Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Diagnostic efficacy of lung ultrasound in cardiogenic pulmonary edema: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the diagnostic efficacy of lung ultrasound (LUS) in cardiogenic pulmonary edema. MATERIALS AND METHODS: An electronic search of databases, including MEDLINE, Embase, PubMed, and Web of Science, was performed to collect clinical studies on ultrasound diagnosis of cardiogenic pulmonary edema from inception to 23 March 2023. The number of patients with true-positive, true-negative, false-positive, and false-negative cardiogenic pulmonary edema diagnosed by LUS was collected, and the R package was used to analyze the diagnostic efficacy of LUS. RESULTS: Nine pieces of literature were finally included with 2,097 participants, including 1,047 patients with cardiogenic heart failure. Across the nine included papers, the pooled sensitivity of LUS in the included studies was 0.92 (95% CI: 0.84, 0.97) with a maximum sensitivity of 0.99 (95% CI: 0.96 to 1.00) and a minimum of 0.59 (95% CI: 0.50, 0.68). The pooled specificity of the included studies was 0.87 (95% CI: 0. 82, 0.91) with a maximum specificity of 0.93 (95% CI: 0.90-0.95) and a minimum of 0.80 (95% CI: 0.67, 0.89). The pooled AUC was 0.93 (95% CI: 0.84 to 0.97), suggesting a high diagnostic value of LUS in cardiogenic pulmonary edema. CONCLUSIONS: Lung ultrasound offers a good diagnostic efficacy for cardiogenic pulmonary edema. Further standardization of the examination method is required to provide a reference for the clinical use of LUS.

High-precision cavity-enhanced spectroscopy for studying the H2-Ar collisions and interactions.

Information about molecular collisions is encoded in the shapes of collision-perturbed molecular resonances. This connection between molecular interactions and line shapes is most clearly seen in simple systems, such as the molecular hydrogen perturbed by a noble gas atom. We study the H2-Ar system by means of highly accurate absorption spectroscopy and ab initio calculations. On the one hand, we use the cavity-ring-down-spectroscopy technique to record the shapes of the S(1) 3-0 line of molecular hydrogen perturbed by argon. On the other hand, we simulate the shapes of this line using ab initio quantum-scattering calculations performed on our accurate H2-Ar potential energy surface (PES). In order to validate the PES and the methodology of quantum-scattering calculations separately from the model of velocity-changing collisions, we measured the spectra in experimental conditions in which the influence of the latter is relatively minor. In these conditions, our theoretical collision-perturbed line shapes reproduce the raw experimental spectra at the percent level. However, the collisional shift, δ0, differs from the experimental value by 20%. Compared to other line-shape parameters, collisional shift displays much higher sensitivity to various technical aspects of the computational methodology. We identify the contributors to this large error and find the inaccuracies of the PES to be the dominant factor. With regard to the quantum scattering methodology, we demonstrate that treating the centrifugal distortion in a simple, approximate manner is sufficient to obtain the percent-level accuracy of collisional spectra.

Neoadjuvant immunotherapy for colorectal cancer / 中华胃肠外科杂志

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.

The Nigerian Dentist: Emerging Trends in Caries Management.

BACKGROUND: Fundamental to effective caries management, are measures that eliminate caries risk factors and increase caries protective factors. These include the use of appropriate and effective caries assessment, diagnostic and teaching methods. OBJECTIVES: To assess the use of current caries management protocols and teaching methods/techniques among Nigerian Dentists. METHODS: A pre-tested self-administered questionnaire was used. Only dentists of Nigerian descent and practicing in Nigeria were assessed. The questionnaire inquired about diagnostic tools, assessment and teaching methods used by the Dentists in caries management. RESULTS: More than half of the participants reported use of visual (86.3%), tactile method (76.2%) and periapical radiographs (66.2%) at all times for caries diagnosis. More than three quarters had never used electrical conductance, fibre-optic, CAMBRA, ICDAS, laser fluorescence or bacteria count in caries assessment and diagnosis. Among the 38.4% of the respondents who taught courses on cariology, didactic method and demonstration were the commonest methods used, while use of games was the least used. Didactic method was used more by those that had practiced for 10 years and more. This relationship was statistically significant (p= 0.05). CONCLUSION: Majority of Nigerian Dentists still depend solely on traditional methods of teaching, assessment and diagnosis of dental caries. Modern caries assessment, diagnostic techniques and teaching methods are needed to improve caries management in order to promote early treatment, which is often preventive.

CONTEXTE: Les mesures visant à éliminer les facteurs de risque de carie et à augmenter les facteurs de protection de la carie sont fondamentales pour une gestion efficace de la carie. Ces mesures comprennent l'utilisation de méthodes appropriées et efficaces d'évaluation, de diagnostic et d'enseignement des caries. OBJECTIFS: Évaluer l'utilisation des protocoles actuels de gestion des caries et des méthodes/techniques d'enseignement chez les dentistes nigérians. MÉTHODES: Un questionnaire autoadministré pré-testé a été utilisé. Seuls les dentistes d'origine nigériane et exerçant au Nigeria ont été évalués. Le questionnaire portait sur les outils de diagnostic, l'évaluation et les méthodes d'enseignement utilisés par les dentistes pour la gestion des caries. RÉSULTATS: Plus de la moitié des participants ont déclaré utiliser la méthode visuelle (86,3 %), la méthode tactile (76,2 %) et les radiographies périapicales (66,2 %) à tout moment pour le diagnostic des caries. Plus des trois quarts n'avaient jamais utilisé la conductivité électrique, la fibre optique, la CAMBRA, l'ICDAS, la fluorescence laser ou la numération bactérienne pour évaluer et diagnostiquer les caries. Parmi les 38,4 % des personnes interrogées ayant donné des cours de cariologie, la méthode didactique et la démonstration étaient les méthodes les plus utilisées, tandis que l'utilisation de jeux était la moins utilisée. La méthode didactique était plus utilisée par ceux qui avaient pratiqué pendant 10 ans et plus. Cette relation était statistiquement significative (p= 0,05). CONCLUSION: La majorité des dentistes nigérians dépendent encore uniquement des méthodes traditionnelles d'enseignement, d'évaluation et de diagnostic des caries dentaires. Des techniques modernes d'évaluation et de diagnostic des caries ainsi que des méthodes d'enseignement sont nécessaires pour améliorer la gestion des caries afin de promouvoir un traitement précoce, qui est souvent préventif. Mots clés: Gestion des caries, cariologie, dentistes nigérians.

Fano-like Resonance due to Interference with Distant Transitions.

Narrow optical resonances of atoms or molecules have immense significance in various precision measurements, such as testing fundamental physics and the generation of primary frequency standards. In these studies, accurate transition centers derived from fitting the measured spectra are demanded, which critically rely on the knowledge of spectral line profiles. Here, we propose a new mechanism of Fano-like resonance induced by distant discrete levels and experimentally verify it with Doppler-free spectroscopy of vibration-rotational transitions of CO_{2}. The observed spectrum has an asymmetric profile and its amplitude increases quadratically with the probe laser power. Our results facilitate a broad range of topics based on narrow transitions.

Cavity-enhanced saturated absorption spectroscopy of the (30012) - (00001) band of 12C16O2.

The (30012) ← (00001) band of 12C16O2 in the 1.6 µm region is used for satellite observation of carbon dioxide in the Earth's atmosphere. Here, we report a Doppler-free spectroscopy study of this band with comb-locked wavelength-modulated cavity-enhanced absorption spectroscopy. Frequencies of 18 transitions with the rotational quantum numbers up to 42 were determined with sub-kHz accuracy, corresponding to a fractional uncertainty at the 10-12 level. With this precision, we revealed an anomalous decrease of the line shift and an increase of the line broadening for the Lamb dips of CO2 in the low-pressure regime compared to values obtained from Doppler-limited spectra at higher pressures.

The MU Study of Seropositivity and Risk for SARS-CoV-2 and COVID-19: Crucial Behavioral and Immunological Data from Midwestern College Students

ObjectiveWe describe our Fall 2020 study of college students COVID-19 related behaviors, attitudes, and antibody test results. ParticipantsThe study included 1,446 randomly selected and self-enrolled undergraduate and graduate students from a midwestern university. MethodsAn online survey was distributed to a sample of students, between September and December 2020. A sub-group also participated in a SARS-CoV-2 antibody blood draw. ResultsNearly half of students reported a prior COVID-19 test with 22% indicating a positive test, which represents an 11% positivity rate across all student participants. Of those who participated in antibody testing, 15.1% tested positive for SARS-CoV-2 antibodies. Seventy-seven percent of participants said they would get vaccinated. One-third of students reported moderate to severe generalized anxiety disorder and 13% reported moderate to severe depression. ConclusionsThis study informed campus decisions in Fall 2020. The importance of effective public health messaging on campus should continue in the future.

Comb-locked cavity-assisted double-resonance molecular spectroscopy based on diode lasers.

Interactions between a molecule and two or more laser fields are of great interest in various studies, but weak and highly overlapping transitions hinder precision measurements. We present the method of comb-locked cavity-assisted double resonance spectroscopy based on narrow-linewidth continuous-wave lasers, which allows for state-selective pumping and probing of molecules. By locking two near-infrared diode lasers to one cavity with a finesse at the order of 105, we measured all three types of double resonances. Carbon monoxide molecules with selected speeds along the laser beam were excited to vibrationally excited states, and absorption spectra with sub-MHz linewidths were observed. Positions of double resonance transitions were determined with an accuracy of 3.7 kHz, which was verified by comparing to Lamb-dip measurements. The present work paves the way to the pump-probe study of highly excited molecules with unprecedented precision.

Testing for SARS-CoV-2 among cruise ship travelers repatriated to the United States, February to March 2020

BackgroundIn early 2020, an outbreak of coronavirus disease 2019 occurred among passengers and crew of the Diamond Princess cruise ship. During February 16-17, some US citizens, residents, and their partners voluntarily repatriated to the US from Japan. MethodsWe conducted a retrospective, longitudinal evaluation of repatriated travelers where the outcome of interest was a positive test for SARS-CoV-2. Travelers who tested positive for SARS-CoV-2 were isolated in hospitals or at home under county isolation orders and underwent serial testing by real-time reverse transcription polymerase chain reaction (RT-PCR) approximately every other day, as contemporaneous US guidance required two consecutive negative tests collected [≥]24 hours apart and symptom improvement before release from isolation. ResultsAmong quarantined repatriated travelers, 14% tested positive for SARS-CoV-2. One-fifth of infected travelers initially tested negative but were identified on subsequent testing. All infected travelers remained asymptomatic or developed mild symptoms during isolation. Many travelers remained in prolonged isolation because of persistent viral detection based on contemporaneous policies. ConclusionOur findings support testing within 3-5 days after possible SARS-CoV-2 exposure to comprehensively identify infections and mitigate transmission and lend support to symptom- and time-based isolation recommendations, rather than test-based criteria.

Cavity ring-down spectroscopy based on a comb-locked optical parametric oscillator source.

Spectroscopy of molecules in the mid-infrared (MIR) region has important applications in various fields, such as astronomical observation, environmental detection, and fundamental physics. However, compared to that in the near-infrared, precision spectroscopy in the MIR is often limited by the light source and has not shown full potential in sensitivity. Here we report a cavity ring-down spectroscopy system using a tunable narrow-linewidth optical parametric oscillator, which fulfills the requirement of high sensitivity and high precision in the MIR region. The Lamb-dip spectrum of the N2O molecule at 2.7 µm was measured as a demonstration of spectroscopy in the MIR with kilohertz accuracy.

Systematic Screening and Deep Analysis of CoPt Binding Peptides Leads to Enhanced CoPt Nanoparticles Using Designed Peptides.

Using protein and peptide additives to direct the crystallization of inorganic materials is a very attractive and environmentally friendly strategy to access complex and sometimes inaccessible mineral phases. CoPt is a very desirable high-magnetoanisotropic material in its L10 phase, but this is acquired by annealing at high temperatures which is incompatible with delicate nanomaterial assembly. Previous studies identified one peptide with high affinity to CoPt and four peptides with high affinity to FePt L10 phase nanoparticles (NPs) through phage display biopanning selection. While synthesis mediated by these peptides offered a small degree of L10 character to the NPs, they do not have the magnetoanistropy required for applications. In this study, we improve the activity of peptide directed crystallization by designing second generation peptides. We use the five literature sequences (LS) to probe the binding affinity deeper through dissection (alanine scanning), reduction (truncations), and substitution of the LS to find key amino acids and motifs. This is performed using a SPOT peptide array, importantly probing interactions at three stages of NP formation: with precursor, during synthesis, and with NPs. We found four universal features: 1) the importance of basic residues, particularly lysine flanking both ends of the sequence; 2) the importance of methionine; 3) shorter sequences show higher affinity than longer ones; and 4) acidic residues have a negative impact on binding with aspartic acid less favorable than glutamic acid. However, an acidic amino acid benefits, presumably to balance charge. The short motif KSLS had high affinity in all assays. Three sequences were selected from the screening, and three sequences were designed from the rules above. These were used to mediate a green synthesis of CoPt nanoparticles. The screened peptides mediated the formation of NPs with improved coercivity (90-110 Oe) compared to the LS (30-80 Oe), while the designed peptides facilitated formation of CoPt NPs with the highest coercivity (109 to 132 Oe), representing a massive improvement on L10 character. This result along with deeper insight this methodology brings offers vast potential for the future.

Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.

Seeded optical parametric oscillator light source for precision spectroscopy.

Precision spectroscopy of fundamental bands of molecules in the mid-infrared (MIR) region is of great interest in applications of trace detection and testing fundamental physics, where high-power and narrow-linewidth MIR lasers are needed. By using a frequency-stabilized near-infrared laser as a seed of the signal light of a continuous-wave optical parametric oscillator, we established a broadly tunable MIR light source that has an output power of several hundred milliwatts and a linewidth of a few tens of kilohertz. The MIR laser frequency drift was reduced to below 1 kHz by using an optical frequency comb to stabilize the frequency of the 1064 nm pumping laser. The performance of the light source was investigated and tested by measuring the saturated absorption spectroscopy of a few molecular transitions at 3.3 µm.

Quality of reporting in systematic reviews published in dermatology journals.

BACKGROUND: Reporting of systematic reviews (SRs) using PRISMA increases transparency and reproducibility; adherence in the dermatology literature has not been assessed. OBJECTIVES: To assess selected, primarily methodological items from the PRISMA reporting guideline among SRs published in dermatology journals. METHODS: We reviewed SRs published from 2013 to 2017 in the five highest-impact dermatology journals according to the Science Citation Index. We descriptively assessed reporting of selected PRISMA items, the proportion of PRISMA items fully and partially reported, and whether SRs described using a preregistered protocol. We used univariate and multivariate linear regression to evaluate associations between exposures (year, protocol registration, funding source, type of included study, disease and journal), and outcomes (proportion of PRISMA items fully reported, and fully and partially reported, for each SR). RESULTS: We identified 136 SRs. All had more than one inadequately reported PRISMA item. Protocol registration (73%) and risk of bias (38%) were most often unreported. Reporting improved over time in our primary multivariate analysis [fully reported vs. partially and not reported, ß = 2·48; 95% confidence interval (CI) 0·73-4·27] and secondary analysis (fully and partially reported vs. not reported, ß = 1·28, 95% CI 0·06-2·50). Only 15% (20 of 136) of SRs stated that their protocols were registered; this was associated with PRISMA adherence to the evaluated PRISMA items in our primary multivariate analysis (ß = 10·05, 95% CI 2·89-17·2) and secondary analysis (ß = 8·87, 95% CI 3·84-13·9). CONCLUSIONS: SR reporting in dermatology journals is often inadequate but improving over time; protocol registration is associated with better reporting. What's already known about this topic? No studies to date have examined the adherence of dermatology systematic reviews (SRs) to reporting guidelines, such as PRISMA. In other medical fields, reporting is variable with some improvement in adherence to reporting standards over time. What does this study add? Among SRs published in five dermatology journals from 2013 to 2017, all (n = 136) had at least one inadequately reported PRISMA item, while 93% (127 of 136) had at least one fully nonreported item. Reporting improved over time and SRs that stated use of a preregistered protocol were associated with better reporting. Several items remain commonly underreported in dermatology SRs. Authors, reviewers, journal editors and editorial committees should encourage preregistration of SR protocols and improved SR reporting.

The effect of replacement of fish meal with Amino Acids and Optimized Protein Levels in the diet of the Nile Tilapia Oreochromis niloticus / O efeito da substituição da farinha de peixe por Aminoácidos e Níveis Otimizados de Proteína na dieta da tilápia do Nilo Oreochromis niloticus

Abstract This study was conducted to determine an appropriate replacement of fishmeal with amino acids (AAs) and optimized protein levels in practical diets for Oreochromis niloticus with mean initial body weight 12.52±0.63g. Six experimental and a control diet (total 7 diets) divided into two groups, and a control diet (D1) containing 32% protein. The first group contained three diets that included different dietary protein levels, viz. 20 (D2), 25 (D3), and 30% (D4) with AAs when replacing fishmeal by plant protein sources. In the second group, the diets were contained 20 (D5), 25 (D6), and 30% (D7) without AAs. The best growth performance was achieved in fish fed with diet D1. Total feed intake was increased with an increase in dietary protein level with AAs. The specific growth rate showed a similar pattern with a significant difference between control, D4 and D7 compared to other groups. The feed conversion ratio decreased when protein levels in the diets increased. The protein efficiency ratio showed a similar performance, with a slight increase between the control diet and diets with AAs. However, insignificant differences (P>0.05) were observed between diets with and without AAs. An economic evaluation indicated that inclusion of low fishmeal in tilapia diets reduced the price/kg of diets compared to control.

Resumo Este estudo foi realizado para determinar uma substituição adequada de farinha de peixe com aminoácidos (AA) e níveis otimizados de proteína em dietas práticas para Oreochromis niloticus com peso corporal inicial médio de 12,52 ± 0,63 g. Seis dietas experimentais e controle (total de 7 dietas) divididas em dois grupos, e uma dieta controle (D1) contendo 32% de proteína. O primeiro grupo continha três dietas que incluíam diferentes níveis de proteína na dieta, viz. 20 (D2), 25 (D3) e 30% (D4) com AAs ao substituir a farinha de peixe por fontes de proteína vegetal. No segundo grupo, as dietas continham 20 (D5), 25 (D6) e 30% (D7) sem AAs. O melhor desempenho de crescimento foi alcançado em peixes alimentados com dieta D1. O consumo total de ração foi aumentado com o aumento do nível de proteína na dieta com AAs. A taxa de crescimento específico mostrou um padrão semelhante com uma diferença significativa entre o controle, D4 ​​e D7 em comparação com outros grupos. A taxa de conversão alimentar diminuiu quando os níveis de proteína nas dietas aumentaram. A taxa de eficiência protéica apresentou desempenho semelhante, com discreto aumento entre a dieta controle e as dietas com AAs. Entretanto, diferenças insignificantes (P> 0,05) foram observadas entre dietas com e sem AAs. Uma avaliação econômica indicou que a inclusão de farinha de peixe baixa em dietas de tilápia reduziu o preço / kg de dietas em relação ao controle.

Factors associated with overall survival and relief of dysphagia in advanced esophageal cancer patients after 125I seed-loaded stent placement: a multicenter retrospective analysis.

Iodine-125 (125I) seed-loaded stent placement has served as an effective palliation for malignant esophageal strictures in China. We performed a retrospective study to identify the prognostic factors of this irradiation stent placement in advanced esophageal cancer patients. A total of 201 patients who underwent 125I seed-loaded stent placement were included in this study from June 2012 to March 2016 at five hospitals in China. The Cox regression models adjusted for stratification factors were used, and a stepwise multivariate analysis was performed to predict the overall survival and relief of dysphagia on the basis of pretreatment clinical characteristics, respectively. Three independent prognostic factors were identified for overall survival: histopathological subtype (squamous cell carcinoma vs. adenocarcinoma, hazard ratio [HR] 1.45, 95% confidence interval [CI95%]: 1.01-2.09, P = 0.046), serum total protein (≥66 g/L vs. <66 g/L, HR 0.61, CI95%: 0.48-0.59, P = 0.023), and performance status (<2 vs. ≥2, HR 1.57, CI95%: 1.09-2.08, P = 0.013). Four factors were significantly associated with the relief of dysphagia: T stage (T3 vs. T4, P = 0.003), tumor location (superior vs. inferior, P = 0.049), tumor-node-metastasis classification (IV vs. II, P = 0.025), and age (≥71 years vs. <71 years, P = 0.029). Prognostic factors identified from this analysis can be used to aid clinical decision-making and design future clinical trials.

From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination.

BACKGROUND: Substantial global progress in the control of malaria in recent years has led to increased commitment to its potential elimination. Whether this is possible in high transmission areas of sub-Saharan Africa remains unclear. Zanzibar represents a unique case study of such attempt, where modern tools and strategies for malaria treatment and vector control have been deployed since 2003. METHODS: We have studied temporal trends of comprehensive malariometric indices in two districts with over 100,000 inhabitants each. The analyses included triangulation of data from annual community-based cross-sectional surveys, health management information systems, vital registry and entomological sentinel surveys. RESULTS: The interventions, with sustained high-community uptake, were temporally associated with a major malaria decline, most pronounced between 2004 and 2007 and followed by a sustained state of low transmission. In 2015, the Plasmodium falciparum community prevalence of 0.43% (95% CI 0.23-0.73) by microscopy or rapid diagnostic test represented 96% reduction compared with that in 2003. The P. falciparum and P. malariae prevalence by PCR was 1.8% (95% CI 1.3-2.3), and the annual P. falciparum incidence was estimated to 8 infections including 2.8 clinical episodes per 1000 inhabitants. The total parasite load decreased over 1000-fold (99.9%) between 2003 and 2015. The incidence of symptomatic malaria at health facilities decreased by 94% with a trend towards relatively higher incidence in age groups > 5 years, a more pronounced seasonality and with reported travel history to/from Tanzania mainland as a higher risk factor. All-cause mortality among children < 5 years decreased by 72% between 2002 and 2007 mainly following the introduction of artemisinin-based combination therapies whereas the main reduction in malaria incidence followed upon the vector control interventions from 2006. Human biting rates decreased by 98% with a major shift towards outdoor biting by Anopheles arabiensis. CONCLUSIONS: Zanzibar provides new evidence of the feasibility of reaching uniquely significant and sustainable malaria reduction (pre-elimination) in a previously high endemic region in sub-Saharan Africa. The data highlight constraints of optimistic prognostic modelling studies. New challenges, mainly with outdoor transmission, a large asymptomatic parasite reservoir and imported infections, require novel tools and reoriented strategies to prevent a rebound effect and achieve elimination.