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Background: Intradiscal gas is frequently observed in older patients with disc degeneration and can occasionally result in nerve root compression. Case Description: A 79-year-old male patient presented with increasing left lower extremity sciatica. Lumbar computed tomography (CT) and magnetic resonance (MR) images revealed a left paramedian L5-S1 gas-containing disc herniation. Utilizing an interlaminar approach, a full-endoscopic discectomy (FED) was performed at L5-S1. During disc removal, we countered intradiscal gas bubbles. Postoperatively, the patient's symptoms/signs fully resolved, and follow-up MR and CT images revealed total resection of the disc herniation, and no further gas. Conclusion: Through an interlaminar FED, we effectively removed an L5-S1 MR/CT-documented gas-containing disc herniation.
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PURPOSE: We investigated the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) and attenuation imaging (ATI) in detecting fibrosis and steatosis in patients with chronic liver disease (CLD), comparing them with established methods. METHODS: In 190 patients with CLD, 2D-SWE and vibration-controlled transient elastography (VCTE) were used for liver stiffness measurement (LSM), and ATI and controlled attenuation parameter (CAP) were used for steatosis quantification. The correlations between these new and established methods were analyzed. RESULTS: Significant correlations were found between 2D-SWE and VCTE (r = 0.78, P < 0.001), and between ATI and CAP (r = 0.70, P < 0.001). Liver stiffness tended to be lower with 2D-SWE compared with that with VCTE, especially in cases with higher LSM, and ATI was less influenced by skin-capsular distance than CAP. Area under the receiver-operating characteristics curves (AUCs) and optimal cut-offs of 2D-SWE for diagnosing liver fibrosis stages F2, F3, and F4 were 0.73 (8.7 kPa), 0.79 (9.1 kPa), and 0.88 (11.6 kPa), respectively. The AUCs and optimal cut-offs of ATI for diagnosing hepatic steatosis grades S1, S2, and S3 were 0.91 (0.66 dB/cm/MHz), 0.80 (0.79 dB/cm/MHz), and 0.88 (0.86 dB/cm/MHz), respectively. A subgroup analysis of 86 patients with metabolic dysfunction-associated steatotic liver disease also demonstrated good performance for 2D-SWE and ATI. CONCLUSION: 2D-SWE and ATI performed comparably with conventional VCTE and CAP in evaluating CLD, offering reliable alternatives for diagnosing liver fibrosis and steatosis.
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Background: Nervous system involvement in immunoglobulin G4-related disease (IgG4-RD) has been rarely reported. Case Description: We describe an unusual case of IgG4-RD manifested as paresthesia in the right lower extremity. A 51-year-old male presented with paresthesia in the right S1-S3 regions. A neurological examination revealed peripheral neuropathy. Blood examination results were normal, barring slightly elevated IgG levels. Initial magnetic resonance imaging of the swollen right S1 and S2 nerve roots revealed lymphoma, schwannoma, and sarcoidosis. However, following the biopsy, the pathological findings were not typical of these diseases. Abdominal computed tomography revealed perirenal lesions, and IgG4-RD was suspected. The patient had a serum IgG4 level of 724 mg/dL. Additional pathological evaluations of the swollen S1 nerve revealed findings that corresponded to the diagnostic criteria for IgG4-RD. Oral steroid therapy was initiated, which improved paresthesia, and the swollen S1 nerve root gradually shrank. Conclusion: This report highlights a rare case of IgG4-RD involving nerve roots that neurosurgeons should consider.
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The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.
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Protein phosphorylation is a prevalent translational modification, and its dysregulation has been implicated in various diseases, including cancer. Despite its significance, there is a lack of specific inhibitors of the FCP/SCP-type Ser/Thr protein phosphatase Scp1, characterized by high specificity and affinity. In this study, we focused on adnectin, an antibody-mimetic protein, aiming to identify Scp1-specific binding molecules with a broad binding surface that target the substrate-recognition site of Scp1. Biopanning of Scp1 was performed using an adnectin-presenting phage library with a randomized FG loop. We succeeded in identifying FG-1Adn, which showed high affinity and specificity for Scp1. Ala scanning analysis of the Scp1-binding sequence in relation to the FG-1 peptide revealed that hydrophobic residues, including aromatic amino acids, play important roles in Scp1 recognition. Furthermore, FG-1Adn was found to co-localize with Scp1 in cells, especially on the plasma membrane. In addition, Western blotting analysis showed that FG-1Adn increased the phosphorylation level of the target protein of Scp1 in cells, indicating that FG-1Adn can inhibit the function of Scp1. These results suggest that FG-1Adn can be used as a specific inhibitor of Scp1.
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Anticorpos , Domínio de Fibronectina Tipo III , Proteínas Recombinantes , Aminoácidos Aromáticos , Fosfoproteínas Fosfatases , Biblioteca de PeptídeosRESUMO
Background: Primary extranodal marginal zone mucosa-associated lymphoid tissue-type B-cell lymphoma (EMZMBCL), which presents as a dural mass, is a rare intracranial tumor that mimics a subdural hematoma or meningioma. Case Description: A 49-year-old woman presented to our hospital with transient right upper limb paresis, dysarthria for 10 min, and ongoing right upper-limb numbness. Computed tomography (CT) of the head revealed extra-axial lesions in the left frontal and parietal lobes. Based on the initial CT findings in the emergency room, an acute subdural hematoma was suspected. However, meningiomas and other intracranial tumors were also listed as differential diagnoses because there was no history of head trauma or coagulation abnormalities on blood examination, and further imaging studies were performed. Imaging findings suggested a subdural neoplastic lesion. A partial resection was performed for the lesion. Based on histopathological and immunohistochemical examinations, the patient was diagnosed with EMZMBCL. Whole-brain and intensity-modulated radiation therapies were administered as adjuvant therapies. The patient was discharged without neurological deficits. Conclusion: EMZMBCL is a rare disease that should be considered in the differential diagnosis of subdural lesions, especially when there is no history of trauma or abnormalities in the coagulation system. The patient had a favorable outcome after selecting radiotherapy as the adjuvant therapy.
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Accurately quantifying the burden of malaria over time is an important goal of malaria surveillance efforts and can enable effective targeting and evaluation of interventions. Malaria surveillance methods capture active or recent infections which poses several challenges to achieving malaria surveillance goals. In high transmission settings, asymptomatic infections are common and therefore accurate measurement of malaria burden demands active surveillance; in low transmission regions where infections are rare accurate surveillance requires sampling large subsets of the population; and in any context monitoring malaria burden over time necessitates serial sampling. Antibody responses to Plasmodium falciparum parasites persist after infection and therefore measuring antibodies has the potential to overcome several of the current obstacles to accurate malaria surveillance. Identifying which antibody responses are markers of the timing and intensity of past exposure to P. falciparum remains challenging, particularly among adults who tend to be re-exposed multiple times over the course of their lifetime and therefore have similarly high antibody responses to many Plasmodium antigens. A previous analysis of 479 serum samples from individuals in three regions in southern Africa with different historical levels of P. falciparum malaria transmission (high, intermediate, and low) revealed regional differences in antibody responses to P. falciparum antigens among children under 5 years of age. Using a novel bioinformatic pipeline optimized for protein microarrays that minimizes between-sample technical variation, we used antibody responses to Plasmodium antigens as predictors in random forest models to classify samples from adults into these three regions of differing historical malaria transmission with high accuracy (AUC = 0.99). Many of the most important antigens for classification in these models do not overlap with previously published results and are therefore novel candidate markers for the timing and intensity of past exposure to P. falciparum. Measuring antibody responses to these antigens could lead to improved malaria surveillance.
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Metal ions are used in various situations in living organisms and as a part of functional materials. Since the excessive intake of metal ions can cause health hazards and environmental pollution, the development of new molecules that can monitor metal ion concentrations with high sensitivity and selectivity is strongly desired. DNA can form various structures, and these structures and their properties have been used in a wide range of fields, including materials, sensors, and drugs. Guanine-rich sequences respond to metal ions and form G-quadruplex structures and G-wires, which are the self-assembling macromolecules of G-quadruplex structures. Therefore, guanine-rich DNA can be applied to a metal ion-detection sensor and functional materials. In this study, the IRDAptamer library originally designed based on G-quadruplex structures was used to screen for Mn2+, which is known to induce neurodegenerative diseases. Circular dichroism and fluorescence analysis using Thioflavin T showed that the identified IRDAptamer sequence designated MnG4C1 forms a non-canonical G-quadruplex structure in response to low concentrations of Mn2+. A serum resistance and thermostability analysis revealed that MnG4C1 acquired stability in a Mn2+-dependent manner. A Förster resonance energy transfer (FRET) system using fluorescent molecules attached to the termini of MnG4C1 showed that FRET was effectively induced based on Mn2+-dependent conformational changes, and the limit of detection (LOD) was 0.76 µM for Mn2+. These results suggested that MnG4C1 can be used as a novel DNA-based Mn2+-detecting molecule.
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Técnicas Biossensoriais , Quadruplex G , DNA/química , Técnicas Biossensoriais/métodos , Íons , Guanina/químicaRESUMO
BACKGROUND: Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, including assessing residual transmission across seasons and importation of malaria into these regions. METHODS: In a low and seasonal transmission setting of southern Zambia, a total of 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 and 2018 were genotyped using molecular inversion probes (MIPs n = 1793) targeting a total of 1832 neutral and geographically informative SNPs distributed across the parasite genome. After filtering for quality and missingness, 302 samples and 1410 SNPs were retained and used for downstream population genomic analyses. RESULTS: The analyses revealed most (67%, n = 202) infections harboured one clone (monogenomic) with some variation at local level suggesting low, but heterogenous malaria transmission. Relatedness identity-by-descent (IBD) analysis revealed variable distribution of IBD segments across the genome and 6% of pairs were highly-related (IBD ≥ 0.25). Some of the highly-related parasite populations persisted across multiple seasons, suggesting that persistence of malaria in this low-transmission region is fueled by parasites "seeding" across the dry season. For recent years, clusters of clonal parasites were identified that were dissimilar to the general parasite population, suggesting parasite populations were increasingly fragmented at small spatial scales due to intensified control efforts. Clustering analysis using PCA and t-SNE showed a lack of substantial parasite population structure. CONCLUSION: Leveraging both genomic and epidemiological data provided comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia over 7 years.
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Malária Falciparum , Malária , Parasitos , Animais , Humanos , Plasmodium falciparum/genética , Malária Falciparum/parasitologia , Zâmbia/epidemiologia , Análise Espacial , GenômicaRESUMO
Obtaining accurate malaria surveillance data is challenging in low-transmission settings because large sample sizes are required to estimate incidence and prevalence precisely. Serology is an additional tool to document progress toward malaria elimination. An enzyme immunoassay to Plasmodium falciparum lysate was used to estimate age-specific seroprevalence among residents of southern Zambia, where malaria transmission has declined to pre-elimination levels during the past two decades. Plasma was eluted from 3,362 dried blood spots collected during five cross-sectional surveys conducted between 2009 and 2012, and again in 2018. Annual seroconversion rates (SCRs), an estimate of the force of infection, were calculated using a reversible catalytic model. The SCR decreased by two thirds from a level of approximately 0.15/year in 2009 and 2010 to approximately 0.05/year in 2011 and 2012, and then decreased 5-fold to 0.01/year by 2018, demonstrating the utility of serology in documenting progress toward elimination.
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Malária Falciparum , Malária , Humanos , Plasmodium falciparum , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Zâmbia/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais , Soroconversão , Malária/epidemiologia , Fatores EtáriosRESUMO
Background: Spontaneous anterior arch fracture of the atlas after a C1 laminectomy (CIL) is an extremely rare complication. Case Description: A 72-year-old male presented with the sudden onset of neck pain. His prior history included; a CIL for atlantoaxial subluxation, shunt closure for a spinal dural arteriovenous fistula at C3, a cervical laminoplasty from C3 to C6 for stenosis, and a prior anterior C4/5 and C5/6 fusion 14 years ago. Once the computed tomography documented a right C1 anterior arch fracture, and occipital-cervical fusion was performed utilizing C2 laminar screws and C4 pedicle screws with halo-vest placement. Postoperatively, the neck pain resolved and he remained stable. Conclusion: Neurosurgeons should be aware of the risk of anterior arch fractures following a CIL and may alternatively consider a C1 laminoplasty in the future.
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Protein microarrays are a promising technology that measure protein levels in serum or plasma samples. Due to their high technical variability and high variation in protein levels across serum samples in any population, directly answering biological questions of interest using protein microarray measurements is challenging. Analyzing preprocessed data and within-sample ranks of protein levels can mitigate the impact of between-sample variation. As for any analysis, ranks are sensitive to preprocessing, but loss function based ranks that accommodate major structural relations and components of uncertainty are very effective. Bayesian modeling with full posterior distributions for quantities of interest produce the most effective ranks. Such Bayesian models have been developed for other assays, for example, DNA microarrays, but modeling assumptions for these assays are not appropriate for protein microarrays. Consequently, we develop and evaluate a Bayesian model to extract the full posterior distribution of normalized protein levels and associated ranks for protein microarrays, and show that it fits well to data from two studies that use protein microarrays produced by different manufacturing processes. We validate the model via simulation and demonstrate the downstream impact of using estimates from this model to obtain optimal ranks.
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Análise Serial de Proteínas , Humanos , Teorema de Bayes , Simulação por Computador , Análise de Sequência com Séries de OligonucleotídeosRESUMO
BACKGROUND: The clinical outcomes and radiographic changes of a one-stage procedure combining cervical laminoplasty and unilateral cervical foraminotomy for patients with coexisting cervical myelopathy and unilateral radiculopathy were evaluated. METHODS: Seven patients (two females and five males) with coexisting cervical myelopathy and unilateral cervical radiculopathy were included in this study. The mean age was 58.4 years (range 45-77 years). Cervical laminoplasty and unilateral cervical foraminotomy were performed on the recruited patients in a single stage. The quantitative clinical changes between the preoperative and 6-month postoperative assessment were analyzed using the Japanese Orthopedic Association (JOA) score, the JOA Cervical Myelopathy Evaluation Questionnaire (JOA-CMEQ), visual analog scale (VAS), and Neck Disability Index (NDI). Moreover, the preoperative and 6-month postoperative radiographic changes were assessed using the C2-7 angle and range of motion (ROM) between flexion and extension angle. RESULTS: There were significant differences in QOL in the JOA-CMEQ between the groups. Furthermore, the postoperative VAS values in the arms and hands generally improved, although not significantly, between the groups. CONCLUSIONS: The aforementioned surgical procedure may be safe and efficient for patients with coexisting cervical myelopathy and radiculopathy.
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Foraminotomia , Laminoplastia , Radiculopatia , Doenças da Medula Espinal , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Radiculopatia/cirurgia , Laminoplastia/métodos , Qualidade de Vida , Resultado do Tratamento , Vértebras Cervicais/cirurgia , Doenças da Medula Espinal/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Spinal cysts in the interdural space are extremely rare and are not included in the standard classification of spinal meningeal cysts. OBSERVATIONS: A 60-year-old female presented to our hospital with a spastic gait and numbness in both palms. Magnetic resonance imaging (MRI) revealed a spinal cyst from C4 to T4 compressing the spinal cord. Computed tomography myelography revealed a fistula at C4-5 and C5-6 that connected the cyst along the right C5 and C6 root sleeves. The cyst was located within the dura mater, and communication with the arachnoid space was achieved using a shunt tube. There was partial spastic gait amelioration after the procedure, but the patient experienced a relapse 2 months postoperation. A repeat procedure was performed without a shunt tube to allow greater communication between the cyst and the subarachnoid space. After this, marked improvement in gait function was observed, and MRI showed a significant reduction in cyst volume. LESSONS: Interdural spinal meningeal cysts are rare. When the interdural cyst cannot be removed entirely, surgery may be appropriate for providing a shunt tube or establishing communication between the cyst and arachnoid space to maintain the circulation of cerebrospinal fluid collected in the cyst cavity.
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BACKGROUND: Spinal subdural epiarachnoid hygroma (SSEH) after lumbar laminectomy is an extremely rare complication. OBSERVATIONS: An 84-year-old man presented to the hospital with lower back pain, radicular pain, and numbness in the lateral aspect of the left leg. Magnetic resonance imaging (MRI) revealed anterior lumbar spondylolisthesis at L3, severe disc herniation at L3-4, and severe lumbar spinal canal stenosis at L3-4 and L4-5. Lumbar laminectomy at L3-4 and L4-5 and discectomy at L3-4 were performed without complications such as cerebrospinal fluid (CSF) leakage and durotomy intraoperatively. Although lower back pain and numbness at the lateral aspect of the left leg were resolved postoperatively, postoperative MRI showed spinal nerve deviation to the ventral side due to SSEH from T12 to S1. Conservative therapy was performed for asymptomatic SSEH, and MRI 1 week postoperatively indicated improved ventral spinal nerve deviation and reduced SSEH. LESSONS: SSEHs after posterior decompression without durotomy are extremely rare. Asymptomatic SSEHs may resolve with conservative treatment. However, surgery should be performed to decompress hygroma in patients with symptomatic SSEH.
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BACKGROUND: Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare. OBSERVATIONS: A 50-year-old man presented to our hospital with numbness of the left posterior rib region, back, and bilateral lower limbs. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed an intramedullary lesion at T2-T3 with no contrast enhancement. The patient opted for conservative treatment. Eighteen months after the first consultation, the patient presented with slowly progressive numbness of the bilateral upper limbs, paraparesis, and dysuria, with rapid deterioration over the following 3 months. T1- and T2-weighted MRI revealed expansion of the intramedullary lesion, which extended from C7 to T5, and syringomyelia at C5-C6. Contrast-enhanced T1-weighted MRI revealed an enhancing intramedullary lesion at C7-T5. Open biopsy and C5-T5 laminectomy were performed for diagnosis and decompression. PA with anaplasia was diagnosed based on pathological and immunohistochemical findings. The patient received postoperative radiotherapy and chemotherapy. LESSONS: Rapidly progressive IMSC PA with a change in contrast enhancement is extremely rare in adults. PA may undergo a spontaneous malignant transformation during its natural clinical course. In this case, the change in contrast enhancement may have been associated with the malignant transformation of the PA.
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Human movement drives spatial transmission patterns of infectious diseases. Population-level mobility patterns are often quantified using aggregated data sets, such as census migration surveys or mobile phone data. These data are often unable to quantify individual-level travel patterns and lack the information needed to discern how mobility varies by demographic groups. Individual-level datasets can capture additional, more precise, aspects of mobility that may impact disease risk or transmission patterns and determine how mobility differs across cohorts; however, these data are rare, particularly in locations such as sub-Saharan Africa. Using detailed GPS logger data collected from three sites in southern Africa, we explore metrics of mobility such as percent time spent outside home, number of locations visited, distance of locations, and time spent at locations to determine whether they vary by demographic, geographic, or temporal factors. We further create a composite mobility score to identify how well aggregated summary measures would capture the full extent of mobility patterns. Although sites had significant differences in all mobility metrics, no site had the highest mobility for every metric, a distinction that was not captured by the composite mobility score. Further, the effects of sex, age, and season on mobility were all dependent on site. No factor significantly influenced the number of trips to locations, a common way to aggregate datasets. When collecting and analyzing human mobility data, it is difficult to account for all the nuances; however, these analyses can help determine which metrics are most helpful and what underlying differences may be present.
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Telefone Celular , Doenças Transmissíveis , Humanos , Viagem , Inquéritos e QuestionáriosRESUMO
For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.
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Inseticidas , Malária , Parasitos , África Central , Animais , Criança , Estudos Transversais , Humanos , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos , Zâmbia/epidemiologia , Zimbábue/epidemiologiaRESUMO
The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.