Publications by authors named "Aaron M Samuels"

Background: Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both, are important for developing improved vaccines. We estimated influenza infection incidence, and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design.

Methods: We conducted a prospective cohort study among children aged 6-23 months from May-October 2022.

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  • The study evaluated the effectiveness of two COVID-19 vaccines (Pfizer BNT162b2 and Johnson & Johnson Ad26.COV2.S) in preventing hospitalizations in South African adults during different SARS-CoV-2 variants.
  • It included 925 cases (hospitalized) and 1890 controls (not hospitalized), analyzing their vaccination status and disease outcomes from June 2021 to March 2022.
  • Results showed that BNT162b2 had high effectiveness against hospitalizations during the Delta variant wave, particularly in older and HIV-uninfected adults, while the effectiveness of Ad26.COV2.S was inconclusive.
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  • Acute febrile illness (AFI) is frequently misattributed to malaria in Sub-Saharan Africa, but a variety of pathogens can cause fever, emphasizing the need for better understanding and management of AFI.
  • A study across four sites in Kenya from June 2017 to March 2019 enrolled over 3,200 AFI cases, primarily among children under 5, finding that 4.3% resulted in hospital fatalities and that many cases had undetermined causes.
  • Identification of pathogens revealed malaria (Plasmodium) as the most common, while HIV and chikungunya were also detected; the results highlight the importance of improved diagnostics to address both malaria and non-malarial fever causes effectively.
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  • The RTS,S/AS01 malaria vaccine was tested for its effectiveness in a study involving 1,500 children aged 5-17 months in Ghana and Kenya, focusing on different dosing regimens.
  • Four different groups received the vaccine in varying full and fractional doses, while a control group got a rabies vaccine.
  • Results showed all RTS,S/AS01 regimens provided similar vaccine efficacy (25-43%) against new malaria infections, significantly reducing the number of infections over a 20-month follow-up period.
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  • - The study aimed to identify risk factors for severe COVID-19 hospitalization among children aged 18 and younger by analyzing data from surveillance sites between April 2020 and March 2022
  • - Among 4688 participants, certain risk factors were found: children under 6 months old, those with underlying medical conditions, infections with specific COVID-19 variants, and co-infection with respiratory syncytial virus (RSV) were more likely to be hospitalized
  • - The findings highlight the importance of age and underlying health issues in assessing the risk of severe respiratory illnesses due to COVID-19 in children, suggesting that ongoing surveillance can effectively monitor these risks.
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  • The RTS,S/AS01 malaria vaccine was launched in Ghana, Kenya, and Malawi in 2019 to evaluate its feasibility, impact, and safety after concerns about potential health risks emerged during earlier trials.
  • A prospective evaluation involved randomly assigning 158 geographical clusters to receive the vaccine either early or later, monitoring various health outcomes in children over four years.
  • Key outcomes included overall mortality, severe malaria rates, hospital admissions for meningitis, and vaccine coverage, with a specific focus on monitoring potential safety issues, particularly among girls.
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Background: The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.

Methods: In total, 1500 children aged 5-17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine.

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Background: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality.

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  • The impact of asymptomatic infections on influenza transmission was unclear before COVID-19, but the pandemic has raised new questions about their significance.
  • Experts are now reevaluating the importance of these asymptomatic infections in transmitting influenza, given the established role of asymptomatic individuals in spreading COVID-19.
  • The text highlights current knowledge on the frequency and contribution of asymptomatic influenza infections to transmission, while suggesting areas for further research to fill existing gaps.
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Background: The only licensed malaria vaccine, RTS,S/AS01 , confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy (VE).

Methods: 1,500 children aged 5-17 months were randomized to receive four different RTS,S/AS01 regimens or a rabies control vaccine in a phase 2b clinical trial in Ghana and Kenya.

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Limited evidence suggests that children in sub-Saharan Africa hospitalized with all-cause severe anemia or severe acute malnutrition (SAM) are at high risk of dying in the first few months after discharge. We aimed to compare the risks of post-discharge mortality by health condition among hospitalized children in an area with high malaria transmission in western Kenya. We conducted a retrospective cohort study among recently discharged children aged < 5 years using mortality data from a health and demographic surveillance system that included household and pediatric in-hospital surveillance.

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Background: Entomological surveillance is traditionally conducted by supervised teams of trained technicians. However, it is expensive and limiting in the number of sites visited. Surveillance through community-based collectors (CBC) may be more cost-effective and sustainable for longitudinal entomological monitoring.

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  • Rapid diagnostic tests (RDTs) are crucial for detecting malaria, especially in pregnancy, and a new highly sensitive rapid diagnostic test (HS-RDT) shows promise for improving diagnosis and outcomes in malaria-endemic regions.
  • A review of thirteen studies comparing HS-RDT with conventional RDT (co-RDT) and molecular methods found varying sensitivity rates for both tests, with HS-RDT generally performing better in detecting low parasite densities.
  • Despite its higher analytical sensitivity, the clinical advantages of HS-RDT over co-RDT were marginal and not statistically significant, indicating a need for further research to fully assess the benefits of RDT improvements.
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  • Attractive targeted sugar baits (ATSBs) utilize the natural sugar-feeding habits of mosquitoes, particularly Anopheles species, as a method for vector control.
  • A study conducted in western Kenya found that 15.7% of the collected mosquitoes had fed on natural sugars, with males generally having a higher sugar-feeding rate than females, especially in the Anopheles funestus species.
  • The results indicate that mosquitoes consistently seek sugar meals at different life stages and locations, highlighting the potential for using ATSBs in mosquito population management.
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  • Detection of malaria in RDT-negative samples can be done using pooled testing with molecular tools, which saves costs compared to individual tests.
  • A study in western Kenya tested 4670 samples and found varying prevalence rates of subpatent malaria across different testing strategies, highlighting the importance of statistical adjustments for accuracy.
  • The one-step pooled testing approach not only represents a feasible alternative but also significantly reduced testing costs by 52% compared to individual sample testing.
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  • * A systematic review and meta-analysis of 20 studies involving over 6,400 participants assessed the impact of primaquine on hemoglobin levels and adverse effects, focusing on those with and without G6PD deficiency.
  • * Results showed no significant hemoglobin reduction in G6PD-normal individuals, but a notable drop in G6PD-deficient patients; serious adverse events were rare, with only one report of a blood transfusion and no deaths linked to primaquine.
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Background: Over the last two decades, the scale-up of vector control and changes in the first-line anti-malarial, from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP) and then to artemether-lumefantrine (AL), have resulted in significant decreases in malaria burden in western Kenya. This study evaluated the long-term effects of control interventions on molecular markers of Plasmodium falciparum drug resistance using parasites obtained from humans and mosquitoes at discrete time points.

Methods: Dried blood spot samples collected in 2012 and 2017 community surveys in Asembo, Kenya were genotyped by Sanger sequencing for markers associated with resistance to SP (Pfdhfr, Pfdhps), CQ, AQ, lumefantrine (Pfcrt, Pfmdr1) and artemisinin (Pfk13).

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  • * A study conducted in Siaya County, Kenya, enrolled 340 children with uncomplicated P. falciparum malaria, comparing the efficacy of two treatments: artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP).
  • * Results showed high efficacy for both treatments, but AL had significantly more reinfections compared to DP, indicating that AL's effectiveness may be decreasing over time, necessitating ongoing monitoring and research.
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Background: Screen-and-treat strategies with sensitive diagnostic tests may reduce malaria-associated adverse pregnancy outcomes. We conducted a diagnostic accuracy study to evaluate new point-of-care tests to screen pregnant women for malaria at their first antenatal visit in western Kenya.

Methods: Consecutively women were tested for Plasmodium infection by expert microscopy, conventional rapid diagnostic test (cRDT), ultra sensitive RDT (usRDT), and loop-mediated isothermal amplification (LAMP).

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  • The study investigates the efficacy of different fractional-dose regimens of the RTS,S/AS01 malaria vaccine in children, focusing on natural exposure rather than laboratory settings.
  • Conducted across sites in Ghana and Kenya, the trial involved children aged 5-17 months who had received basic vaccinations and compared their responses to various dosing schedules.
  • The primary goal is to evaluate the effectiveness and safety of these fractional doses compared to full doses over a period of 12 months, contributing valuable data to malaria vaccine development.
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Background: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa.

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Background: Spatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round.

Methods: This trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial.

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Histidine-rich protein 2 (HRP2)-based rapid diagnostic tests detect Plasmodium falciparum malaria and are used throughout sub-Saharan Africa. However, deletions in the pfhrp2 and related pfhrp3 (pfhrp2/3) genes threaten use of these tests. Therapeutic efficacy studies (TESs) enroll persons with symptomatic P.

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The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination.

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The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018.

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