutional delivery (from 164/249 to 105/190). Pregnant women who received the intervention were significantly more likely to give birth in a health institution than those who did not (AOR 2.8; 95% CI: 1.2, 6.4). CONCLUSION: The study demonstrates that an integrated community-based intervention package that included video-based storytelling and upgrading maternity waiting homes increased institutional delivery care utilization among rural women. We recommend that audio-visual storytelling, starting during pregnancy and continuing postpartum, be incorporated into routine maternal healthcare services to address access to care inequalities in rural settings. TRIAL REGISTRATION: The study protocol was registered in the clinicaltrials.gov with registry number NCT05385380.
Many women in developing nations, including Ethiopia, are dying due to problems related to pregnancy and childbirth. One of the interventions to prevent maternal illness and deaths is promoting and ensuring the timely use of maternal health care services. This study aimed to evaluate the effectiveness of an integrated package of community-based interventions on the improved institutional birth rate in rural Ethiopia. We conducted a trial at the Arba Minch HDSS site. The package provided information on safe motherhood via videos and audiocassettes for pregnant women, a birth preparedness card for women, community volunteers and extension workers training, and maternity waiting home services upgrading. In the control arm, women received routine services only. From the 10 Arba Minch HDSS kebele clusters, six kebele clusters were randomly assigned to the intervention and an additional four were assigned to the control. Different statistical techniques were used to evaluate the effectiveness of the intervention on the institutional birth rate. At the baseline, 727 pregnant women had enrolled across all 10 clusters, with a 617 (84.9%) successful follow-up rate. The intervention arm had a higher proportion of institutional birth (224/427 [52.5%]) at the endline than the baseline (174/478 [36.4%). Furthermore, the study showed a significant association between intervention status and institutional birth rate. Therefore, stimulating demand for existing services to ensure the timely use of care can improve maternal health service utilization, particularly the institutional birth rate.
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Serviços de Saúde Materna , Cuidado Pré-Natal , Feminino , Gravidez , Humanos , Etiópia , Cuidado Pré-Natal/métodos , Gestantes , Aceitação pelo Paciente de Cuidados de Saúde , Parto ObstétricoRESUMO
Pregnant women are generally excluded from clinical research over safety concerns. However, demands to include them in clinical vaccine development have intensified after recent COVID-19, Ebola, and Lassa fever outbreaks given the disproportionate effect of these diseases on pregnant women and/or their foetuses. Numerous studies highlighted the scarcity of safety data for therapeutic interventions in pregnant women. Nevertheless, only a small number have assessed the number of vaccine trials including this population. Therefore, we searched for phase 3 and 4 vaccine clinical trials in healthy populations registered between 2018 and 2023 in clinicaltrials.gov and the International Clinical Trial Registry Platform. Out of 400 registered vaccine trials matching our inclusion criteria, 217 (54 %) were industry-sponsored, and 222 (56 %) had COVID-19 as a target. We found 22 studies (6 %) that either were designed for pregnant women or included them as part of a larger population. Out of these 22 trials, 13 were designed specifically for pregnant women; seven of these were maternal vaccines aiming at protecting the foetus, namely pertussis (3), Respiratory Syncytial Virus (RSV) (3), and meningitis plus tetanus (1) vaccines, and six others targeted either flu (3), COVID-19 (2) or Ebola (1). Only the RSV and Ebola vaccine trials were industry-sponsored. We also found that nine studies targeting the general population included pregnant women. These focused on COVID-19 (3), flu (2), COVID-19 + flu (2), Ebola (1), and Hepatitis B (1). None of these studies was industry-sponsored. Our findings show that a gap still exists in terms of pregnant women's inclusion in vaccine trials. Such a gap needs to be tackled urgently to minimise the devastating effects that a future infectious disease outbreak could have on this population. This study can inform future demands for increased inclusion, especially in industry-sponsored trials, as it provides an overview of the current vaccine trials scene.
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COVID-19 , Vacinas contra Ebola , Doença pelo Vírus Ebola , Complicações Infecciosas na Gravidez , Vírus Sincicial Respiratório Humano , Humanos , Gravidez , Feminino , Gestantes , Complicações Infecciosas na Gravidez/prevenção & controle , COVID-19/prevenção & controleRESUMO
Despite continuous efforts to control schistosomiasis (SCH) in the Democratic Republic of the Congo (DRC), it still poses a significant challenge. In order to enhance control measures, additional research is necessary. This study documents the burden of SCH infection and its predictors in a rural area of the DRC. We conducted a household cross-sectional study from June to August 2021 among 480 school-aged children (SAC) aged 5-15 years living in a rural area of Kisangi, in the southwest DRC. We collected and examined stool, urine, and blood samples of each child. Additionally, we obtained data on anthropometry, socio-demographics, household information, and individual water contact behaviors. The overall prevalence of SCH infection was 55.8% (95% CI: 51.4-60.3), with prevalences of 41% (95% CI: 36.6-45.5), 36.3% (95% CI: 31.9-40.6), and 38.4% (95% CI: 32.6-44.3) for S. haematobium and S. mansoni infections and both infections, respectively. Among those with SCH infection, most had a light (67.5%) or heavy (51.7%) infection intensity. The geometric mean egg count was 16.6 EP 10 mL (95% CI: 12.9-21.3) for S. haematobium and 390.2 EPG (95% CI: 300.2-507.3) for S. mansoni. However, age (10 years and above (aOR: 2.1; 95% CI: 1.5-3.1; p < 0.001)) was an independent risk factor for SCH infection. The overall prevalence of malaria infection was 16.9% (95% CI: 13.5-20.2), that of stunting was 28.7% (95% CI: 24.7-32.8), that of underweight was 17.1% (95% CI: 12.8-21.4), and that of thinness was 7.1% (95% CI: 4.8-9.4). Anemia was prevalent at 49.4% (95% CI: 44.9-5), and the median Hb level of all participants was 11.6 g/dL (IQR: 10.5-12.6 g/dL). Anemia was strongly associated with SCH infection (aOR: 3.4; 95% CI: 2.3-5.1; p < 0.001) yet there was no association with the risk for malaria infection (aOR: 1.0; 95% CI: 0.6-1.8; p = 0.563). In addition, the risk of anemia increased with heavy infection intensities (p < 0.026 and p < 0.013 for S. haematobium and S. mansoni, respectively). However, stunting had a protective factor for anemia (aOR: 0.3; 95% CI: 0.2-0.4; p < 0.001). To conclude, SCH infection was widespread among the SAC and strongly linked to anemia. These results provide evidence of the hyperendemicity of infection in the study area, which requires preventative measures such as chemotherapy to reduce the schistosomiasis-associated morbidity, and micronutrient supplements to avoid anemia.
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BACKGROUND: Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI). METHODS: We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted. RESULTS: The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45-1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51-2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80). CONCLUSION: Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination.
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Vacinas Antimaláricas , Humanos , Animais , Vacinas Antimaláricas/uso terapêutico , Monócitos , Biomarcadores , Linfócitos , Esporozoítos , VacinaçãoRESUMO
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.
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Antígenos de Grupos Sanguíneos , Vacinas contra Ebola , Ebolavirus , Doença pelo Vírus Ebola , Animais , Humanos , República Democrática do Congo , Estudos Soroepidemiológicos , Pessoal de SaúdeRESUMO
BACKGROUND: School-aged children (SAC) have an increased risk to contract malaria and play a major role in its transmission dynamics. However, their malaria prevention experience is poor. Thus, the effect of malaria prevention education (MPE) on bed net utilization, treatment seeking from a health facility and cumulative incidence of malaria was evaluated in Southern Ethiopia. METHODS: A two arm cluster randomized controlled trial was conducted by recruiting 2038 SAC from 32 schools. Structured questionnaire was used to collect data on socio-demographic, economic, bed net ownership, bed net utilization, whether the participated child suffered from malaria and has got treatment from a health facility. Generalized mixed effect logistic regression using school as random variable was used to assess the effect of the intervention on the outcome variables. RESULTS: The ownership of bed net in households of the control and intervention schools was similar respectively with 84.6 and 88.6% (Crude Odds Ratio (COR): 1.5; 95%CI: 0.5-4.8). The percentage of SAC slept under the bed net the night before the survey was also similar (55.1% versus 54.0%); COR:1.04; 95%CI: 0.5-2.4). Bed net utilization was affected by household size to the bed net ratio ≤ 2 (Adjusted Odds Ratio (AOR) = 1.6; 95%CI:1.3-2.1), bed net utilization at baseline of the study (AOR = 2.3; 95%CI:1.5-3.6), and history of malaria attack in the last twelve months (AOR = 1.3; 95%CI:1.01-1.8). Reported cumulative incidence of malaria and treatment seeking from a health facility by SAC was similar between intervention and control arms: -2.1% (COR = 0.8; 95%CI: 0.5-1.5) and 9.6% (COR = 1.4; 95%CI: 0.4-4.3) respectively. The reported incidence of malaria was affected by altitude (AOR = 0.5; 95%CI: 0.3-0.8), low and medium wealth index (AOR = 0.7; 95%CI: 0.5-0.96 and AOR = 0.7; 95%CI: 0.5-0.98), adequate bed net number for household members (AOR = 0.7; 95%CI:0.5-0.9) and bed net utilization (AOR = 1.3; 95%CI:1.1-1.8). CONCLUSIONS: MPE had no significant effect on the use of malaria prevention measures considered, treatment seeking from a health facility and reported cumulative incidence of malaria though bed net use was associated with malaria incidence. Before organizing any health education program, sustainable implementation efforts have to be warranted especially in SAC, a neglected but relevant vulnerable and reservoirs. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202001837195738, registered 21/01/2020.
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Mosquiteiros Tratados com Inseticida , Malária , Humanos , Criança , Incidência , Etiópia/epidemiologia , Escolaridade , Malária/epidemiologia , Malária/prevenção & controleRESUMO
Controlled human malaria infection (CHMI) studies, i.e. the deliberate infection of healthy volunteers with malaria parasites to study immune response and/or test drug or vaccine efficacy, are increasingly being conducted in malaria endemic countries, including in sub-Saharan Africa. However, there have been few studies on the perceptions and acceptability of CHMI by the local communities. This qualitative study assessed the perception and acceptability of such studies in The Gambia following the first CHMI study conducted in the country in March-May 2018. Data were collected through non-participant observation, in-depth interviews and focus group discussions and analyzed using NVivo 12 software with an inductive-deductive approach. Sixty-seven participants were involved, including volunteers enrolled in the CHMI, community stakeholders and members of the Gambian Ethics Committee. Respondents expressed a positive view about CHMI. Key motivating factors for participation were the financial compensation, comprehensive health checks, and willingness to support malaria research. Risks associated with participation were considered low. Concerns raised included the frequency of bleeding and the blood volume collected.
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Malária Falciparum , Malária , Humanos , Gâmbia , Malária/prevenção & controle , Pesquisa Qualitativa , Grupos Focais , Malária Falciparum/parasitologiaRESUMO
OBJECTIVE: We aimed to synthesise available evidence on the effects of community-based interventions in improving various dietary outcome measures. DESIGN: Systematic review and meta-analysis. SETTING: We searched databases including Medline, EMBASE, PSYCINFO, CINAHL and the Cochrane registry for studies reported between January 2000 and June 2022. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tools for each study type. For some of the outcomes, we pooled the effect size using a random-effects meta-analysis. PARTICIPANTS: A total of fifty-one studies, thirty-three randomised and eighteen non-randomised, involving 100 746 participants were included. RESULTS: Overall, thirty-seven studies found a statistically significant difference in at least one dietary outcome measure favouring the intervention group, whereas fourteen studies found no statistically significant difference. Our meta-analyses indicated that, compared with controls, interventions were effective in decreasing daily energy intake (MJ/d) (mean difference (MD): -0·25; 95 % CI: -0·37, -0·14), fat % of energy (MD: -1·01; 95 % CI: -1·76, -0·25) and saturated fat % of energy (MD: -1·54; 95 % CI: -2·01, -1·07). Furthermore, the interventions were effective in improving fibre intake (g/d) (MD: 1·08; 95 % CI: 0·39, 1·77). Effective interventions use various strategies including tailored individual lifestyle coaching, health education, health promotion activities, community engagement activities and/or structural changes. CONCLUSION: This review shows the potential of improving dietary patterns through community-based CVD preventive interventions. Thus, development and implementation of context-specific preventive interventions could help to minimise dietary risk factors, which in turn decrease morbidity and mortality due to CVD and other non-communicable diseases.
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Doenças Cardiovasculares , Dieta , Humanos , Promoção da Saúde , Fatores de Risco , Estilo de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Malaria morbidity and mortality increase in the Democratic Republic of the Congo (DRC) may be the consequence of the low utilization rate of long-lasting insecticidal nets (LLINs) resulting from poor compliance due to adverse events (AEs). This study aimed at determining the prevalence and predictors of AEs following the mass distribution of LLINs in the Kisantu Health Zone (KHZ), a high malaria-endemic region in the DRC. METHODS: A community-based cross-sectional study embedded was conducted within a randomized controlled trial (RCT) after the mass distribution of LLINs in 30 villages located in DRC KHZ. A three-stage sampling method was used without replacement to select 1790 children. Data was collected on adverse events (AEs) using a reporting form and information on demographics, nutritional status, and house characteristics. This was done using a structured questionnaire administered to household heads. Logistic regression models were used to identify predictors of AEs following the mass distribution of LLINs. RESULT: In a total of 1790 children enrolled, 17.8% (95% CI 16.1-19.7) experienced AEs. The most common AEs were respiratory-related (61%). Around 60% of AEs occurred within 24 h of use, and 51% were resolved without treatment. Sleeping under deltamethrin LLINs (Adjusted OR, 95% CI 5.5 [3.8-8.0]) and zinc roofing (Adjusted OR, 95% CI 1.98 [1.1-3.57]) were associated with the risk of reporting an AE following the mass distribution of LLINs. CONCLUSION: Approximately 1 out of 5 children had an AE within 24 h following LLIN use. These adverse events were often respiratory-related. LLINs and roofing types were associated with a higher risk of reporting AEs. However, further research using a robust study design is needed to confirm these findings. Future studies should design and implement interventions aiming to reduce AEs and improve compliance with LLINs.
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Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Criança , Humanos , Inseticidas/efeitos adversos , República Democrática do Congo/epidemiologia , Prevalência , Estudos Transversais , Malária/prevenção & controle , Malária/epidemiologia , Controle de Mosquitos/métodosRESUMO
Molecular surveillance for malaria has great potential to support national malaria control programs (NMCPs). To bridge the gap between research and implementation, several applications (use cases) have been identified to align research, technology development, and public health efforts. For implementation at NMCPs, there is an urgent need for feasible and cost-effective tools. We designed a new highly multiplexed deep sequencing assay (Pf AmpliSeq), which is compatible with benchtop sequencers, that allows high-accuracy sequencing with higher coverage and lower cost than whole-genome sequencing (WGS), targeting genomic regions of interest. The novelty of the assay is its high number of targets multiplexed into one easy workflow, combining population genetic markers with 13 nearly full-length resistance genes, which is applicable for many different use cases. We provide the first proof of principle for hrp2 and hrp3 deletion detection using amplicon sequencing. Initial sequence data processing can be performed automatically, and subsequent variant analysis requires minimal bioinformatic skills using any tabulated data analysis program. The assay was validated using a retrospective sample collection (n = 254) from the Peruvian Amazon between 2003 and 2018. By combining phenotypic markers and a within-country 28-single-nucleotide-polymorphism (SNP) barcode, we were able to distinguish different lineages with multiple resistance haplotypes (in dhfr, dhps, crt and mdr1) and hrp2 and hrp3 deletions, which have been increasing in recent years. We found no evidence to suggest the emergence of artemisinin (ART) resistance in Peru. These findings indicate a parasite population that is under drug pressure but is susceptible to current antimalarials and demonstrate the added value of a highly multiplexed molecular tool to inform malaria strategies and surveillance systems. IMPORTANCE While the power of next-generation sequencing technologies to inform and guide malaria control programs has become broadly recognized, the integration of genomic data for operational incorporation into malaria surveillance remains a challenge in most countries where malaria is endemic. The main obstacles include limited infrastructure, limited access to high-throughput sequencing facilities, and the need for local capacity to run an in-country analysis of genomes at a large-enough scale to be informative for surveillance. In addition, there is a lack of standardized laboratory protocols and automated analysis pipelines to generate reproducible and timely results useful for relevant stakeholders. With our standardized laboratory and bioinformatic workflow, malaria genetic surveillance data can be readily generated by surveillance researchers and malaria control programs in countries of endemicity, increasing ownership and ensuring timely results for informed decision- and policy-making.
RESUMO
BACKGROUND: Despite efforts to make maternal health care services available in rural Ethiopia, utilisation status remains low. Therefore, this study aimed to assess maternal health care services' status and determinants in rural Ethiopia. METHODS: The study used quasi-experimental pre- and post-comparison baseline data. A pretested, semi-structured, interviewer-administered questionnaire was used to collect data. A multilevel, mixed-effects logistic regression was used to identify individual and communal level factors associated with utilisation of antenatal care (ANC), skilled birth attendance (SBA), and postnatal care (PNC). The adjusted odds ratio (AOR) and corresponding 95% confidence intervals (CI) were estimated with a p-value of less than 0.05, indicating statistical significance. RESULTS: Seven hundred and twenty-seven pregnant women participated, with a response rate of 99.3%. Four hundred and sixty-one (63.4%) of the women visited ANC services, while 46.5% (CI: 42-50%) of births were attended by SBA, and 33.4% (CI: 30-36%) had received PNC. Women who reported that their pregnancy was planned (aOR = 3.9; 95% CI: 1.8-8.3) and were aware of pregnancy danger signs (aOR = 6.8; 95% CI: 3.8-12) had a higher likelihood of attending ANC services. Among the cluster-level factors, women who lived in lowlands (aOR = 4.1; 95% CI: 1.1-14) and had easy access to transportation (aOR = 1.9; 95% CI: 1.1-3.7) had higher odds of visiting ANC services. Moreover, women who were employed (aOR = 3.1; 95% CI: 1.3-7.3) and attended ANC (aOR = 3.3; 95% CI: 1.8-5.9) were more likely to have SBA at delivery. The likelihood of being attended by SBA during delivery was positively correlated with shorter travel distances (aOR = 2.9; 95% CI: 1.4-5.8) and ease of access to transportation (aOR = 10; 95% CI: 3.6-29) to the closest healthcare facilities. Being a midland resident (aOR = 4.7; 95% CI: 1.7-13) and having SBA during delivery (aOR = 2.1; 95% CI: 1.2-3.50) increased the likelihood of attending PNC service. CONCLUSIONS: Overall, maternal health service utilisation is low in the study area compared with the recommended standards. Women's educational status, awareness of danger signs, and pregnancy planning from individual-level factors and being a lowland resident, short travel distance to health facilities from the cluster-level factors play a crucial role in utilising maternal health care services. Working on women's empowerment, promotion of contraceptive methods to avoid unintended pregnancy, and improving access to health care services, particularly in highland areas, are recommended to improve maternal health service utilisation.