Plasmodium vivax, un parasite pas si banal - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Stéphane PICOT - Hôpital E. Herriot, Lyon, France - picot@rockefeller.univ-lyon1.fr
The document discusses hepatitis B, including its epidemiology, transmission, clinical presentations, natural history, and virology. Some key points:
- Hepatitis B is endemic in many parts of Asia and Africa, with transmission primarily vertical or sexual.
- Acute hepatitis B often resolves on its own but can lead to chronic infection in 5-10% of cases.
- Chronic hepatitis B can take forms associated with wild type virus or pre-core mutants, and may progress to cirrhosis or liver cancer over decades.
- The virus replicates via an RNA intermediate and reverse transcription, forming cccDNA in the nucleus that maintains infection.
The document summarizes research on hepatitis C virus (HCV) resistance to treatments. It discusses three key points:
1. HCV can develop resistance to interferon-alpha and ribavirin treatment, as well as direct-acting antivirals (DAAs). Resistance is caused by genetic mutations in the virus.
2. Certain genetic variants of the host, particularly near the IL28B gene, influence treatment response by affecting interferon signaling and HCV kinetics.
3. New DAAs target various stages of the HCV life cycle including the NS3/4A protease, NS5B polymerase, and NS5A protein. While some DAAs have a low barrier to resistance,
The document discusses hepatitis C virus (HCV) resistance to different antiviral treatments. It finds that HCV resistance to interferon-alpha therapy exists but accounts for only a small portion of treatment failures. Resistance to ribavirin is unclear as its mechanism of action is not fully understood. Direct acting antivirals in development target various stages of the HCV life cycle and resistance can emerge through amino acid substitutions, but combination therapy aims to prevent resistance.
Triple combination treatment failures are associated with poor interferon responsiveness in patients and the presence of pre-existing resistant variants, such as Q80K, which can influence treatment outcomes. Treatment failures typically result in the selection of drug-resistant viruses, though protease inhibitor-resistant viruses are progressively replaced by wild-type viruses over time after treatment ends. In contrast, NS5A inhibitor-resistant viruses appear to persist longer. The presence of pre-existing resistance variants has only a modest impact on success rates of interferon-free regimens. While resistance is observed in some treatment failures with these regimens, overall response rates remain very high even in the presence of variants.
This downloadable slideset summarizes key studies selected by Andrew J. Muir, MD, David R. Nelson, MD, and Norah Terrault, MD, MPH, regarding the use of investigational agents for treating hepatitis C presented at the 2015 Annual Meeting of the European Association for the Study of the Liver.
Format: Microsoft PowerPoint (.ppt)
File size: 1.99 MB
This document discusses hepatitis C virus (HCV) resistance to treatments. It covers three main topics:
1. Resistance to interferon-alpha (IFN-α) and ribavirin treatment is common, especially for genotype 1 HCV infections. Viral factors like intrinsic properties and kinetics contribute to treatment failure and resistance.
2. HCV can develop resistance to direct-acting antivirals (DAAs) like protease inhibitors and polymerase inhibitors through amino acid substitutions. Resistance emerges from minor viral populations and affects drug efficacy.
3. Several new DAAs are in clinical trials, including protease inhibitors, nucleotide analogues, and non-nucleoside polymerase inhibitors. Their resistance profiles are being
Presentation 2.1 Update June 2016 on AHPND and EHP research in Thailand (Dr T...ExternalEvents
http://www.fao.org/documents/card/en/c/28b6bd62-5433-4fad-b5a1-8ac61eb671b1/
FAO Second International Technical Seminar/Workshop on Acute hepatopancreatic necrosis disease (AHPND) There is a way forward! FAO Technical Cooperation Programme: TCP/INT/3501 and TCP/INT/3502.
The document discusses hepatitis C virus (HCV) resistance to direct-acting antiviral (DAA) drugs. It finds that:
1) Baseline resistance-associated variants (RAVs) were detected in 15-27% of treatment-naive genotype 1 patients by deep sequencing, with higher prevalences in some regions.
2) The presence of certain RAVs at baseline was associated with reduced sustained virologic response (SVR) rates to some DAA regimens, particularly for NS5A inhibitors.
3) However, most patients with baseline RAVs still achieved SVR when treated with optimized, interferon-free combinations with or without ribavirin extension.
The document discusses hepatitis B, including its epidemiology, transmission, clinical presentations, natural history, and virology. Some key points:
- Hepatitis B is endemic in many parts of Asia and Africa, with transmission primarily vertical or sexual.
- Acute hepatitis B often resolves on its own but can lead to chronic infection in 5-10% of cases.
- Chronic hepatitis B can take forms associated with wild type virus or pre-core mutants, and may progress to cirrhosis or liver cancer over decades.
- The virus replicates via an RNA intermediate and reverse transcription, forming cccDNA in the nucleus that maintains infection.
The document summarizes research on hepatitis C virus (HCV) resistance to treatments. It discusses three key points:
1. HCV can develop resistance to interferon-alpha and ribavirin treatment, as well as direct-acting antivirals (DAAs). Resistance is caused by genetic mutations in the virus.
2. Certain genetic variants of the host, particularly near the IL28B gene, influence treatment response by affecting interferon signaling and HCV kinetics.
3. New DAAs target various stages of the HCV life cycle including the NS3/4A protease, NS5B polymerase, and NS5A protein. While some DAAs have a low barrier to resistance,
The document discusses hepatitis C virus (HCV) resistance to different antiviral treatments. It finds that HCV resistance to interferon-alpha therapy exists but accounts for only a small portion of treatment failures. Resistance to ribavirin is unclear as its mechanism of action is not fully understood. Direct acting antivirals in development target various stages of the HCV life cycle and resistance can emerge through amino acid substitutions, but combination therapy aims to prevent resistance.
Triple combination treatment failures are associated with poor interferon responsiveness in patients and the presence of pre-existing resistant variants, such as Q80K, which can influence treatment outcomes. Treatment failures typically result in the selection of drug-resistant viruses, though protease inhibitor-resistant viruses are progressively replaced by wild-type viruses over time after treatment ends. In contrast, NS5A inhibitor-resistant viruses appear to persist longer. The presence of pre-existing resistance variants has only a modest impact on success rates of interferon-free regimens. While resistance is observed in some treatment failures with these regimens, overall response rates remain very high even in the presence of variants.
This downloadable slideset summarizes key studies selected by Andrew J. Muir, MD, David R. Nelson, MD, and Norah Terrault, MD, MPH, regarding the use of investigational agents for treating hepatitis C presented at the 2015 Annual Meeting of the European Association for the Study of the Liver.
Format: Microsoft PowerPoint (.ppt)
File size: 1.99 MB
This document discusses hepatitis C virus (HCV) resistance to treatments. It covers three main topics:
1. Resistance to interferon-alpha (IFN-α) and ribavirin treatment is common, especially for genotype 1 HCV infections. Viral factors like intrinsic properties and kinetics contribute to treatment failure and resistance.
2. HCV can develop resistance to direct-acting antivirals (DAAs) like protease inhibitors and polymerase inhibitors through amino acid substitutions. Resistance emerges from minor viral populations and affects drug efficacy.
3. Several new DAAs are in clinical trials, including protease inhibitors, nucleotide analogues, and non-nucleoside polymerase inhibitors. Their resistance profiles are being
Presentation 2.1 Update June 2016 on AHPND and EHP research in Thailand (Dr T...ExternalEvents
http://www.fao.org/documents/card/en/c/28b6bd62-5433-4fad-b5a1-8ac61eb671b1/
FAO Second International Technical Seminar/Workshop on Acute hepatopancreatic necrosis disease (AHPND) There is a way forward! FAO Technical Cooperation Programme: TCP/INT/3501 and TCP/INT/3502.
The document discusses hepatitis C virus (HCV) resistance to direct-acting antiviral (DAA) drugs. It finds that:
1) Baseline resistance-associated variants (RAVs) were detected in 15-27% of treatment-naive genotype 1 patients by deep sequencing, with higher prevalences in some regions.
2) The presence of certain RAVs at baseline was associated with reduced sustained virologic response (SVR) rates to some DAA regimens, particularly for NS5A inhibitors.
3) However, most patients with baseline RAVs still achieved SVR when treated with optimized, interferon-free combinations with or without ribavirin extension.
This document summarizes the evolution of hepatitis C virus (HCV) treatment options from 1991 to 2014. It describes the progression from interferon-based regimens to the addition of direct-acting antivirals (DAAs), both first and second generation. It highlights results from clinical trials evaluating DAA combinations and all-oral interferon-free regimens. It also discusses factors like resistance, duration of response, the potential ongoing role of interferon, real-world effectiveness, and treatment of cirrhotic patients. The future of HCV therapy appears highly promising with short, well-tolerated, interferon-free options now available and in development.
In-vitro Correlates of Heterologous Protection using Avidity and IgG-Subtypin...EuFMD
The 2018 Open Session of the EuFMD Standing Technical Committee was held in Borgo Egnazia - Italy, 29-31 October 2018 . The session theme was on global vaccine security
The European Commission for the Control of Foot-and-Mouth Disease (EuFMD), one of FAO’s oldest Commissions, came into being on the 12th June 1954, with the pledge of the sixth founding member state to the principles of a coordinated and common action against Foot-and-mouth Disease.
This study evaluated an adenovirus vector (AdaPAscAb) expressing a single-chain antibody against anthrax protective antigen (PA) for passive immunotherapy against anthrax toxin. In vitro, AdaPAscAb expressed and secreted the anti-PA antibody, which specifically bound PA. Mice administered AdaPAscAb produced the antibody in their serum for up to 14 days. Mice treated with AdaPAscAb were fully protected from lethal anthrax toxin challenge 72 hours later, whereas control mice were not protected. While effective, the antibody's half-life was too short for human use; further engineering is needed to extend its circulation time.
Role of neutralizing antibodies in covid 19PathKind Labs
1) Studies on rhesus monkeys found that those who were re-exposed to SARS-CoV-2 after recovering from initial infection did not experience disease recurrence or viral replication, demonstrating protection from reinfection by neutralizing antibodies.
2) Vaccine trials show that neutralizing antibodies induced by mRNA vaccines effectively neutralize emerging variants like B.1.351, and a single vaccine dose can generate neutralizing antibodies in previously infected individuals.
3) The level of neutralizing antibodies required for protection against SARS-CoV-2 in rhesus macaques was found to be 50, with higher RBD and spike IgG titers also correlating with protection.
Clinical Impact of New Data From AASLD 2015hivlifeinfo
In this downloadable slideset, David R. Nelson, MD, and Norah Terrault, MD, MPH, review key HCV studies presented at the 2015 Annual Meeting of the European Association for the Study of the Liver.
Format: Microsoft PowerPoint (.ppt)
File size: 2.19 MB
Date posted: 12/2/2015
1) The study examined CD4+ T cells in the central nervous system (CNS) of mice during experimental allergic encephalomyelitis (EAE), both during active disease and remission.
2) Flow cytometry analysis revealed a 30-fold reduction in the number of CD4+ T cells in the CNS of mice in remission compared to those with active EAE.
3) However, the CD4+ T cells that remained in the CNS during remission maintained an activated memory/effector phenotype, suggesting remission is not due to downregulation of T cell function.
EFV has a low resistance barrier and its toxicity has been underestimated due to a high prevalence of slow metabolizers in South Africa. Dolutegravir is an attractive alternative to EFV for first-line ART due to its high resistance barrier, which means fewer switches to second-line treatment. Lopinavir/ritonavir may not be the best choice for second-line ART; atazanavir/ritonavir or darunavir/ritonavir are better tolerated but require pharmacokinetic studies of adjusted doses with rifampicin. Tenofovir alafenamide has fewer toxic effects than tenofovir disoproxil fumarate and similar efficacy
This document summarizes the natural history of hepatitis B virus (HBV) infection. It describes how acute HBV infection can resolve or progress to chronic infection in 5-10% of cases. Chronic HBV infection can take several forms including infection with the wild-type virus (HBeAg positive) or pre-core mutants (HBeAg negative). Without treatment, chronic HBV can lead to cirrhosis or hepatocellular carcinoma over 30-50 years.
This document summarizes a presentation on hepatitis C virus (HCV) natural history and therapeutics by Dr. Alnoor Ramji. It discusses how HCV has a slowly progressive course that can lead to cirrhosis and complications like liver cancer. New all-oral drug regimens are highly effective, achieving viral eradication rates of 70-98%, and viral eradication improves mortality outcomes. The presentation reviews HCV genotypes and disease progression, outlines improvements in treatment efficacy over time, and discusses side effects and outcomes of newer protease inhibitor and nucleotide/nucleoside analog regimens.
David Wyles, M.D., of the UC San Diego AntiViral Research Center, presents "HCV in 2015: New Medication Approvals and Innovative Studies...Including a One-Shot Cure?" at AIDS Clinical Rounds
This document provides an overview of new oral medications for treating hepatitis C virus (HCV) infection, including NS3/4A protease inhibitors telaprevir and boceprevir. It discusses HCV genotypes and lifecycle, focusing on improved understanding of viral targets leading to drug discovery. NS3/4A protease inhibitors and NS5B polymerase inhibitors currently in clinical development are described, targeting polyprotein processing and HCV replication respectively. Nucleoside and non-nucleoside NS5B inhibitors as well as NS5A inhibitors and their mechanisms of action and clinical trial status are summarized.
This document summarizes research into the toxicity of the pesticide dieldrin. Experiments showed that dieldrin exposure leads to oxidative stress, mitochondrial dysfunction, and activation of caspase enzymes and pro-apoptotic proteins PKCδ and PARP in dopaminergic neural cells. This triggers cellular apoptosis and DNA fragmentation, demonstrating that dieldrin causes neurodegeneration through inducing programmed cell death pathways.
Antimicrob. agents chemother. 2015-lee-aac.01477-15NAIF AL SAGLAN
This document summarizes a study comparing clinical outcomes of patients with Enterobacter cloacae bacteremia treated definitively with cefepime or carbapenems. The study found:
1) Among 144 patients receiving definitive cefepime or carbapenem therapy, 30-day mortality rates were similar at 26.4% for cefepime and 22.2% for carbapenems.
2) However, for the 18 patients infected with cefepime susceptible-dose dependent (SDD) isolates, those treated with cefepime had a higher 30-day mortality rate than those treated with carbapenems (71.4% vs 18.2%).
3
HIV persists within the body despite successful suppression of virus replication with antiretroviral therapy (ART). HIV lurks in latent and active reservoirs, leading to rebound of virus spread if ART is interrupted. The latent HIV reservoir is a natural consequence of the lifecycle of HIV, with integration of HIV into the genomes of cells that are or later enter the resting state, resulting in transcriptionally quiescent provirus. Resting CD4 T cells comprise the majority of the latent reservoir. Multiple factors such as the degree of virus exposure, timing of ART, and host factors can influence the size and characteristics of the HIV reservoir. Constructing and testing effective strategies for HIV eradication and measuring their impact will require a sophisticated knowledge of the HIV reservoir, detailed understanding of the antiviral immune response, and of the diversity and kinetics of the latent viral reservoir.
The document summarizes information about HIV, its life cycle, approved antiretroviral drugs, adverse effects of antiretrovirals, lipodystrophy, drug interactions, and guidelines for initiating antiretroviral therapy in special populations. It provides details on the classes of antiretrovirals including nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, CCR5 antagonists. It discusses the rationale for combination antiretroviral therapy and boosted protease inhibitors.
Sebastiani Gian Domenico Torino 13° Convegno Patologia Immune E Malattie Orfa...cmid
This document discusses the use of rituximab to treat lupus erythematosus systemic (LES). It describes rituximab as a monoclonal antibody that targets and eliminates CD20-positive B cells. B cells play a role in LES by producing autoantibodies and cytokines. The document reviews several studies on rituximab for LES, including retrospective analyses showing improvements in disease activity scores and safety, and randomized controlled trials like EXPLORER and LUNAR that did not show statistically significant superiority of rituximab over standard therapies. It notes differences between study populations and real-world patients treated with rituximab. The conclusion is that rituximab appears effective for
This document discusses drug resistant tuberculosis (TB) and recent updates in diagnostics and management. It covers the different types of drug resistant TB like mono, poly, MDR, XDR, and TDR. India has an estimated 3% prevalence of MDR-TB among new cases and 12-17% among previously treated cases. Diagnosis of drug resistant TB involves tests like culture, Xpert MTB/RIF, and line probe assays (LPA). Newer versions of tests like Xpert and LPA have increased sensitivity. Proper diagnosis is important for treatment, with principles including treating according to drug susceptibility testing to improve outcomes.
This document discusses seizures in pediatrics, including neonatal seizures, febrile seizures, status epilepticus, and epileptic syndromes. It provides information on etiology, clinical presentation, diagnostic evaluation with EEG, imaging and labs, and treatment with antiepileptic drugs. Causes of seizures in newborns include hypoxic-ischemic encephalopathy, infections, hemorrhage, and metabolic derangements. Febrile seizures typically occur between 3 months and 5 years of age and are usually self-limited. Status epilepticus is defined as continuous seizure activity or recurrent seizures without regaining consciousness lasting over 30 minutes.
This document discusses a case of ventilator-associated pneumonia (VAP) in a long-term ventilated patient. It provides details on the patient's history, exam findings, labs, imaging and treatment. VAP is a common ICU infection that occurs in intubated patients after 48 hours of mechanical ventilation. Risk factors include prolonged ventilation, comorbidities, and host factors. Treatment involves empiric antibiotics targeted against likely pathogens based on onset and institutional epidemiology. Prevention strategies center around a multidisciplinary VAP bundle approach.
This document discusses a case of ventilator-associated pneumonia (VAP) in a long-term ventilated patient. It provides details on the patient's history, examination findings, investigations, and treatment. VAP is a common nosocomial infection in the ICU that occurs within 48 hours of mechanical ventilation. Prolonged ventilation increases the risk of developing VAP. The document reviews risk factors, pathogenesis, diagnosis, treatment and prevention of VAP.
This document summarizes the evolution of hepatitis C virus (HCV) treatment options from 1991 to 2014. It describes the progression from interferon-based regimens to the addition of direct-acting antivirals (DAAs), both first and second generation. It highlights results from clinical trials evaluating DAA combinations and all-oral interferon-free regimens. It also discusses factors like resistance, duration of response, the potential ongoing role of interferon, real-world effectiveness, and treatment of cirrhotic patients. The future of HCV therapy appears highly promising with short, well-tolerated, interferon-free options now available and in development.
In-vitro Correlates of Heterologous Protection using Avidity and IgG-Subtypin...EuFMD
The 2018 Open Session of the EuFMD Standing Technical Committee was held in Borgo Egnazia - Italy, 29-31 October 2018 . The session theme was on global vaccine security
The European Commission for the Control of Foot-and-Mouth Disease (EuFMD), one of FAO’s oldest Commissions, came into being on the 12th June 1954, with the pledge of the sixth founding member state to the principles of a coordinated and common action against Foot-and-mouth Disease.
This study evaluated an adenovirus vector (AdaPAscAb) expressing a single-chain antibody against anthrax protective antigen (PA) for passive immunotherapy against anthrax toxin. In vitro, AdaPAscAb expressed and secreted the anti-PA antibody, which specifically bound PA. Mice administered AdaPAscAb produced the antibody in their serum for up to 14 days. Mice treated with AdaPAscAb were fully protected from lethal anthrax toxin challenge 72 hours later, whereas control mice were not protected. While effective, the antibody's half-life was too short for human use; further engineering is needed to extend its circulation time.
Role of neutralizing antibodies in covid 19PathKind Labs
1) Studies on rhesus monkeys found that those who were re-exposed to SARS-CoV-2 after recovering from initial infection did not experience disease recurrence or viral replication, demonstrating protection from reinfection by neutralizing antibodies.
2) Vaccine trials show that neutralizing antibodies induced by mRNA vaccines effectively neutralize emerging variants like B.1.351, and a single vaccine dose can generate neutralizing antibodies in previously infected individuals.
3) The level of neutralizing antibodies required for protection against SARS-CoV-2 in rhesus macaques was found to be 50, with higher RBD and spike IgG titers also correlating with protection.
Clinical Impact of New Data From AASLD 2015hivlifeinfo
In this downloadable slideset, David R. Nelson, MD, and Norah Terrault, MD, MPH, review key HCV studies presented at the 2015 Annual Meeting of the European Association for the Study of the Liver.
Format: Microsoft PowerPoint (.ppt)
File size: 2.19 MB
Date posted: 12/2/2015
1) The study examined CD4+ T cells in the central nervous system (CNS) of mice during experimental allergic encephalomyelitis (EAE), both during active disease and remission.
2) Flow cytometry analysis revealed a 30-fold reduction in the number of CD4+ T cells in the CNS of mice in remission compared to those with active EAE.
3) However, the CD4+ T cells that remained in the CNS during remission maintained an activated memory/effector phenotype, suggesting remission is not due to downregulation of T cell function.
EFV has a low resistance barrier and its toxicity has been underestimated due to a high prevalence of slow metabolizers in South Africa. Dolutegravir is an attractive alternative to EFV for first-line ART due to its high resistance barrier, which means fewer switches to second-line treatment. Lopinavir/ritonavir may not be the best choice for second-line ART; atazanavir/ritonavir or darunavir/ritonavir are better tolerated but require pharmacokinetic studies of adjusted doses with rifampicin. Tenofovir alafenamide has fewer toxic effects than tenofovir disoproxil fumarate and similar efficacy
This document summarizes the natural history of hepatitis B virus (HBV) infection. It describes how acute HBV infection can resolve or progress to chronic infection in 5-10% of cases. Chronic HBV infection can take several forms including infection with the wild-type virus (HBeAg positive) or pre-core mutants (HBeAg negative). Without treatment, chronic HBV can lead to cirrhosis or hepatocellular carcinoma over 30-50 years.
This document summarizes a presentation on hepatitis C virus (HCV) natural history and therapeutics by Dr. Alnoor Ramji. It discusses how HCV has a slowly progressive course that can lead to cirrhosis and complications like liver cancer. New all-oral drug regimens are highly effective, achieving viral eradication rates of 70-98%, and viral eradication improves mortality outcomes. The presentation reviews HCV genotypes and disease progression, outlines improvements in treatment efficacy over time, and discusses side effects and outcomes of newer protease inhibitor and nucleotide/nucleoside analog regimens.
David Wyles, M.D., of the UC San Diego AntiViral Research Center, presents "HCV in 2015: New Medication Approvals and Innovative Studies...Including a One-Shot Cure?" at AIDS Clinical Rounds
This document provides an overview of new oral medications for treating hepatitis C virus (HCV) infection, including NS3/4A protease inhibitors telaprevir and boceprevir. It discusses HCV genotypes and lifecycle, focusing on improved understanding of viral targets leading to drug discovery. NS3/4A protease inhibitors and NS5B polymerase inhibitors currently in clinical development are described, targeting polyprotein processing and HCV replication respectively. Nucleoside and non-nucleoside NS5B inhibitors as well as NS5A inhibitors and their mechanisms of action and clinical trial status are summarized.
This document summarizes research into the toxicity of the pesticide dieldrin. Experiments showed that dieldrin exposure leads to oxidative stress, mitochondrial dysfunction, and activation of caspase enzymes and pro-apoptotic proteins PKCδ and PARP in dopaminergic neural cells. This triggers cellular apoptosis and DNA fragmentation, demonstrating that dieldrin causes neurodegeneration through inducing programmed cell death pathways.
Antimicrob. agents chemother. 2015-lee-aac.01477-15NAIF AL SAGLAN
This document summarizes a study comparing clinical outcomes of patients with Enterobacter cloacae bacteremia treated definitively with cefepime or carbapenems. The study found:
1) Among 144 patients receiving definitive cefepime or carbapenem therapy, 30-day mortality rates were similar at 26.4% for cefepime and 22.2% for carbapenems.
2) However, for the 18 patients infected with cefepime susceptible-dose dependent (SDD) isolates, those treated with cefepime had a higher 30-day mortality rate than those treated with carbapenems (71.4% vs 18.2%).
3
HIV persists within the body despite successful suppression of virus replication with antiretroviral therapy (ART). HIV lurks in latent and active reservoirs, leading to rebound of virus spread if ART is interrupted. The latent HIV reservoir is a natural consequence of the lifecycle of HIV, with integration of HIV into the genomes of cells that are or later enter the resting state, resulting in transcriptionally quiescent provirus. Resting CD4 T cells comprise the majority of the latent reservoir. Multiple factors such as the degree of virus exposure, timing of ART, and host factors can influence the size and characteristics of the HIV reservoir. Constructing and testing effective strategies for HIV eradication and measuring their impact will require a sophisticated knowledge of the HIV reservoir, detailed understanding of the antiviral immune response, and of the diversity and kinetics of the latent viral reservoir.
The document summarizes information about HIV, its life cycle, approved antiretroviral drugs, adverse effects of antiretrovirals, lipodystrophy, drug interactions, and guidelines for initiating antiretroviral therapy in special populations. It provides details on the classes of antiretrovirals including nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, CCR5 antagonists. It discusses the rationale for combination antiretroviral therapy and boosted protease inhibitors.
Sebastiani Gian Domenico Torino 13° Convegno Patologia Immune E Malattie Orfa...cmid
This document discusses the use of rituximab to treat lupus erythematosus systemic (LES). It describes rituximab as a monoclonal antibody that targets and eliminates CD20-positive B cells. B cells play a role in LES by producing autoantibodies and cytokines. The document reviews several studies on rituximab for LES, including retrospective analyses showing improvements in disease activity scores and safety, and randomized controlled trials like EXPLORER and LUNAR that did not show statistically significant superiority of rituximab over standard therapies. It notes differences between study populations and real-world patients treated with rituximab. The conclusion is that rituximab appears effective for
This document discusses drug resistant tuberculosis (TB) and recent updates in diagnostics and management. It covers the different types of drug resistant TB like mono, poly, MDR, XDR, and TDR. India has an estimated 3% prevalence of MDR-TB among new cases and 12-17% among previously treated cases. Diagnosis of drug resistant TB involves tests like culture, Xpert MTB/RIF, and line probe assays (LPA). Newer versions of tests like Xpert and LPA have increased sensitivity. Proper diagnosis is important for treatment, with principles including treating according to drug susceptibility testing to improve outcomes.
This document discusses seizures in pediatrics, including neonatal seizures, febrile seizures, status epilepticus, and epileptic syndromes. It provides information on etiology, clinical presentation, diagnostic evaluation with EEG, imaging and labs, and treatment with antiepileptic drugs. Causes of seizures in newborns include hypoxic-ischemic encephalopathy, infections, hemorrhage, and metabolic derangements. Febrile seizures typically occur between 3 months and 5 years of age and are usually self-limited. Status epilepticus is defined as continuous seizure activity or recurrent seizures without regaining consciousness lasting over 30 minutes.
This document discusses a case of ventilator-associated pneumonia (VAP) in a long-term ventilated patient. It provides details on the patient's history, exam findings, labs, imaging and treatment. VAP is a common ICU infection that occurs in intubated patients after 48 hours of mechanical ventilation. Risk factors include prolonged ventilation, comorbidities, and host factors. Treatment involves empiric antibiotics targeted against likely pathogens based on onset and institutional epidemiology. Prevention strategies center around a multidisciplinary VAP bundle approach.
This document discusses a case of ventilator-associated pneumonia (VAP) in a long-term ventilated patient. It provides details on the patient's history, examination findings, investigations, and treatment. VAP is a common nosocomial infection in the ICU that occurs within 48 hours of mechanical ventilation. Prolonged ventilation increases the risk of developing VAP. The document reviews risk factors, pathogenesis, diagnosis, treatment and prevention of VAP.
Polymorphisme parasitaire et accès graves en zone périurbaine - Conférence de la 5e édition du Cours international « Atelier Paludisme » - Ronan JAMBOU - Institut Pasteur de Dakar - rjambou@pasteur.sn
Current status of Malaria vaccine (Nov 2016)Pranav Sopory
This document summarizes information about the current status of malaria vaccines. It discusses the burden of malaria worldwide and in India. It describes the life cycle of Plasmodium parasites and the different types of malaria. The key targets for malaria vaccines including pre-erythrocytic, blood stage, and transmission blocking vaccines are outlined. The currently available RTS,S vaccine is described including results from phase 3 trials showing moderate efficacy that wanes over time. Challenges in developing effective malaria vaccines are discussed such as applying traditional vaccine approaches, limitations of animal models, and waning vaccine efficacy. New malaria vaccine projects in India including JAIVAC-1 and JAIVAC-2 are briefly introduced.
- Neonatal seizures, febrile seizures, CNS infections, and strokes are common neurological conditions seen in pediatrics.
- Common etiologies of neonatal seizures include hypoxic-ischemic encephalopathy, congenital CNS anomalies, intracranial hemorrhage, and electrolyte or metabolic abnormalities.
- Evaluation involves history, physical exam, lab studies, and neuroimaging like EEG, ultrasound, CT, or MRI depending on the situation.
- Treatment involves anticonvulsants tailored to the specific condition, with phenobarbital, phenytoin, and lorazepam as first line options for status epilepticus.
Chelonian diagnostics, pathology and treatmentmgray11
This document summarizes a presentation on ranavirus epidemiology, diagnostics, and treatment in chelonians. Key points include:
- Ranavirus disease events often occur in local epizootics and some locations see annual outbreaks.
- Quantitative PCR was developed to detect ranavirus using a 54 bp segment of the major capsid protein gene.
- A study found a 1.5% prevalence of ranavirus in free-living and rehabilitation chelonian populations.
- An experimental study found higher mortality from ranavirus infection in red-eared sliders housed at 22°C compared to 28°C, indicating environmental temperature impacts disease outcome.
Gene Olinger, USAMRIID, Fort Detrick USA, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Protective Immune Reponses to Ebola Virus
STD Prevalence in World, USA and Iran, and Neisseria gonorrhoeaeMeisam Ruzbahani
The document discusses sexually transmitted infections (STIs). It provides lists of common bacterial, fungal, viral and parasitic infections including Neisseria gonorrhoeae, Chlamydia trachomatis, HIV, HPV, and Trichomonas vaginalis. It notes that STIs can cause complications like pelvic inflammatory disease and increase the risk of HIV transmission. Global statistics on new curable STI cases are provided, with the highest numbers in South and Southeast Asia. The document also discusses how STIs differently impact women, including increased risk of infertility and passing infections to babies.
- A 49-year-old female presented with altered sensorium, vomiting, and one seizure. Examination found neck stiffness and positive Brudzinski sign.
- Laboratory findings showed abnormal liver enzymes, electrolytes, coagulation markers, and thyroid function. Cerebrospinal fluid analysis found elevated proteins and low glucose.
- She was diagnosed with acute pyogenic meningitis, likely caused by Streptococcus pneumoniae based on her age. She received ceftriaxone, vancomycin, dexamethasone and other supportive treatments.
Presentation by adrian hill [university of oxford]Pamoja
Malaria is a major global health problem, killing over 700,000 people annually. Developing an effective vaccine is challenging due to the parasite's complex life cycle and ability to evade the immune system. Current vaccine approaches include protein-adjuvant vaccines targeting specific stages, viral vectored vaccines to induce cellular immunity, and whole parasite vaccines. Significant progress has been made, but partial efficacy has required unprecedented immunogenicity. A multi-component vaccine targeting multiple stages may be needed for high efficacy.
This document discusses acute bacterial meningitis (BM), including its definition, incidence, risk factors, etiology, clinical presentation, diagnosis, treatment goals and principles, specific treatment recommendations for common causative organisms, prevention through vaccination, and outpatient management considerations. The prognosis of untreated BM is poor, with high treatment failure rates and risk of neurological complications; however, prompt administration of appropriate antibiotic therapy can significantly improve outcomes.
This document discusses febrile neutropenia in a patient with acute myeloid leukemia (AML) who has recently undergone chemotherapy. The patient presents with a fever of 38°C. Key details include that the patient's absolute neutrophil count (ANC) is very low at 0.7 with 38% segments and 2% bands, indicating severe neutropenia. Management of febrile neutropenia depends on risk stratification based on factors like neutrophil count, expected duration of neutropenia, and presence of comorbidities. Initial evaluation includes blood cultures, screening for potential infection sites, and empiric intravenous antibiotics.
Bacterial meningitis remains a serious disease in adults, with S. pneumoniae and N. meningitidis causing the majority of cases. The initial approach involves assessing for the classic triad of symptoms, but lumbar puncture may be deferred if neuroimaging is warranted due to concerns for mass lesions or decreased consciousness. Empiric antibiotic therapy should begin as soon as possible, often in combination with vancomycin and dexamethasone, which reduces mortality and morbidity when given early in treatment. Outcomes depend on severity of symptoms and causative organism, with pneumococcal meningitis carrying the highest fatality and long-term complication rates.
This document summarizes a presentation on recurrent respiratory papillomatosis (RRP) including its causes, characteristics, treatment challenges, and areas of ongoing research. RRP is caused by HPV types 6 and 11 and frequently recurs due to activation of latent viral infection. While irradiation increases cancer risk, photodynamic therapy and celecoxib are being studied to control disease recurrence by improving immune response against latent HPV infection. Future research focuses on regulating latent infection and host immune responses.
1) The document provides an overview of malaria including epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment and prevention.
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Similar to Plasmodium vivax, un parasite pas si banal (20)
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Monitoring and Evaluation Toolkit - Séances Pratiques de la 5e édition du Cours international « Atelier Paludisme » - Luciano TUSEO - World Health Organization / Roll Back Malaria - Office for Madagascar and Reunion - Antananarivo, Madagascar - maloms@iris.mg
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- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
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Plasmodium vivax, un parasite pas si banal
1. Plasmodium vivax,
un parasite pas si banal
Université Claude Bernard - Faculté de Médecine
Equipe d’accueil - IFR des Neurosciences
Radicaux libres, substrats énergétiques et physiopathologie cérébrale
Lyon - France
Université Claude Bernard - Faculté de Médecine
Equipe d’accueil - IFR des Neurosciences
Radicaux libres, substrats énergétiques et physiopathologie cérébrale
Lyon - France
2. Vivax malaria paradigm
Benign tertian fever
Drug sensitive
Easily controlled
Malariatherapy
Wagner von Jauregg : 1917
Syphilis (treponema pallidum)
Plasmodium vivax
5-1Oml blood from malaria patient
8 to 12 malaria crisis …
5 % death
3. Transmissibilité de P. vivax
• P. vivax :
– Cycle anophélien en 10 jours environ à 30°C (Pf:13j)
– Jusqu’à 15°C (Pf: 18°C)
• Stades hépatiques
– 1 « lot » de schizontes hépatiques
– 1 « lot » d’hypnozoïtes
• Périodicité de libération des hypnozoïtes
adaptée au climat local
– reviviscence
4. Définitions
• Reviviscence (relapse) : nouveau cycle érythrocytaire à
partir de la libération de mérozoïtes provenant de
schizontes hépatiques primaires
• Recrudescence (recrudescence) : réapparition d'une
parasitémie détectable à la suite d'une résistance au
traitement
• Rechute (relapse) : accès clinique secondaire, à distance
du premier épisode, pour lequel l'origine des parasites
est difficile à mettre en évidence (rupture
d'hypnozoïtes ou formes érythrocytaires résistantes au
traitement)
6. Duffy Antigen receptor for Chemokines
(DARC)
• P. vivax et P. knowlesi
• Interaction de « Duffy-binding-like domain » (DBL) avec
le récepteur DARC.
• Polymorphisme de PvDARC (Papouasie-Nouvelle-Guinée,
Colombie)
• famille des DBLs : PfEMP1 (cytoadhérence)
• DARC est absent chez la plupart des populations noires
d’Afrique.
• P. vivax est présent :
– les peuples berbéroïdes (touaregs et maures) autour du Sahara
– les éthiopiens d’origine yéménite,
– les malgaches d’origine indonésienne
– les bushmen d’Afrique de l’est (Kalahari,Tanzanie) et du sud
8. benign tertian fever ?
The Ghost of the swamp
« The ghost of a man, a sufferer from his cradle to his grave,
aged even in childhood and laying down in misery that life
which was but one disease »
John Maccinlloch, 1827
Pernicious complications
Acute respiratory distress syndrome (Tanios 2001, Lawn 2003)
Cerebral malaria (Beg 2002)
Acute disseminated encephalomyelitis (Koibuchi 2003)
Retinal haemorrhages (Choi 2004)
9. Formes cliniques graves
• Pas de séquestration, Pas d’hyperparasitémie
– Mécanismes ?
• Atteinte Pulmonaires : SDRA
• Atteinte cérébrale
• Hémorragies rétiniennes
• Rupture de rate
• Anémie sévère
10. P. vivax: drug sensitive parasite ?
• Standard first choice drug: chloroquine
• Chloroquine resistance since 1989
19891990
1995
1995
1991
1995
11. P. vivax: drug sensitive parasite ?
• Supposed to be intrinsically resistant to sulfadoxine-
pyrimethamine
➪ Role of falciparum/vivax co-infection in Thaïlande
• Hypnozoïtes clearance by primaquine
➪ Decrease in primaquine efficacy (Indonesia, PNG,
Thailande)
➪ Prophylaxis failure
– Atovaquone-proguanil: Ethiopia (Povinelli & al 2003)
– Mefloquine : French Guyana (Picot & al. 2005)
12. Easy to detect vivax drug resistance ?
• Therapeutic efficacy tests
– WHO protocols
– Relapse patterns
– Scarcity of data
• In vitro tests
– Culture of P. vivax
– Few studies and few labs.
• Molecular markers
– Available for sulfadoxine-pyrimethamine and amino-4-quinoleines
– Blood spots easy to obtain
– Real time PCR highly efficient and reproducible
14. Pvmdr1 GenBank : AY618622
one exon (4392 nucleotides) 1464 aa
68% homology P. falciparum mdr1
P. vivax chloroquine resistance
Plasmodium falciparum
pfcrt
pfmdr1
Plasmodium vivax
pvcg10
Pvmdr1
15. Mutations ponctuelles conférant
la CQR chez P. falciparum
GAT
Asp/D
AAT
Asn/N
1042
TTA
Leu/L
1039
TAT
Tyr/Y
GAT
Asp/D
1246
TGT
Cys/C
AGT
Ser/S
1034
TAT
Tyr/Y
940
TTT
Phe/F
TAT
Tyr/Y
184
TAT
Tyr/Y
AAT
Asn/N
86
CQRCQSPositions AA
Pfmdr1
AAC
Asn/N
1079
CTT
Leu/L
TTT
Phe/F
1076
GAT
Asp/D
1291
AGT
Ser/S
1071
TTC/TTT
Phe/F
TAC
Tyr/Y
976
TAC
Tyr/Y
189
AAC
Asn/N
91
CQRCQSPositions AA
Pvmdr1
= site de mutation
TM = Transmembranaire
II° fragment amplifié
ATPTM TM
I° fragment amplifié
ATP
Mutations ponctuelles conférant
la CQR chez P. vivax
17. Usage des codons
• A+T : 15% moins élevé que P. falciparum
• Codon préféré : 3° base
– 100 % A/T : P. falciparum
– 50 % A/T : P. vivax
• AA les plus fréquents pour les protéines :
– P vivax : Lys, Glu, Leu, Ser
– P. falciparum : Asn, Glu, Leu
18. The association of mutations in Plasmodium vivax dhfr and mdr1 and in vivo
resistance to amodiaquine or chloroquine plus sulphadoxine-pyrimethamine in
Papua New Guinea
Jutta Marfurt1
, Frédérique de Monbrison2
, Sara Brega2
, Laetitia Barbollat2
, Ivo Müller3
, John C.
Reeder3
, Hans-Peter Beck1
, Stéphane Picot2
, Blaise Genton1*
Children between 6 months and 7 years of age
axillary temperature ≥37.5°C or history of fever during the last 48 hours
and microscopically confirmed monoinfection with P. vivax (density >250 /microlitre).
Absence of danger signs for severe or complicated malaria, signs of any other
disease, malnutrition or anaemia.
Standard AQ or CQ plus SP first-line treatment
(10 mg chloroquine or amodiaquine per kg on Day 0, 1 and 2, and 25 mg sulphadoxine
per kg plus 1.25 mg pyrimethamine per kg on Day 0)
Follow-up visits were done on Day 1, 2, 3, 7, 14, and 28.
Treatment failure :
5 mg artesunate per kg on Day 1 followed by 2.5 mg artesunate per kg on Day 2 to 7,
and a single dose of 25 mg sulphadoxine per kg plus 1.25 mg pyrimethamine per kg
on Day 3)
19. Study site
N orth C oast
area
(M adang
Province)
K arim ui
area
(Sim bu
Province)
South W osera
area
(East Sepik
Province)
Total
C haracteristics n=34 n=43 n=27 n=104
W eight (m ean (95% C I), kg)
15.9 (8.0-
23.8)
13.7 (12.2-
15.2)
12.0 (10.6-
13.5)
14.1 (11.2-
16.9)
A ge (m ean (95% C I), yrs) 2.3 (1.9-2.7)
3.5 (3.0-
4.0)
3.2 (2.5-3.9)
3.0 (2.7-
3.4)
Sex: fem ales/n (% ) 20 (58.8) 17 (39.5) 9 (36.0) 47 (45.2)
Tem perature (m ean (95% C I),°C )
37.1 (36.6-
37.6)
38.6 (38.3-
38.8)
37.0 (36.4-
37.6)
37.7 (37.4-
38.0)
H aem oglobin (m ean (95% C I), g/dl)
10.2 (9.4-
11.0)
10.6 (10.0-
11.2)
9.2 (8.6-9.8)
10.1 (9.7-
10.5)
Parasite density (geom etric m ean
(range), per µl)
4677 (300-
41280)
3437 (40-
36600)
4964 (160-
50640)
4182 (40-
50640)
C lass no (% )
A dequate clinical and parasitological
response (A C PR )
24 (70.6) 40 (93.0) 27 (100) 91 (87.5)
Treatm ent failure (TF) 10 (29.4) 3 (7.0) 0 (0) 13 (12.5)
23. Easy to treat vivax malaria ?
1. Standard treatment
2. Moderate drug resistance area (Thaïlande)
3. High risk of drug resistance area (Indonesia, PNG)
Check for G-6-PD status before primaquine, or forget it
24. Primaquine : 0.50 mg/kg/j, 14 jours
- LARIAM (250 mg)
2 cp / day, 1 day
- Primaquine (cp à 7.5 mg)
4 cp/day x 14 jours
Mefloquine : 15 mg/kg, dose unique
Contamination in high risk resistance area (Indonesia, PNG)
2 - Primaquine
0.50 mg/kg/j,
14 jours
- Chloroquine (100mg)
6 cp day 1, 6 cp day 2, 3 cp day 3
- Primaquine (cp à 7.5 mg)
4 cp/day x 14 jours
1 – Chloroquine
dose totale : 25 mg/kg/3jours.
Soit J1 : 10mg/kg ; J2 : 10 mg/kg, J3 : 5
mg/kg
Contamination in low chloroquine sensitive area (Thaïlande)
2 - Primaquine
0.25 mg/kg/d,
14 days
- Chloroquine (100mg)
6 cp day 1, 6 cp day 2, 3 cp day 3
- Primaquine (7.5 mg)
2 cp/day x 14 days
1 – Chloroquine
Total dose: 25 mg/kg/3 days.
D1 : 10mg/kg ; D2 : 10 mg/kg, D3 : 5
mg/kg
Contamination in chloroquine sensitive area:
patient 60 kg bw. G6PD test normalTreatment
25. Background on G6PD
• G6PD: pentose phosphate pathway, converts NADP+ to NADPH
• G6PD deficiency is a sex-linked genetic disorders, with full
expression in males
• Persons who are G6PD deficient are at increased risk for
experiencing hemolytic anemia when taking primaquine
• Primaquine is the only drug available that kills liver stage parasites
to prevent late malaria relapse in Plasmodium vivax, ovale
Adapted from Dennis Shanks, US army
(A - ) Variant affects approximately 10% of African Americans
Enzyme usually >10% normal
(B - ) Variant (MED) is the most common type affecting people from
Eastern Mediterranean
Enzyme usually <10% of normal
G6PD Genetic Variants
26. Mediterranean (B-) Variants
• Serious hemolysis can occur following one dose
of 15 mg primaquine base
• Patient may require blood transfusion often
hemolyzing > 50% erythrocytes
• Complications include:
– Acute Renal Failure
– High Output Cardiac Failure
– Anoxia and Death
27. The frequency of the (B-) variant differs
markedly among different populations
Caucasian 0.4%
Italians 0.5-1.0%
Hispanic 0.9%
Greek 2-9%
Sardinians 3-35%
Asian 1.8%
African American 7.6%
29. Asymptomatic patient,
Long stay in high risk area
(PNG), index case
G6PD normal
Minimun dose in unknown
G6PD normal
Atovaquone/proguanil
(duration of stay + 7 days
after return)
Systematic treatment with
primaquine after return
15 mg/14 days
double dose from PNG
Primaquine 30 mg/day (0.5
mg/kg/j) :
1-2 days before stay, every
day, + 7 days after
Doxycycline, mefloquine
(duration of stay + 28 days
after return
Do NOT forget P. falciparum
chemoprophylaxis in case
of mixed transmission area
Do NOT forget P.
falciparum
chemoprophylaxis in case
of mixed transmission area
No action against
hypnozoïtes and relapses
Activity against hypnozoïtesActivity againts primary
liver schizontes and
hypnozoïtes
Activity against erythrocytic
stages
Terminal
Prophylaxis
Causal
Prophylaxis
Suppressive
Prophylaxis
30. vivax malaria paradigm
Benign tertian fever
Drug sensitive
Easily controlled
Plasmodium vivax, the ghost parasite
Mostly disappeared in Europe in the mid-20th century,
will reappeared soon…