Woman with Cervicitis

Transcription

1 1 Infectious Diseases Update David Spach, MD Last Updated: January 30, 2015 Infectious Diseases 2015 Update STDs Hepatitis C Virus HIV Chikungunya Virus Ebola Virus Sexually Transmitted Diseases

2 2 Woman with Cervicitis A 26-year-old woman presents with a 2-day history of vaginal discharge. She had sex with a new partner 4 days prior. On physical examination, she has a purulent discharge and cervicitis. A Gram s stain of the discharge is shown. What would you recommend for Treatment? A. Ceftriaxone 250 mg IM x 1 + Azithromycin 1g x 1 B. Cefixime 400 mg x 1 + Azithromycin 1g x 1 C. Cefixime 400 mg x 1 + Doxycycline 100 mg bid x 7d D. Levofloxacin 500 mg x 1 + Azithromycin 1g x 1 Gonococcal Isolates and Cefixime Resistance, Source: Bolan GA, et al. N Engl J Med. 2012:366: Updated Gonorrhea Treatment Guidelines Uncomplicated Gonococcal Infection of Cervix, Urethra, or Rectum RECOMMENDED THERAPY Ceftriaxone 250 mg IM x 1 + Azithromycin 1.0 g PO x 1 OR Doxycycline 100 mg PO bid x 7d NOTES: Dose of ceftriaxone now 250 mg (previously 125 mg) Azithromycin preferred over doxycycline because of high rate of tetracycline resistance Cefixime NOT first line anymore Fluoroquinolones NOT recommended Source: CDC and Prevention. MMWR. 2012:61:

3 Updated Gonorrhea Treatment Guidelines Uncomplicated Gonococcal Infection of Cervix, Urethra, or Rectum ALTERNATIVE THERAPY (CEFTRIAXONE NOT AN OPTION) Cefixime 400 mg PO x 1 + Azithromycin 1.0 g PO x 1 OR Doxycycline 100 mg PO bid x 7d Test of Cure in 1 Week NOTES: Alternative regimens for use only when ceftriaxone not available Azithromycin preferred over doxycycline because of high rate of tetracycline resistance Must have test of cure in 1 week Fluoroquinolones NOT recommended, even for alternative Source: CDC and Prevention. MMWR. 2012:61: Rash Syphilis Serologic Screening Traditional Screening Reverse Screening nontreponemal RPR or VDRL EIA or CIA treponemal RPR or VDRL nontreponemal treponemal TP-PA TP-PA treponemal Source: CDC and Prevention. MMWR Recomm Rep. 2011;60(No. 5):133-7.

4 4 Reverse Sequence Syphilis Screening (+) EIA or CIA (-) (+) RPR or VDRL (-) No evidence of syphilis Syphilis (past or present) TP-PA (+) (-) Syphilis (past or present) Syphilis Unlikely Source: CDC and Prevention. MMWR Recomm Rep. 2011;60(No. 5): CDC STD Guidelines Treatment of Syphilis in Adults Stage of Syphilis Preferred Therapy Primary Benzathine penicillin G: 2.4 million units IM x 1 Secondary Benzathine penicillin G: 2.4 million units IM x 1 Early Latent (< 1 year) Benzathine penicillin G: 2.4 million units IM x 1 Late Latent (> 1 year) Benzathine penicillin G: 2.4 million units IM weekly x 3 Tertiary Benzathine penicillin G: 2.4 million units IM weekly x 3 Neurosyphilis Aqueous cystalline penicllin G million units per day, administered as 3 4 million units IV every 4 hours or continuous infusion, for days Source: CDC and Prevention. MMWR Morb Mortal Wkly Rep. 2010:59(RR-12): Hepatitis C Virus

5 5 HCV Treatment A 53-year-old woman with genotype 1 chronic hepatitis C virus infection is seen in the clinic to start HCV treatment. She has F3 fibrosis, but otherwise is in good health. According to AASLD/IDSA guidelines, which one of the following would you recommend for treatment? A. Pegnteferon + Ribavirin x 48 weeks B. Peginteferon + Ribavirin + Sofosbuvir x 24 weeks C. Ledipasvir-sofosbuvir x 12 weeks D. Simeprevir + Sofosbuvir x 6 weeks New Hepatitis C Recommendations AASLD/IDSA/IAS-USA Hepatitis C Guidance: Age-Adjusted Mortality Rates from HBV, HCV, & HIV United States, HIV Rate per 100,000 PY Hepatitis C Hepatitis B Year Source: Ly KN, et al. Ann Intern Med. 2012:156:271-8.

6 Number 6 Hepatitis C: Progression of Disease Normal Liver Chronic Hepatitis Time years years Cirrhosis HCC ESLD Death HCV Infection Forecasted Annual HCV-Related Deaths in the United States Persons with Chronic Hepatitis C and no Cirrhosis in ,000 40,000 Deaths 35,000 30,000 25,000 20,000 15,000 10,000 5, Year Source: Rein DR, et al. Dig Liver Dis. 2011:43: Comparative Treatment Goals with Antiviral Therapy HIV (latent reservoir) HCV (no latent reservoir) HCV RNA Proviral DNA Host DNA Host DNA Host Cell Lifelong suppression of viral replication Host Cell Definitive Viral Clearance Source: KiefferTA, et al. J Antimicrob Chemother. 2010:65:

7 Sustained Virologic Response (%) 7 Therapy for Hepatitis C Projected SVR Rates with Multiple DAAs Timeline IFN 6m IFN 12m IFN + RBV IFN + RBV 6m 12m PEG 12m PEG + RBV 12m PEG + RBV + PI 6-12m Multiple DAAs 3m Direct-Acting Antiviral Agents Simeprevir Ledipasvir-Sofosbuvir Olysio Sofosbuvir Harvoni Ombitasvir-paritaprevir-ritonavir and Dasabuvir Sovaldi Viekira Pak Ledipasvir-Sofosbuvir +/- Ribavirin in Treatment-Naïve HCV GT 1 ION-1 Study: Study Design Week GT-1 Naive n = 214 n = 217 LDV-SOF LDV-SOF + RBV SVR12 SVR12 GT-1 Naive n = 217 n = 217 LDV-SOF LDV-SOF + RBV SVR12 SVR12 Abbreviations: LDV-SOF= ledipasvir-sofosbuvir; RBV = ribavirin Drug Dosing Ledipasvir-sofosbuvir (90/400 mg): fixed dose combination; one pill once daily Ribavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if 75 kg Source: Afdhal N, et al. N Engl J Med. 2014;370:

8 Patients (%) with SVR Patients with SVR 12 (%) 8 Ledipasvir-Sofosbuvir +/- Ribavirin in Treatment-Naïve HCV GT 1 ION-1 Study: Results ION-1: SVR 12* by Treatment Duration and Regimen / / / /217 LDV-SOF LDV-SOF +RBV LDV-SOF LDV-SOF + RBV 12-Week Regimen 24-Week Regimen Abbreviations: LDV-SOF= ledipasvir-sofosbuvir; RBV = ribavirin *Primary end-point by intention-to-treat analysis Source: Afdhal N, et al. N Engl J Med. 2014;370: Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir + Ribavirin in GT1 SAPPHIRE-I Study: Results SAPPHIRE-I: SVR12 in Group A, by Genotype 1 Subtype / / /151 All GT-1a GT-1b Source: Feld JJ, et al. N Engl J Med. 2014;370: AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Therapy for Patients with Genotype 1 Chronic HCV GT 1 HCV: Initial Treatment Genotype 1a Ledipasvir-sofosbuvir x 12 weeks* Ombitasvir-paritaprevir-ritonavir & dasabuvir + Ribavirin x 12 weeks (24 weeks with cirrhosis) Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks (24 weeks with cirrhosis) Genotype 1b Ledipasvir-sofosbuvir x 12 weeks* Ombitasvir-paritaprevir-ritonavir & dasabuvir +/- Ribavirin x 12 weeks (+ ribavirin with cirrhosis) Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks (24 weeks with cirrhosis) *May consider 8-week treatment course in patients with baseline HCV RNA < 6 million IU/ml Source: AASLD/IDSA/IAS-USA ( Viewed April 22, 2014

9 9 Hepatitis C Genotype 1 Costs of Recommended Regimens for Treatment of Genotype 1 Estimated Medication Cost for Treatment of Genotype 1 Chronic HCV Regimen and Duration Regimen Cost Ledipasvir-Sofosbuvir x 8 weeks $63,000 Ledipasvir-Sofosbuvir x 12 weeks $94,500 Ledipasvir-Sofosbuvir x 24 weeks $189,000 Ombitasvir-Paritaprevir-Ritonavir + Dasabuvir +/- Ribavirin x 12 weeks $84,00 Ombitasvir-Paritaprevir-Ritonavir + Dasabuvir +/- Ribavirin x 24 weeks $168,000 Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks $150,000 Sofosbuvir + Simeprevir +/- Ribavirin x 24 weeks $300,000 Source: CDC and Prevention. MMWR. 2012:RR61: CDC Birth Cohort HCV Testing Recommendations In addition to testing adults of all ages at risk for hepatitis C virus: Adults born during 1945 to 1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. Source: Source: CDC and Prevention. MMWR. 2012:RR61:1-32.

10 10 Hepatitis C Testing Methods Screening: Hepatitis C Antibody Testing - Highly sensitive and specific - Reactive test indicates current or resolved infection Y Y Y Supplemental: Nucleic Acid Testing - Quantitative and qualitative HCV RNA tests used - Positive test indicates active infection HIV HIV Screening A 25-year-old gay man is seen in the STD clinic for evaluation of a urethral discharge. He has had 3 new sexual partners in the past 4 weeks. As part of his evaluation and treatment you want to test him for HIV. What does the CDC now recommend for the initial HIV screening laboratory test? A. 3 rd generation HIV EIA an B. Modifed HIV Western immunoblot C. HIV RNA D. 4 th generation HIV antigen-antibody test

11 11 June 27, 2014 Conventional Approach to HIV Diagnostic Testing Initial Enzyme Immunoassay + Supplemental Western blot Source: CDC and Prevention. MMWR Recomm Rep. 2001;50(RR-19):1-57. New Approach to HIV Diagnostic Testing Screening 4 th Generation Antigen-Antibody Immunoassay + Follow-Up HIV-1 & 2 Differentiation Immunoassay

12 CD4 Cell Count Probability of Transmission per Unprotected Coital Act HIV RNA (copies/ml) Antibody Titer 12 Laboratory Diagnosis of Early HIV Infection 10,000,000 1,000, ,000 10,000 1,000 HIV Antibody HIV RNA HIV p24 antigen Days following HIV Acquisition Timing of HIV RNA, HIV p24 antigen, and HIV Antibody Probability of HIV Transmission per Coital Act Over Time th percentile semen HIV-1 RNA load 50 th percentile semen HIV-1 RNA load 25 th percentile semen HIV-1 RNA load Weeks after Infection Source: Pilcher CD et al. J Infect Dis. 2004;189: HHS Guidelines for Initiating Antiretroviral Therapy in Treatment-Naïve Patients 1000 When to Start Antiretroviral Therapy?

13 13 Initial Antiretroviral Therapy Breakfast Lunch Dinner Antiretroviral Therapy: Single Tablet Regimens (STR) Tenofovir-Emtricitabine-Efavirenz Atripla Tenofovir-Emtricitabine-Rilpivirine Complera Tenofovir-Emtricitabine-Elvitegravir-Cobicistat Stribild Abacavir-Lamivudine-Dolutegravir Triumeq Photographs: Andrew Karpenkoand Northwest AIDS Education and Training Center. HIV Treatment as Prevention Antiretroviral Therapy + +

14 CD4 Cell Count 14 HIV Prevention Trials Network (HPTN) Study 052 1,763 HIV Serodiscordant Couples n = 872 n = 853 n = 37 n = 1 13 International Sites (54% of patients from Africa) Source: Cohen M, et al. N Engl J Med. 2011;36: HIV Prevention Trials Network (HPTN) Study Randomization Early Therapy for HIV+ Partner (n=886) CD cells/mm Deferred Therapy for HIV+ Partner (n=877) CD4 < 250 cells/mm 3 or AIDS Related Event Source: Cohen M, et al. N Engl J Med. 2011;36: HIV Prevention Trials Network (HPTN) Study 052 Early Therapy 1 96% Reduction P < Deferred Therapy Linked Transmissions Source: Cohen M, et al. N Engl J Med. 2011;365:

15 HIV RNA < 50 copies/ml 15 Dolutegravir + ABC-3TC versus Efavirenz-TDF-FTC SINGLE Study: Week 48 Virologic Response Abacavir-Lamivudine + Dolutegravir (Triumeq) Tenofovir-Emtricitabine-Efavirenz (Atripla) All 100,000 copies/ml > 100,000 copies/ml Baseline HIV RNA *Note: in actual study participants received separate dosing of dolutegravir and Abacavir-lamivudine pills Source: WalmsleySL, et al. N Engl J Med. 2013;369; Recommended Initial Antiretroviral Therapy Backbone: 2 Medications Anchor: 1 Medication (+/- booster) NRTI Efavirenz NRTI NRTI Tenofovir-Emtricitabine Abacavir-Lamivudine + NRTI II II II Rilpivirine* Raltegravir Elvitegravir + cobicistat Dolutegravir PI Darunavir + ritonavir PI Atazanavir + ritonavir *If baseline HIV RNA < 100,000 copies/ml 2014 HHS Antiretroviral Therapy Guidelines Recommended Initial Antiretroviral Therapy Class Therapy Pill Burden NNRTI-Based Tenofovir-Emtricitabine-Efavirenz Tenofovir-Emtricitabine + Raltegravir INSTI-Based Tenofovir-Emtricitabine-Elvitegravir-Cobicistat Abacavir-Lamivudine-Dolutegravir Tenofovir-Emtricitabine + Dolutegravir PI-Based Tenofovir-Emtricitabine + Atazanavir + Ritonavir Tenofovir-Emtricitabine + Darunavir + Ritonavir Source: 2014 HHS ARV Guidelines. AIDS Info (

16 16 Chikungunya Dengue versus Chikungunya A 46-year-woman presents to clinic 5 weeks after a 4-day trip to Puerto Rico. She recalls multiple mosquitos on the last day of the trip while on a hike. She was asymptomatic during the trip, but 3 days after returning, she developed fever (39-40 C), severe fatigue, and horrible pain in her ankles and wrists. Her fever has resolved but she continues to have very bothersome joint symptoms. Which one of the following most strongly suggests a diagnosis of Chikungunya over a diagnosis of Dengue? A. Region of travel (Puerto Rico) B. Duration of joint symptoms C. Mosquito bites occurring during daytime D. Severity of fever Global Chikungunya (as of January 13, 2015) Source: Centers for Disease Control and Prevention.

17 17 Chikungunya in the Americas (as of January 13, 2015) Source: Centers for Disease Control and Prevention. Chikungunya in the United States (as of January 13, 2015) 11 cases Puerto Rico = 4,168 cases Source: Centers for Disease Control and Prevention. Dengue Source: Simmons CP, et al. N Engl J Med. 2012;366:

18 18 Mosquito Vectors for Chikungunya and Dengue Aedes aegypti Aedes albopictus Predominantly daytime feeders Chikungunya Fever Endemic in parts of Africa and Asia First reports in Western hemisphere in December 2013 Transmitted by mosquitos Incubation 3 to 7days Fever and malaise common Joint pain a major feature of the disease Arthralgias can persist for weeks to months No proven effective treatment Dengue Incubation 3-7 days Phases: febrile, critical, and spontaneous recovery Initial febrile phase characterized by fever, headache, joint pain Initial phase often termed Break-bone fever and lasts 3 to 7 days Minority of patients develop hemorrhagic fever with shock Source: Simmons CP, et al. N Engl J Med. 2012;366:

19 19 Chikungunya Fever Diagnosis Serum and CSF - Antibody testing - Testing performed at CDC Arbovirus Division Tissue - Nucleic acid amplification - Immunohistochemistry - Virus culture Clinical and Laboratory Features of Chikungunya & Dengue Clinical and Laboratory Features Chikungunya Dengue Fever (>102 F or 39 C) Myalgias + ++ Arthralgias +++ +/- Headache Rash ++ + Thrombocytopenia Source: CDC. Chikungunya Virus: Introduction in the Americas. Ebola Virus: Update

20 20 Ebola Virus Ebola Virus Filovirus - Single stranded RNA virus - Filamentous structure Source: Ebola Virus Disease Current Knowledge. N Engl J Med. 2014

21 21 Ebolavirus Source: Feldmann H. N Engl J Med 2014;371: Ebola Virus How do human acquire Ebola virus? Ebola Virus: Transmisssion Source: Ebola Virus Disease Current Knowledge. N Engl J Med

22 22 Ebola Virus: Transmission Source: Ebola Virus Disease Current Knowledge. N Engl J Med Ebola Virus: Early Symptoms Source: International SOS Source: International SOS Ebola Virus: Late Symptoms Source: International SOS

23 23 Epidemic in West Africa through Guinea Liberia Sierra Leone Source: WHO Epidemic in West Africa through Guinea Liberia Sierra Leone Source: WHO. January 30, Epidemic in West Africa through Guinea In late January, fewer than 100 new cases were detected across all three nations. Liberia This is the lowest number of new weekly infections since June Sierra Leone Source: WHO. January 30, 2015.

24 24 Ebola virus: Investigational Treatments Brincidofovir (CMX001) - Oral: Cidofovir prodrug (Phase 2) Zmapp - Injection: combination of 3 human monoclonal AB Favipiravir (T-705, Avigan) - Oral: inhibits RNA-dependent RNA polymerase BCX Oral: inhibits RNA-dependent RNA polymerase TKM-Ebola - Injection: small interfering RNAs Ebola Virus Source: Rampling T, et al. N Engl J Med. 2015;January 28. [Epub ahead of print] Monovalent Chimpanzee Adenovirus Ebola Vaccine ION-1 Trial Design: Phase 1, dose-escalation trial using monovalent Chimpanzee Ebola Vaccine in 240 healthy volunteers to determine safety and immune response Setting: Oxford England (first 60 subjects); Switzerland; Bamako, Mali Entry Criteria: Healthy adults aged Vaccine: - Glycoprotein from Zaire ebola virus, matched to outbreak strain - Adenovirus vector - Single IM administration - 3 dose strengths Primary End-Point: - Safety out to 180 days - Immune Response: IgG and T-cell responses Source: Rampling T, et al. N Engl J Med. 2015;January 28. [Epub ahead of print]

25 25 Ebolavirus Vaccine Antibody Responses to the Zaire ebolavirus Glycoprotein T-Cell Responses to the Zaire ebolavirus Glycoprotein No safety concerns identified at any dose level Source: Rampling T, et al. N Engl J Med. 2015;January 28. [Epub ahead of print] Questions?