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1.
J Med Econ ; 26(1): 1469-1478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37916295

RESUMO

AIMS: This study aimed to evaluate the value and affordability of insulin glargine 300 U/mL (Gla-300) in a budget impact model from a United States (U.S.) payer perspective by leveraging recent real-world evidence (RWE) studies and incorporating the recent insulin price caps where applicable. MATERIALS AND METHODS: An economic model for a hypothetical one million U.S. health-plan population was developed to assess the budgetary impact of therapeutic interchanges in either direction between the two long- and longer-acting basal insulins (BIs) for patients with type 2 diabetes over a three-year model horizon. The utilization of long-acting BIs, longer-acting BIs, biosimilar BIs, and insulin degludec (IDeg-100) were informed by IQVIA data and internal forecasting at Sanofi. The DELIVER-2 and DELIVER-naïve studies provided healthcare resource utilization (HCRU) parameters. In the model base case, 24% of patients switched from long-acting BIs to insulin glargine biosimilars, IDeg-100, and other longer-acting BIs (Gla-300) by projected year 3. RESULTS: The base case total costs were $10,145 per patient per year (PPPY) in year 3 for the cumulative population. When all patients switched to Gla-300, the total costs in year 3 were $8,799, reflecting a net savings of -$660 PPPY compared to the budget increase of $686 PPPY in the base case. However, the longer-acting to long-acting BIs reversal scenario demonstrated a budgetary decrease of $676 PPPY over the model horizon. The reduction in incremental PPPY cost of $93 was observed using net drug costs rather than wholesale acquisition costs (WAC). LIMITATIONS: The market shares for years 1-3 were based on expectations supported by the clinicians' expert opinions and were not obtained from real-world data. CONCLUSIONS: The economic value of increased utilization of Gla-300 was driven by the reduction in HCRU, costs and market shares assumptions. Budgetary reductions were achieved by switching patients from long-acting BIs to Gla-300.


Type 2 Diabetes (T2D) is a chronic and debilitating condition that can lead to severe macro or microvascular complications. To mitigate these complications, it is crucial to effectively manage blood glucose levels. When other treatments prove ineffective in achieving adequate glucose control, insulin-based therapy becomes necessary. However, insulin-based treatments often come with the risk of hypoglycemic episodes, which can lead to increased utilization of healthcare resources (HCRU) and have a negative impact on costs.This study aimed to assess the budgetary impact of higher market shares of longer-acting basal insulins (specifically insulin glargine Gla-300) compared to long-acting basal insulins, insulin glargine biosimilars, and insulin degludec (IDeg) in the treatment of T2D. The perspective taken was that of a U.S. payer, taking into account the recent insulin price caps where applicable.The economic benefit of increased utilization of Gla-300 was driven by reductions in HCRU, costs, and market share assumptions. This resulted in a budgetary increase of $686 per patient per year (PPPY). In an alternative scenario where all patients transitioned to Gla-300, it led to a net savings of $660 PPPY.These findings provide valuable insights for decision-makers and healthcare professionals when making choices related to formulary placement and treatment utilization.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2 , Humanos , Estados Unidos , Insulina Glargina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Insulina , Modelos Econômicos , Hipoglicemiantes/uso terapêutico
2.
Diabetes Ther ; 14(12): 2109-2125, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801225

RESUMO

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

3.
Diabetes Ther ; 14(8): 1331-1344, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37289358

RESUMO

INTRODUCTION: The fixed-ratio combination of insulin glargine (iGlar) plus lixisenatide (iGlarLixi) has proven efficacious in clinical trials; however, there is limited evidence of its benefits in a variety of real-world patients with type 2 diabetes mellitus (T2DM) who present in routine clinical practice. METHODS: A large integrated claims and EHR database was used to identify two real-world (RW) cohorts (ages ≥ 18) with T2DM who were eligible for treatment with iGlarLixi. At baseline, the first cohort (insulin cohort) received insulin with or without oral antidiabetic drugs (OADs), and the second cohort (OAD-only cohort) received OADs only. A Monte Carlo patient-level simulation was applied to each cohort based on treatment strategies and efficacies from the LixiLan-L and LixiLan-O trials to estimate reductions in glycated hemoglobin A1C (A1C) and the percentage achieving age-based A1C goals (≤ 7% for ages < 65 and ≤ 8% for ages ≥ 65) at 30 weeks. RESULTS: The RW insulin (N = 3797) and OAD-only (N = 17,633) cohorts differed considerably in demographics, age, clinical characteristics, baseline A1C levels, and background OAD therapies compared to the populations in the Lixilan-L and Lixilan-O trials. Regardless of the cohort description, A1C goals were achieved among 52.6% vs. 31.6% (p < 0.001) of patients in the iGlarLixi vs. the iGlar arms in the insulin cohort simulation, while A1C goals were achieved among 59.9% vs. 49.3% and 32.8% (p < 0.001) of patients in the OAD-only cohort simulation in the iGlarLixi vs. the iGlar and lixisenatide arms, respectively. CONCLUSIONS: Irrespective of the treatment regimen at baseline (insulin vs. OAD only), this patient-level simulation demonstrated that a greater proportion of patients achieved their A1C goals with iGlarlixi compared to iGlar or lixisenatide alone. These findings suggest that the benefits of iGlarLixi extend to clinically distinct RW populations.

4.
J Comp Eff Res ; 12(8): e230065, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37387403

RESUMO

Aim: To evaluate the clinical and economic impact of antiarrhythmic drugs (AADs) compared with ablation both as individual treatments and as combination therapy without/with considering the order of treatment among patients with atrial fibrillation (AFib). Materials & methods: A budget impact model over a one-year time horizon was developed to assess the economic impact of AADs (amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, and as a group) versus ablation across three scenarios: direct comparisons of individual treatments, non-temporal combinations, and temporal combinations. The economic analysis was conducted in accordance with CHEERS guidance as per current model objectives. Results are reported as costs per patient per year (PPPY). The impact of individual parameters was evaluated using one-way sensitivity analysis (OWSA). Results: In direct comparisons, ablation had the highest annual medication/procedure cost ($29,432), followed by dofetilide ($7661), dronedarone ($6451), sotalol ($4552), propafenone ($3044), flecainide ($2563), and amiodarone ($2538). Flecainide had the highest costs for long-term clinical outcomes ($22,964), followed by dofetilide ($17,462), sotalol ($15,030), amiodarone ($12,450), dronedarone ($10,424), propafenone ($7678) and ablation ($9948). In the non-temporal scenario, total costs incurred for AADs (group) + ablation ($17,278) were lower compared with ablation alone ($39,380). In the temporal scenario, AADs (group) before ablation resulted in PPPY cost savings of ($22,858) compared with AADs (group) after ablation ($19,958). Key factors in OWSA were ablation costs, the proportion of patients having reablation, and withdrawal due to adverse events. Conclusion: Utilization of AADs as individual treatment or in combination with ablation demonstrated comparable clinical benefits along with costs savings in patients with AFib.


Assuntos
Amiodarona , Fibrilação Atrial , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Antiarrítmicos/uso terapêutico , Dronedarona/efeitos adversos , Sotalol/uso terapêutico , Propafenona/uso terapêutico , Flecainida/uso terapêutico , Amiodarona/efeitos adversos
5.
J Comp Eff Res ; 12(4): e220196, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36916711

RESUMO

Aim: The budgetary consequences of increasing dronedarone utilization for treatment of atrial fibrillation were evaluated from a US payer perspective. Materials & methods: A budget impact model over a 5-year time horizon was developed, including drug-related costs and risks for long-term clinical outcomes (LTCOs). Treatments included antiarrhythmic drugs (AADs; dronedarone, amiodarone, sotalol, propafenone, dofetilide, flecainide), rate control medications, and ablation. Direct comparisons and temporal and non-temporal combination scenarios investigating treatment order were analyzed as costs per patient per month (PPPM). Results: By projected year 5, costs PPPM for dronedarone versus other AADs decreased by $37.69 due to fewer LTCOs, treatment with dronedarone versus ablation or rate control medications + ablation resulted in cost savings ($359.94 and $370.54, respectively), and AADs placed before ablation decreased PPPM costs by $242 compared with ablation before AADs. Conclusion Increased dronedarone utilization demonstrated incremental cost reductions over time.


Assuntos
Amiodarona , Fibrilação Atrial , Humanos , Dronedarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Amiodarona/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Sotalol/uso terapêutico
6.
Proc Natl Acad Sci U S A ; 104(39): 15508-13, 2007 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-17873062

RESUMO

Genes encoding type VI secretion systems (T6SS) are widely distributed in pathogenic Gram-negative bacterial species. In Vibrio cholerae, T6SS have been found to secrete three related proteins extracellularly, VgrG-1, VgrG-2, and VgrG-3. VgrG-1 can covalently cross-link actin in vitro, and this activity was used to demonstrate that V. cholerae can translocate VgrG-1 into macrophages by a T6SS-dependent mechanism. Protein structure search algorithms predict that VgrG-related proteins likely assemble into a trimeric complex that is analogous to that formed by the two trimeric proteins gp27 and gp5 that make up the baseplate "tail spike" of Escherichia coli bacteriophage T4. VgrG-1 was shown to interact with itself, VgrG-2, and VgrG-3, suggesting that such a complex does form. Because the phage tail spike protein complex acts as a membrane-penetrating structure as well as a conduit for the passage of DNA into phage-infected cells, we propose that the VgrG components of the T6SS apparatus may assemble a "cell-puncturing device" analogous to phage tail spikes to deliver effector protein domains through membranes of target host cells.


Assuntos
Actinas/metabolismo , Actinas/química , Trifosfato de Adenosina/química , Animais , Bacteriófagos/metabolismo , Transporte Biológico , Reagentes de Ligações Cruzadas/química , DNA/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Dictyostelium/metabolismo , Escherichia coli/metabolismo , Plasmídeos/metabolismo , Conformação Proteica , Estrutura Terciária de Proteína
7.
Appl Environ Microbiol ; 73(5): 1501-13, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17220265

RESUMO

The development of new genetic systems for studying the complex regulatory events that occur within Borrelia burgdorferi is an important goal of contemporary Lyme disease research. Although recent advancements have been made in the genetic manipulation of B. burgdorferi, there still remains a paucity of basic molecular systems for assessing differential gene expression in this pathogen. Herein, we describe the adaptation of two powerful genetic tools for use in B. burgdorferi. The first is a Photinus pyralis firefly luciferase gene reporter that was codon optimized to enhance translation in B. burgdorferi. Using this modified reporter, we demonstrated an increase in luciferase expression when B. burgdorferi transformed with a shuttle vector encoding the outer surface protein C (OspC) promoter fused to the luciferase reporter was cultivated in the presence of fresh rabbit blood. The second is a lac operator/repressor system that was optimized to achieve the tightest degree of regulation. Using the aforementioned luciferase reporter, we assessed the kinetics and maximal level of isopropyl-beta-D-thiogalactopyranoside (IPTG)-dependent gene expression. This lac-inducible expression system also was used to express the gene carried on lp25 required for borrelial persistence in ticks (bptA). These advancements should be generally applicable for assessing further the regulation of other genes potentially involved in virulence expression by B. burgdorferi.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/metabolismo , Genes Reporter , Luciferases/metabolismo , Proteínas Repressoras/metabolismo , Animais , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Borrelia burgdorferi/crescimento & desenvolvimento , Vaga-Lumes/enzimologia , Regulação Bacteriana da Expressão Gênica , Técnicas Genéticas , Isopropiltiogalactosídeo , Repressores Lac , Luciferases/genética , Dados de Sequência Molecular , Proteínas Repressoras/genética , Análise de Sequência de DNA
8.
J Bacteriol ; 187(14): 4822-9, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15995197

RESUMO

Outer surface lipoprotein C (OspC) is a key virulence factor of Borrelia burgdorferi. ospC is differentially regulated during borrelial transmission from ticks to rodents, and such regulation is essential for maintaining the spirochete in its natural enzootic cycle. Recently, we showed that the expression of ospC in B. burgdorferi is governed by a novel alternative sigma factor regulatory network, the RpoN-RpoS pathway. However, the precise mechanism by which the RpoN-RpoS pathway controls ospC expression has been unclear. In particular, there has been uncertainty regarding whether ospC is controlled directly by RpoS (sigma(s)) or indirectly through a transactivator (induced by RpoS). Using deletion analyses and genetic complementation in an OspC-deficient mutant of B. burgdorferi, we analyzed the cis element(s) required for the expression of ospC in its native borrelial background. Two highly conserved upstream inverted repeat elements, previously implicated in ospC regulation, were not required for ospC expression in B. burgdorferi. Using similar approaches, a minimal promoter that contained a canonical -35/-10 sequence necessary and sufficient for sigma(s)-dependent regulation of ospC was identified. Further, targeted mutagenesis of a C at position -15 within the extended -10 region of ospC, which is postulated to function like the strategic C residue important for Esigma(s) binding in Escherichia coli, abolished ospC expression. The minimal ospC promoter also was responsive to coumermycin A(1), further supporting its sigma(s) character. The combined data constitute a body of evidence that the RpoN-RpoS regulatory network controls ospC expression by direct binding of sigma(s) to a sigma(s)-dependent promoter of ospC. The implication of our findings to understanding how B. burgdorferi differentially regulates ospC and other ospC-like genes via the RpoN-RpoS regulatory pathway is discussed.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/genética , Proteínas de Ligação a DNA/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Regulação Bacteriana da Expressão Gênica , Fator sigma/metabolismo , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Sequência de Bases , Primers do DNA , Proteínas de Escherichia coli , Teste de Complementação Genética , Dados de Sequência Molecular , Mutagênese , Plasmídeos , Regiões Promotoras Genéticas , RNA Polimerase Sigma 54 , Mapeamento por Restrição , Deleção de Sequência
9.
Proc Natl Acad Sci U S A ; 102(19): 6972-7, 2005 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-15860579

RESUMO

Borrelia burgdorferi (Bb), the agent of Lyme disease, is a zoonotic spirochetal bacterium that depends on arthropod (Ixodes ticks) and mammalian (rodent) hosts for its persistence in nature. The quest to identify borrelial genes responsible for Bb's parasitic dependence on these two diverse hosts has been hampered by limitations in the ability to genetically manipulate virulent strains of Bb. Despite this constraint, we report herein the inactivation and genetic complementation of a linear plasmid-25-encoded gene (bbe16) to assess its role in the virulence, pathogenesis, and survival of Bb during its natural life cycle. bbe16 was found to potentiate the virulence of Bb in the murine model of Lyme borreliosis and was essential for the persistence of Bb in Ixodes scapularis ticks. As such, we have renamed bbe16 a gene encoding borrelial persistence in ticks (bpt)A. Although protease accessibility experiments suggested that BptA as a putative lipoprotein is surface-exposed on the outer membrane of Bb, the molecular mechanism(s) by which BptA promotes Bb persistence within its tick vector remains to be elucidated. BptA also was shown to be highly conserved (>88% similarity and >74% identity at the deduced amino acid levels) in all Bb sensu lato strains tested, suggesting that BptA may be widely used by Lyme borreliosis spirochetes for persistence in nature. Given Bb's absolute dependence on and intimate association with its arthropod and mammalian hosts, BptA should be considered a virulence factor critical for Bb's overall parasitic strategy.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/fisiologia , Borrelia burgdorferi/metabolismo , Borrelia burgdorferi/patogenicidade , Doença de Lyme/microbiologia , Carrapatos/microbiologia , Animais , Clonagem Molecular , Endopeptidase K/farmacologia , Teste de Complementação Genética , Vetores Genéticos , Camundongos , Camundongos Endogâmicos C3H , Microscopia de Fluorescência , Modelos Genéticos , Dados de Sequência Molecular , Peptídeo Hidrolases/metabolismo , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase , Fatores de Tempo , Virulência
10.
Infect Immun ; 72(8): 4864-7, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15271949

RESUMO

luxS mutants of Borrelia burgdorferi strain 297 naturally colonized their arthropod (Ixodes scapularis) vector, were maintained in ticks throughout the molting process (larvae to nymphs), were tick transmitted to uninfected mice, and elicited histopathology in mice indistinguishable from that induced by wild-type B. burgdorferi.


Assuntos
Proteínas de Bactérias/genética , Borrelia burgdorferi/crescimento & desenvolvimento , Borrelia burgdorferi/patogenicidade , Ixodes/microbiologia , Doença de Lyme/transmissão , Animais , Mordeduras e Picadas , Borrelia burgdorferi/fisiologia , Liases de Carbono-Enxofre , Feminino , Doença de Lyme/microbiologia , Doença de Lyme/patologia , Camundongos , Camundongos Endogâmicos C3H , Mutação
11.
Infect Immun ; 71(5): 2892-6, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12704164

RESUMO

The luxS gene product is an integral component of LuxS/autoinducer-2 (AI-2) quorum-sensing systems in bacteria. A putative luxS gene was expressed at comparable levels by Borrelia burgdorferi strain 297 cultivated either in vitro or in dialysis membrane chambers implanted in rat peritoneal cavities. Although the borrelial luxS gene functionally complemented a LuxS deficiency in Escherichia coli DH5 alpha, AI-2-like activity could not be detected within B. burgdorferi culture supernatants or concentrated cell lysates. Finally, a luxS-deficient mutant of B. burgdorferi was infectious at wild-type levels when it was intradermally needle inoculated into mice, indicating that expression of luxS probably is not required for infectivity but, at the very least, is not essential for mammalian host adaptation. Our findings also challenge the notion that a LuxS/AI-2 quorum-sensing system is operative in B. burgdorferi.


Assuntos
Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Genes Bacterianos/fisiologia , Doença de Lyme/etiologia , Animais , Proteínas de Bactérias/fisiologia , Borrelia burgdorferi/patogenicidade , Liases de Carbono-Enxofre , Camundongos , Mutação , Agulhas , Óperon , Virulência
12.
Bioinformatics ; 19(13): 1718-9, 2003 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15593406

RESUMO

FindGDPs is a program that uses a greedy algorithm to quickly identify a set of genome-directed primers that specifically anneal to all of the open reading frames ina genome and that do not exhibit full-length complementarity to the members of another user-supplied set of nucleotide sequences.


Assuntos
Primers do DNA/análise , Genoma Bacteriano , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Software , Algoritmos , Sequência de Bases , DNA Bacteriano/análise , Genética Microbiana/instrumentação , Componentes Genômicos , Internet , Fases de Leitura Aberta , Design de Software , Interface Usuário-Computador
13.
Proc Natl Acad Sci U S A ; 99(3): 1562-7, 2002 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-11830671

RESUMO

DNA microarrays were used to survey the adaptive genetic responses of Borrelia burgdorferi (Bb) B31, the Lyme disease spirochete, when grown under conditions analogous to those found in unfed ticks (UTs), fed ticks (FTs), or during mammalian host adaptation (Bb in dialysis membrane chambers implanted in rats). Microarrays contained 95.4% of the predicted B31 genes, 150 (8.6%) of which were differentially regulated (changes of > or = 1.8-fold) among the three growth conditions. A substantial proportion (46%) of the differentially regulated genes encoded proteins with predicted export signals (29% from predicted lipoproteins), emphasizing the importance to Bb of modulating its extracellular proteome. For B31 cultivated at the more restrictive UT condition, microarray data provided evidence of a bacterial stringent response and factors that restrict cell division. A large proportion of genes were responsive to the FT growth condition, wherein increased temperature and reduced pH were prominent environmental parameters. A surprising theme, supported by cluster analysis, was that many of the gene expression changes induced during the FT growth condition were transient and largely tempered as B31 adapted to the mammalian host, suggesting that once Bb gains entry and adapts to mammalian tissues, fewer differentially regulated genes are exploited. It therefore would seem that although widely dissimilar, the UT and dialysis membrane chamber growth conditions promote more static patterns of gene expression in Bb. The microarray data thus provide a basis for formulating new testable hypotheses regarding the life cycle of Bb and attaining a more complete understanding of many aspects of Bb's complex parasitic strategies.


Assuntos
Borrelia burgdorferi/genética , Regulação Bacteriana da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Borrelia burgdorferi/crescimento & desenvolvimento , Borrelia burgdorferi/patogenicidade , Primers do DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Complementar , Genoma Bacteriano , Humanos , Doença de Lyme/microbiologia , Replicon , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carrapatos/microbiologia , Transcrição Gênica
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