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INFECTION AND INFECTIOUS PROCESS
DR. N. RAMESH NAIR MATHA HOSPITAL
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SURVIVING SEPSIS CAMPAIGN
GUIDELINES PUBLISHED IN CRITICAL CARE MEDICINE 2013
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INFECTION Infection is a pathologic process caused by invasion of normal sterile tissue, or fluid or body cavity by pathogenic microorganism SEPSIS is systemic response to infection SEVERE SEPSIS is complicated by organ dysfunction SEPTIC SHOCK is a state of acute circulatory failure
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Ineraction between host and microrganism
Predominently pro inflammatory SIRS Mixed antagonistic response MARS Predominently anti inflammatory CARS
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HOST DEFENCE Defense against infection skin and mm
If this is breached immune response falls into INNATE and ADAPTVIE IMMUNE system
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Innate Defense High speed on the the scene reaction to foreign material COMPLIMENT PATHWAYS . Activated compliment produces membrane attack (MAC) which punches holes in the surface of foreign organism PHAGOCYTES Macrophages and Neutrophils NATURAL KILLER CELLS (NK) are in the same family of Lymphocytes
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ADAPTIVE DEFENCE B Lymphocytes producing Ab IgM first Ab very effective in activating compliment and viral neutralizing IgG 75% of Ab in blood IgA most abundant in the body IgE role in defense against parasites T Cells Cytotoxic T Lymphocytes Helper T cell
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Common Pathogens infecting humans
Bacteria Viruses Fungi Parasites Protozoa, helminths
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BODY RESPONSE TO INFECTION
Can be predominently inflammatory SIRS ( Systemic inflammatory response ) Can be predominently anti inflammatory CARS ( Compensatory anti inflammatory syndrome ) Can be mixed MARS ( Mixed antagonistic response syndrome )
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SIRS GENERAL VARIABLES INFLAMMATORY VARIABLES HEMODYNAMIC VARIABLES ORGAN DYSFUNCTION VARIABLES TISSUE PERFUSION VARIABLES
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GENERAL VARIABLES Fever (> 38.30 C)
Hypothermia (core temperature< 36 0 C) Heart rate >90/min Tachypnoea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hr) Hyperglycemia (plasma glucose > 140 mg/dl in the absence of diabetes
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INFLAMMATORY VARIABLES
Leukocytosis (WBC count >12,000/cmm) Leucopenia (WBC count <4000/comm.) Normal WBC count with greater than 10% immature forms. Plasma C-reactive protein more than two so above the normal value. Plasma Procalcitonin more than twice above the normal value.
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HEMODYNAMIC VARIABLES
Arterial hypotension (SBP<90 mm Hg, MAP<70 mmHg, or an SBP decrease>40mm Hg in adults from base line MAP is DBP + 1/3rd PP
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ORGAN DYSFUNCTION VARIABLES
Arterial hypoxemia (Pa00/ Fio0 <300) Acute oliguria (urine output <0.5mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase> 0.5mg/dL Coagulation abnormalities (INR>1.5 or aPTT>60 s) Ileus (absent bowel sounds) Thrombocytopenia (platelet count <100,000 µL -1 ) Hyperbilirubinemia (plasma total bilirubin > 4 mg /dL
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TISSUE PERFUSION VARIABLES
Hyperlactatemia (> 1 mmol/L) Decreased capilary refill
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SEVERE SEPSIS Sepsis – induced hypotension
Lactate above upper limits laboratory normal. Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation. Acute lung injury with Pa00/ Fio0 <250 in the absence of pneumonia as infection source Acute lung injury with Pa00/ Fio0 <200 in the presence of pneumonia as infection source Creatinine >2.0 mg/dL Bilirubin > 2 mg/dL Platelet count <100,000 µL Coagulopathy (international normalized ratio > 1.5)
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Treatment To be completed in 3 hours
Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30ml/ kgm Crystalloid for hypotension or lactate > 4mmol
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Treatment To be completed with in 6 hours
Give vasopressors for hypotension that does not respond to initial fluid resuscitation to maintain MAP > 65mm Hg In the event of persistent hypotension despite volume resuscitation measure CVP and \Central venous oxygen saturation Target CVP > 8mm Hg, Scvo2 >70% and lactate normal
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INITIAL RESUSCITATION
Goals during the first 6 hrs of resuscitation. Central venous pressure 8 – 12 mm Hg. Mean arterial pressure (MAP)> 65 mm Hg Urine output > 0.5 mL/kg/hr Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively . In patients with elevated lactate levels targeting resuscitation to normalize lactate
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Screening for Sepsis and Performance Improvement
Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy Hospital–based performance improvement efforts in severe sepsis
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DIAGNOSIS Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial . At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device. Use of the 1,3 beta-D-glucan assay , mannan and anti-mannan antibody assays , if available and invasive candidiasis is in the differential diagnosis of cause of infection. Imaging studies performed promptly to confirm a potential source of infection (UG).
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ANTIMICROBIAL THERAPY
Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis Antimicrobial regimen should be reassessed daily for potential de escalation Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection
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Combination empirical therapy for neutropenic patients with severe sepsis and for patients with difficult-to-treat, multidrugresistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B).
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INITIAL RESUSCITATION AND INFECTION ISSUES
Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known . Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin . Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause .
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SOURCE CONTROL A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible . When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred . When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) . If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established .
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INFECTION PREVENTION Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; This infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis
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Haemodynamic support and Adjunctive therapy
Fluid Therapy for Severe Sepsis Crystalloids as initial fluid 30 ml/kgm as minimum A portion of this can be albumin More rapid fuid adminisrtion and greater amount needed in some pts
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vasopressors Nor epinephrine as first choice
Dopamine as an alternative only in selected pts with low risk of tachyarrhythmia or absolute bradycardia All pts on vasopressors have an arterial catheter if available INOTROPIC THERAPY Dobutamine infusion up to 20 microgm/kg/mt in presence of myocardial dysfunction or signs of hypo perfusion despite adequate IV volume and adequate MAP
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CORTICOSTEROIDS If adequate fluid and vasopressor cannot achieve haemodynamic stability HYDROCORTISONE 200mg/ day as continous infusion Corticosteroids not given in absence of shock Do not use ACTH stimulation test
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Blood products In the absence of myocardial ischemia or actvie bleeding RBC transfusion only if HB below 7 gm . TARGET 7 to 9 gm Do not use erythropoitin Do not use FFP to correct lab clotting abnormality in the absence of bleeding or planned invasive procedures Platlets prophylaxis if <10000/cm in the absence of bleeding. If pt has risk of bleeding < Higher counts > for active bleeding, surgery, invasive procedure
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Do not use IV IG in adult pts with severe sepsis and septic shock
MECHANICAL VENTILATION for sepsis induced ARDS SEDATION continous or intrmittent sedation be minimized in mechanically ventilated pts. A short course of NMBA of not greater than 48 hrs with early sepsis induced ARDS and PaO2/ FiO2 <150
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GLUCOSE CONTROL Protocol approach when 2 cosecutive readings above 180 mgm Target upper blood glucose < 180 mgm RENAL REPLACEMENT THERAPY for ARF BICARBONATE THERAPY Do not use when hypo perfusion induced lactic acidosis with PH >7.15 DVT PROOHYLAXIS LMWH S/C twice daily. If RF use drug with low renal metabolism. Graduated compression stockings in pts with C/I to heparin
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NUTRITION Oral feeding as tolerated rather than complete IV glucose with in first 48 hrs Low dose feeding up to 500 cals per day and advance only as tolerated Use IV glucose and enteral nutrition rather than TPN STRESS ULCER PROPHYLAXIS PPI
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SETTING GOALS OF CARE Discuss goals of care and prognosis with patients and families
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CAREFUL INFECTION CONTROL PRACTICES
Hand washing Expert nursing care Catheter care Barrier precautions Airway Management Elevation of the head of bed Sub glotic suctioning
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Infections Acquired by HCW from PTS
Viral GE Meningococcal Meningitis Mycobacterium TB Influenza Chickenpox Viral haemorrhagic fever Pertrussis Diphtheria During SARS epidemic of to 60% of HCW got infected with
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Significant Innnoculation of Bloodthrough hollow bore needle
RISKS HB 30% if HBEAg + and 3% if HBEAb + HC 3% if HCV+ HIV 0.3% if donor is HIV +
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Risk Assessment Extent and depth of injury Size and type of needle
Visible contamination of blood Site Source pts HB, HC, and HIV status Stage of illness if HIV + Hepatitis B vaccine status/Ab of recipient Pregnancy
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HCV No immediate intervention HCV RNA tested at 6 and 12 weeks by PCR
Anti HCV tested at 12 and 24 weeks If signs of infection refer to experts for HCV chemotherapy
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HBV HBV status of person exposed
1 dose or less of HBV vaccine- Accelerated course of HBV vaccine at 0, 1 ,2 months . Also give HBIG 2 doses or more- 1 dose of vaccine followed by 2nd dose 1 month later Anti HBS > 10 micromols/ml – one booster dose of vaccine Anti HBS < 10 mmol/ml – HBIg and booster dose of vaccine
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PEP of HCW for accidental exposure to HIV
Needle stick 0.3 %, mucous membrane exposure 0.09% Wash with soap and water, spash water to nose, eyes, mouth, skin Report to authority Blood from pt and HCW send for HIV, HB, HC INITATION OF PEP Do base line HIV ELISA Steat PEP in first 24 hrs preferably with in 2 hrs
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Basic PEP Prophylaxis Zidovudine 300mgm BD + Lamivudine 150 mgm BD A third drug ca be added in case of high risk exposure expanded HIV Post exposure prophylaxis Indinavir 800mgm 8th hrly on empty stomach PEP continued for4 weeks HIV ELISA at 6 weeks, 12 weeks and 6 months Reduces chances of person becoming positive by 80%
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Duration of Antibiotic Therapy for Immunocopetent patients
URINARY TRACT INFECTION Uncomplicated cystitis 3 days Pyelonephritis to 14 days Asymtomatic bacteriuria of pregnancy 3 to 7 days PHARYNGITIS Group A Streptococcus days COMMUNITY ACQUIRED PNEUMONIA CAP 7days HAP 7 to 14 days
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INFECTIOUS DIARRHOEA Cl. Difficile 10 days Salmonella 7 to 14 days Shigella 3 to 5 days Campylobacter 5 days Giardia 10 days SKIN AND SOFT TISSUE INFECTION Impetigo 7 to 10 days Cellulitis 7 to 14 days
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BONE AND JOINT INFECTION
Acute septic arthritis 3 weeks Acute haematogenous osteomyelitis 3 weeks Chronic osteomyelitis weeks INTRAVASCULAR CATHETER INDUCED INFECTION Coagulase negative Staph 5 to 7days S.aureus 14 days Gram negative bacilli 10 t0 14 days Candida days
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MENINGITIS Meningococcal 7 days H. influenza days S. pneumonia to 14 days Group B Streptococcus to 21 days Gram negative bacilli days Listeria > 21 days
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INFECTIVE ENDOCARDITIS
Viridans sstrptococci & S. bovis. (Native) 2 to 4 weeks S,pneumonia & Group A,B,C,E,G streptococci 4 weeks S.aureus ( native valve) 6 weeks S.aureus ( prosthetic valve) > 6 weeks Enterococci ( native or prosthetic ) 4 to 6 weeks HACEK 4 weeks Culture Negative 4 to 6 weeks
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ADULT IMMUNIZATION Disease prevention is the most cost effective option to protect and promote health of populations and immunization is the key to achieve the same Hillman Alan L , Schwartz J , et al American college of Physicians. Annals Internal Med Health 1993; 0003:4819
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Cholera Vaccine ORAL CHOLERA VACCINE Dukoral
Administered as 2 separate doses, 1 to 6 weeks apart for those above 6 years Confers 85% - 90% protection for 6 months among all age groups
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Hepatitis A Virus Havrix® (GlaxoSmithKline) Recommendations:
Universal immunization not recommended as yet Costly vaccine Adults at risk and adults who are negative for anti-HAV antibodies are likely to benefit most
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Vaccination schedule for hepatitis A virus
2 doses 0 and 6 months
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Post-exposure prophylaxis
TWO doses Six months apart In healthy persons [1 and 40 years], a single dose hepatitis A vaccine is preferred to anti-HAV immunoglobulin In persons over 40 years, the manifestations of hepatitis A are more severe Administration of anti-HAV immunoglobulin (0.02 ml/ kg, intramuscularly) as soon as possible, within two weeks following exposure is preferred If the anti-HAV immunoglobulin is not available, the vaccine can be used
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Hepatitis B Virus Administered at 0, 1, and 6 months as an IM injection in the deltoid using a mm needle (Level A) Protection (defined as anti-HBs antibody titer of 10 mIU/ml or higher) following the first, second and third doses of the vaccine has been observed to be 20% to 30%;75% to 80%; and 90% to 95% respectively Recommendations: Indicated for all unvaccinated adults at risk for HBV infection
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Hepatitis B - Post-exposure screening
Required only for patients with ESRD ; CLD ; HIV infection ) sex partners of HBsAg positive person); infants born to HBsAg-positive women , certain health care workers at high risk Performed 1 to 2 months after administration of the last dose of the vaccine series The anti-HBs titre should be maintained above 10 mIU/ml in all groups except in CKD patients on dialysis in whom a titre of over 100 mIU/ml is desired
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Booster doses Not indicated in persons with normal immune status
For CKD patients, assess the need for booster doses by annual anti-HBs antibody titre testing When anti-HBs levels decline to <10 mIU/ ml, annual anti-HBs testing and booster doses should be con sidered for persons with an ongoing risk for exposure (<100 mIU/ml in patients on dialysis)
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Influenza Virus Trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available TIV administered by an annual, single intramuscular dose of 0.5 ml. The LAIV administered by the intranasal use and is approved for use in adults aged up to 50 years
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Influenza vaccine - Recommendations
In the developed countries recommended to people at high risk for influenza-related complications, such as the elderly (age > 65 years); and COPD patients
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Measles, Mumps And Rubella
MMR live attenuated vaccine available as 0.5 ml Administered subcutaneously into the upper arm Recommendations: all adults (except those who have history of suffering from all the three disease / received two doses of MMR For adult immunization, two doses of the vaccine are Recommended
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Meningococcal Meningitis
Recommendations: Routine vaccination of all adults not recommended Can be used during an outbreak; a single dose of bivalent vaccine is recommended days before
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API Guidelines on Pneumococcal Vaccine
Not routinely recommended People with splenectomy API guidelines. Expert group of the Association of Physicians of India on Adult Immunization in India. JAPI. 2009;57:345-55
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Rabies vaccine - Recommendations
Post-exposure treatment: No need to wait for laboratory confirmation of diagnosis to start treatment Immediately post exposure, wound care started, the degree of exposure classified and the post-exposure treatment started The animal observed for 10 days Post-exposure vaccination can be discontinued if the animal is healthy after 10 days 0,3,7,14,28 and 90th days
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Rabies: Passive immunization
Carried out with human rabies immunoglobulin (HRIG) (20 IU/kg body weight; up to a maximum of 1500 IU) or equine rabies immunoglobulin (ERIG) (40 IU/kg body weight; maximum of 3000 IU) ERIG must be given only after administering the test dose Immunoglobulin infiltrated as much as possible into and around the wounds; remaining if any, should be given intramuscularly at a site away from the vaccine site
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Rabies: Management of re-exposure
On re-exposure following a full course of either pre-or postexposure vaccination, 2 booster doses administered intramuscularly or intradermally on days 0 and 3 irrespective of category of exposure or time elapsed since previous vaccination Rabies immunoglobulin is not indicated
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Rabies: Special situations
Rabies vaccines and rabies immunoglobulin are safe during pregnancy, lactation and in immuno-compromised states including HIV infection and AIDS The post-exposure prophylaxis remains the same on exposure to a vaccinated animal
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Typhoid Fever Vaccines available are: (ii) live oral Ty21a vaccine;
(iii) Injectable Vi polysaccharide vaccine; and . Limited data are available on the Vi-rEPA vaccine Live oral Ty21a vaccine is an orally administered live attenuated Ty2 strain of Salmonella typhi
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Typhoid vaccine - Recommendations
Either Ty21a or Vi vaccine may be used as both have comparable efficacy (51% vs 55% at 3 years) and both are safe Between the capsule and liquid formulations of Ty21a, liquid formulation is recommended Three doses of Ty21a capsules/sachets (liquid formulation) administered on alternate days This series should be repeated once in every 3 years as a booster dose.
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Typhoid vaccine - Recommendations
The capsule formulation should be taken orally with plain, cold or lukewarm water Following the administration of the vaccine, food should be taken only after one hour The Vi vaccine is given as a single subcutaneous or intramuscular dose of 0.5 ml. A booster is recommended once in every 3 years
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Varicella Virus Varilrix (GlaxoSmithKline) 2 doses , 2nd dose 4 to 6 weeks after 1st dose Varicella zoster immune globulin (VZIG): Can prevent varicella in nonimmune, healthy individuals if administered within 72 hours of exposure Lowers attack rates among immunocompromized persons if administered no later than 96 hours of exposure Recommended dose is 125 units/10 kg of body weight, up to a maximum of 625 units
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Varicella vaccine - Special situations
Two doses of varicella vaccine are strongly recommended in adults at increased risk for exposure of varicella such as health care personnel etc. Postpartum women who do not have evidence of varicella immunity be given the first dose of vaccine before discharge from the health care facility and second dose 4–8 weeks later Women should be counseled to avoid conception for 1 month after each dose of varicella vaccine All HIV-infected persons with CD4 <200 cells/μL should receive two doses
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Varicella vaccine - Special situations
During outbreaks two-dose vaccination schedule is recommended Post-exposure prophylaxis recommended for unvaccinated persons without other evidence of immunity against varicella; preferably within 3 – 5 days of exposure to varicella rash Contraindications: History of a serious reaction (e.g., anaphylaxis) after a previous dose Women who are pregnant or may become pregnant within 1 month
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Varicella vaccine - Contraindications
Patients with malignant conditions, including blood dyscrasias, leukemia, lymphomas of any type Persons receiving high-dose systemic immuno suppressive therapy including oral corticosteroids HIV-seropositive adult or adolescent with CD4+T-lymphocytes count <200 cells/μL Recommendations for varicella zoster immune globulin: Immunocompromised patients for passive immunization Pregnant women
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THANKS
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