Midterms - L4 - Microbial Diseases of the CNS 1-3 PDF

MICROBIOLOGY AND PARASITOLOGY MICROBIAL DISEASES OF THE CNS 1-3 Dr. Hannah Leian Tan So | October 2, 2024 OUTLINE...

MICROBIOLOGY AND PARASITOLOGY MICROBIAL DISEASES OF THE CNS 1-3 Dr. Hannah Leian Tan So | October 2, 2024 OUTLINE Additional information: Introduction A. Brief review of Nervous System Hematogenous/Bloodstream 1. Protective Structures ★the most common route of spread, wherein there is a I 2. CSF more distant initial focus of infection especially in the 3. BBB 4. Infections pulmonary system → pathogens are able to invade the 5. Routes of Infection intravascular space → bloodstream → CNS Microbial Diseases of the CNS ★Respiratory system: most common source of A. Viral agents hematogenous route of infection going into the CNS 1. Poliovirus 2. Rabies Direct Extension B. Fungal agents 1. Cryptococcus neoformans ★Otitis media: the organism that’s causing otitis media C. Bacterial agents spread to the temporal lobe through a direct extension 1. Bacterial meningitis or a contiguous extension of that organism 2. Streptococcus pneumoniae Trauma 3. Neisseria meningitidis II 4. Listeria monocytogenes ★can directly introduce pathogens to the CNS (examples: 5. Haemophilus influenzae bone fracture, medical equipment during procedure) 6. Mycobacterium tuberculosis ★Breach to the integrity of the cranium and meninges, the 7. Neonatal meningitis brain would be vulnerable to the different infectious S. agalactiae agents → result to CNS infection E. coli → example: S. aureus a normal flora of the skin can 8. Bacterial agents C. tetani actually cause CNS infection if there is breach to the C. botulinum integrity of the cranium and meninges → meningitis, M. leprae encephalitis, or meningoencephalitis 9. Specimen Collection Peripheral nerves III APA References IV Freedom Wall ★Rabies and Herpes zoster virus: go up to the CNS via Note: Transcripts were mainly from the discussion while additional important inputs the peripheral nerves (retrograde axonal transport) "emphasized" by doc with clinical correlations also added within text boxes. → Rabies encephalitis is better termed when there is TEG’s note: Kindly refer to the main ppt for the complete tables, diagrams and pictures since they are reduced in size in order to accommodate all of them and for ease of reading. inflammation Check the appendix for the larger versions of important diagrams. I. INTRODUCTION STRUCTURES OF CNS Meninges - the three layers of membranes that enclose the brain and spinal cord → Dura mater - tough outer membrane (“tough mother”) → Arachnoid mater - lacy, weblike middle membrane → Pia mater - firmly attached to brain & spinal cord and has rich blood supply Subarachnoid space → contains many of the blood vessels that feed the brain and spinal cord Figure 1. Sinuses → where CSF flows Source: Dr. Tan’’s ppt → located between arachnoid mater and pia mater II. MENINGITIS ROUTES OF INFECTION Meningitis is inflammation of the meninges, Routes of Infection are divided into 4 main types: including subarachnoid space, leading to a constellation of signs and symptoms and presence Table #1. Routes of Infections of inflammatory cells in CSF Bloodstream or ○ Meningoencephalitis refers to 1 Most common Hematogenous involvement of the meninges, From middle ear (mastoiditis), 2 Direct Extension subarachnoid space, amd brain sinuses parenchyma Bone fractures; neurosurgical Triad of symptoms: 3 Trauma procedures ○ Fever Through Peripheral Rabies virus, Herpes zoster ○ Nuchal rigidity (neck stiffness) 4 Nerves virus ○ Headache Source: Dr. Tan’s ppt other symptoms: altered mental status (>75%), N/V, photalgia, seizures, coma Most common source of infections: LUNGS Transcribed by: secret NMD 2027  Microbial Agents of CNS Infection 1-3 Additional information: TIME DEFINITIONS OF MENINGITIS Triad of symptoms: ★ The most pathognomonic for meningitis ACUTE (80% 1 month to 4 years of age tests (+) LAL in G(-) meningitis Most common cause of acute bacterial meningitis in Source: Dr. Tan’s ppt; Harrison’s Principles of Internal Medicine 20e, p.1000, Table 133-2 adults 3 of 28  Microbial Agents of CNS Infection 1-3 TREATMENT CULTURE CHARACTERISTICS 2-week course of IV meds Enriched media: blood agar plate (BAP), chocolate agar → Penicillin susceptible: Penicillin G plate (CAP) → Penicillin resistant: → Convex, glistening, elevated, mucoid colonies, ▪ 3rd gen cephalosporin (ceftriaxone or cefotaxime) nonhemolytic, opaque or transparent ▪ 4th gen cephalosporin: cefepime ± Vancomycin Selective/enriched media: Thayer-Martin agar (CAP + → + Dexamethasone 10 mg q6 x 4 days antibiotics) ▪ glucocorticoid medication as anti-inflammatory and → Vancomycin - inhibits G(+) to prevent sensorineural deficit (CN VIII) → Nystatin - inhibits fungi → Colistin - inhibits other G(-) Modified Thayer-Martin agar Haemophilus influenzae → Trimethoprim - inhibits Proteus Formerly the most common cause of acute bacterial ▪ Proteus often has swarming colonies and they can meningitis in children 5 months to 5 years of age usually overwhelm other bacteria in the same culture The introduction of immunization against H. influenzae has markedly reduced the incidence of this infection Polysaccharide capsule: → 6 serotypes: a, b, c, d, e, f → Serotype B is the most invasive (Hib) ▪ its capsule is made of polyribitol phosphate ▪ Hib vaccine acts against serotype B GENERAL PROPERTIES Gram(-), nonmotile, encapsulated, coccobacillary Facultatively anaerobic Capnophilic pathogenic bacterium Figure 8. N. meningitidis culture and swarming colonies of Requires X and V factors for growth Proteus → X - hemin Source: Doc Tan’s ppt → V - nicotinamide adenine dinucleotide (NAD) Growth requirements: → Capnophilic - grow best at 5-10% CO2 → Anaerobe or facultative anaerobe → Produce oxidase: a (+) oxidase test is a key test for identifying Neisseria → Catalase (+) Figure 6. H. influenzae Source: Doc Tan’s ppt TREATMENT 7-10-day course of IV meds Figure 9. Oxidase Test 3rd gen cephalosporin (ceftriaxone or cefotaxime) Source: Doc Tan’s ppt Additional information: Neisseria meningitidis ★Oxidase Test → Reagent: Tetramethyl-para-phenylenediamine GENERAL PROPERTIES dihydrochloride (tetramethyl-p-phenylenediamine Gram(-) coffee bean-shaped, nonmotile, encapsulated dihydrochloride) diplococci → When reagent is oxidized: colorless → dark Associated with or found inside polymorphonuclears purple/dark blue compound The serotypes most commonly implicated → (+) Indophenol blue → A, B, C, W135, Y Antigenic structure: → Capsule: provides resistance to phagocytosis and may be important in preventing desiccation → Opa protein: increase bacterial attachment and invasion of host cells; gives the opaque appearance in culture → IgA1 protease: allows colonization of mucosa (cleave IgA found on mucosal surfaces) → Meningococcal LPS endotoxin: ▪ Specific LPS of N. meningitidis is lipooligosaccharide (LOS) Figure 7. N. meningitidis − LPS: Lipid A core and O antigens Source: Doc Tan’s ppt − LOS: shorter because for Neisseria it is limited to 10 units, but still the same toxic effects because lipid A is retained 4 of 28  Microbial Agents of CNS Infection 1-3 ▪ Responsible for the many toxic effects via initiation of of tissue factor → purpura fulminans (blanching the inflammatory cascade – endotoxin, cytokines, petechial rash → large violaceous purpuric rashes → free radicals damage the endothelium “purpura fulminans”) → multiple anticoagulant pathways are downregulated ★Fulminant meningococcemia → hemorrhagic eruption, hypotension, and cardiac depression → rapid enlargement of petechiae and purpuric lesions may be apparent within hours of initial presentation → characteristic PE: rash seen in 50-70% ▪ petechiae relate to the degree of thrombocytopenia, thus the clinician must be vigilant of this rashes as they can be a value in anticipating bleeding complications due to DIC Figure 10. N. meningitidis → Disseminated Intravascular Coagulation (DIC) Source: Doc Tan’s ppt ▪ enhanced thrombosis + decreased fibrinolysis ▪ occlusion of small blood vessels by microthrombi → CLINICAL DISEASE infarction of the skin, adrenal glands, kidneys, brain, Humans are the only natural host and (less common) bones Majority produce asymptomatic colonization (20%), ▪ consumptive coagulopathy (continued carriage in the nasopharynx, especially in adolescents and inflammation and endothelial damage, the platelets young adults and coagulation factors are used up) → increases → Nasopharynx (portal of entry) → bacteremia → bleeding tendency septicemia → Waterhouse-Friderichsen syndrome ▪ adrenal glands fail to function normally secondary to Meningococcemia hemorrhage → sacs of clotted blood as a result of → Early nonspecific symptoms: malaise, weakness, bleeding into the glands myalgias, headache, nausea, vomiting, abdominal ▪ adrenal insufficiency would predominantly seen as pain, and arthralgias are common presenting shock secondary to decreased aldosterone and symptoms cortisol production → Fulminant cases lead to death within hours → Widespread vascular injury characterized by Doc Clarion: endothelial necrosis, intraluminal thrombosis, and ★ Must take note if suspected with meningitis: perivascular hemorrhage → (1) Triad of fever, headache & nuchal rigidity ▪ Initial blanching petechial rash become purpuric ▪ Only applicable in 80% of the cases (purpura fulminans) within hours and often starts on ▪ In few cases: If patient is comatose, no nuchal rigidity is legs and trunk present BOARD EXAM Q: o “Among those patients with bacterial meningitis which one does not present with nuchal rigidity?” Ans: GCS 3 COMATOSE → (2) Identification of causative agent ▪ Per etiology has different treatment regime ▪ Different per age group ★ KERNIG’s sign: → K = knee ★ BRUDZINKSI’s sign → B = batok ★ Bacterial meningitis: (+) Raised intracranial pressure → Perform CRANIAL CT SCAN with contrast to confirm Figure 10. Meningococcemia → If true increased ICP, must medically decompress first Source: Doc Tan’s ppt (lumbar tap) to prevent brain herniation ★ Cryptococcus meningitis Fulminant meningococcemia → Raised/increased opening ICP → Shock → Therapeutic lumbar tap: perform daily to relieve CSF → Disseminated intravascular coagulation: a severe pressure bleeding tendency often simultaneously present with severe thrombosis → Waterhouse-Friderichsen syndrome: bilateral Meningococcal meningitis adrenal hemorrhage that may lead to adrenal necrosis → most important complication + purpura fulminans + sepsis → acutely inflamed meninges → sudden onset of severe headache, vomiting and stiff Additional information: neck; can progress to coma within a few hours ★Meningococcemia - a meningococcal septicemia → commonly associated with altered mental status → early symptoms are nonspecific and suggest a viral (confusion), drowsiness or lethargy illness → fulminant cases lead to death within hours of initial symptoms ★Endothelial injury is central to many features of meningococcal septicemia → epithelial injury → increased vascular permeability → hypovolemia, tissue edema, and proteinuria → there is subsequent loss of thromboresistance and Figure 25. Pathogenesis of DIC in Sepsis increased perivascular coagulation from upregulation Source: Doc Clarion’s ppt 5 of 28  Microbial Agents of CNS Infection 1-3 LABORATORY DIAGNOSIS Clinical Specimens → Blood culture, CSF, nasopharyngeal swab, puncture material from hemorrhagic lesions → Gram stain or culture Culture: ★ Modified Thayer Martin: ▪ Convex, glistening, elevated, mucoid colonies, 1-5mm diameter, opaque or transparent ▪ Selective medium due to antibiotics used: o Vancomycin, Colistin & Nystatin: = Inhibits contaminants including non pathogenic Neisseria Source: Doc Tan’s PPT Doc Clarion: ★ Case: An adult living in a dormitory presented with headache and nuchal rigidity → Dx: Neisseria meningitidis ★ Latest candle jar culture: Gaspak jar ★ MTM - selective BAP medium Figure 26. Laboratory process and findings → Vancomycin: inhibit gram positive Source: Doc Clarion’s ppt → Colistin: inhibit gram negative → Nystatin: anti-fungal structures ★ Biochemical: Growth requirements → N. meningitidis: ferments glucose + maltose only → Fastidious organism, oxidase positive → Ferments glucose and maltose Doc Clarion: → Grow best in an atmosphere containing 5% CO2 (candle jar culture) ★ Case: A child presented with fever, headaches, & decreased sensorium. Brought to the ER via taxi, door opened by the Serology guard, vital signs taken by a nurse. The patient had a seizure. → Latex agglutination or hemagglutination tests Upon checking by the attending physician, he suspected ▪ For detection of meningococcal capsular meningococcemia. Who shall receive a post-exposure polysaccharide / meningococcal antigens or prophylaxis? antibodies → Ans. All who had direct contact with the patient ★ Post-exposure prophylaxis: CEFTRIAXONE ★ For carrier state: → Rifampicin → Ciprofloxacin TREATMENT, MANAGEMENT AND PREVENTION Treatment ○ Penicillin G - drug of choice ○ Chloramphenicol or 3rd generation cephalosporin (cefotaxime and ceftriaxone) for those with allergy to penicillins Management of close contacts, eradication of carrier state: ○ Rifampin 600 mg PO q12 x 2 days ○ Azithromycin 500 mg PO single dose ○ Ceftriaxone 250 mg IM single dose Prevention: ○ Meningococcal vaccine (containing serogroups A, C, Y, and W-135) given in Source: Doc Tan’s PPT persons between 9 months to 55 years old ○ 0, 1-2, 6 months schedule SUMMARY: ○ Recommended especially for high risk groups: Antigens specific for the antibody of interest coating Persons with functional of insoluble particle such as polystyrene → Patient Serum surgical asplenia could contain the antibodies of interest → Agglutination Persons with C’ deficiencies (where the antibodies or antigens interconnect via Travelers to highly endemic areas bridges to the antigen or antibody particles) “Closed populations” (dormitories, Antibodies specific for the antigen of interest coating military, children in daycare) insoluble particle such as polystyrene → Patient Serum Clinical laboratory workers could contain the antigen of interest → Agglutination (where the antibodies or antigens interconnect via Doc Tan: bridges to the antigen or antibody particles) Vaccination for high risk groups: 3 doses of primary series Biochemical Tests ○ 1st dose: NOW ○ Catalase (+) ○ 2nd dose: 1-2 months after the 1st dose ○ Oxidase (+) ○ 3rd dose: 6 months from the 1st dose ○ Glucose and maltose fermentation 6 of 28  Microbial Agents of CNS Infection 1-3 Streptococcus agalactiae (Group B Streptococci) Gram-positive cocci in chains Primary (1st) common cause of meningitis among newborns Clinical disease in neonates and infants Streptococcal information Source: Dr. Clarion’s ppt TREATMENT AND PREVENTION 25% of mothers are vaginal carriers: Prevention: Intrapartum antibiotic prophylaxis Screening of pregnant women at 35-37 weeks of ○ Screen pregnant women at 35-37 weeks pregnancy age of gestation (culture of rectal and/ or Biochemical: vaginal swabs) → Gram-positive cocci in chains Intrapartum prophylaxis → Beta-hemolytic ○ Penicillin G: 5M U IV loading dose → Encapsulated followed by 3M U IV q4 [FIRST LINE → CAMP test (+) DRUG] → Hydrolyzes sodium hippurate (+) Virulence factors ○ Ampicillin: 2 g IV loading dose followed ○ Pili by 1g IV q4 for attachment to epithelial cells and Treatment stabilized colonization ○ Penicillin G ○ Granadaene ○ Ampicillin + gentamicin orange- red pigment that acts as ○ Cefotaxime hemolysin effectively resists the elimination by mast cells, macrophages, and neutrophils Listeria Monocytogenes aids in colonization ○ Capsule for effective biofilm formation GENERAL PROPERTIES defends from deposition of complement, Short, gram positive opsonization and phagocytosis Non-spore forming bacilli ○ Beta-hemolysin Facultative anaerobe ○ CAMP factor Beta-hemolytic rods pore-forming protein that enhances Biochemical: hemolysis → Catalase (+) Only enhances hemolysis; NOT AN → Esculin hydrolysis (+) ACTUAL HEMOLYSIN → Acid former, non-gas former (H2S -) + CAMP: Streptococcus agalactiae Survive: → Refrigerator temperature (4 degrees Celsius)) [UNIQUE CHARACTERISTIC] → Under low pH → High salt conditions ★ Liquid medium: Tumbling-end motility → Seen only at 22 - 28 C (peritrichous flagella) but not at 37 C / body temperature (peritrichous is lost) ★ Solid medium: Umbrella motility BAP medium: → Beta hemolytic (complete hemolysis) Source: Doc Tan’s PPT PATHOGENESIS: Can produce cytolysin: → cause damage to the lung tissue which enables them to gain access to the bloodstream and reach the CNS → used also in invading the meninges and nervous tissue leading to tissue destruction MOT: → in utero → vaginal delivery Gram stain, Liquid & Solid medium & Vaginal colonization GBS during pregnancy: Beta-hemolysis of L. monocytogenes → increases the risk of vertical transmission and Source: Doc Clarion’s ppt early-onset disease in neonates. 7 of 28  Microbial Agents of CNS Infection 1-3 Adults → Immunocompetent non-pregnant adults ▪ Mild, self-limiting gastroenteritis lasting 1-3 days ▪ Foods commonly implicated in the disease: − Pre-prepared fruit or vegetable salads − Ready to eat packaged and unpackaged cold deli meats − Rockmelon − Cold cooked chicken Source: Doc Tan’s PPT * − Soft serve ice cream Culture and growth characteristics: − Pate or meat spreads ○ Grows on media with 5% sheep blood agar − Soft cheeses and unpasteurized dairy products showing small zone of hemolysis around − Chilled, raw and smoked seafood and pre-cooked and under the colonies prawns ○ Catalase (+) → Immunocompromised patients ○ Oxidase (+) ▪ Develop Listeria meningoencephalitis and ○ 13 known serovars based on O (somatic) bacteremia and H (flagellar antigens Antigenic structure: ▪ Meningoencephalitis and focal CNS infection ○ Internalins A and B − Most common in immunocompromised patients Interact with E-cadherin − Invasion of the brain parenchyma produces either (receptor) to facilitate cerebritis or focal abscess phagocytosis in cells that are not − Blood cultures often (+) normally phagocytic − CSF findings minimally abnormal ○ Listeriolysin O (LLO) ▪ Meningitis Specific beta-hemolysin − presentation is more frequently subacute (will Mediates rupture of the illness developing over several days); nuchal phagosomal membrane rigidity and meningeal signs are less common ○ PLC A and PLC B Dangerous for pregnant women Allows escape of bacterium into cytoplasm along with listeriolysin → Due to its ability to cross the placenta and cause O infection in the fetus ○ ActA → Result: Premature birth, spontaneous abortions, or Mediates the nucleation of host stillbirth. actin filaments to propel the bacteria intra-and intracellularly → Nonspecific acute or subacute febrile illness with myalgia, arthralgia, backache, headache PATHOGENESIS: → Usually bacteremic Infections with L. monocytogenes follow ingestion of contaminated food → Involvement of the CNS is uncommon, but preterm L. monocytogenes induces its own internalization by delivery is a common complication cells that are not normally phagocytic (by releasing Internalin) 2 forms of perinatal human listeriosis (Infection in ○ Internalin-mediated entry is important in Neonates) the crossing of intestinal, blood-brain, and fetoplacental barriers EARLY ONSET SYNDROME (granulomatosis ○ Prominent infection with decreased infantiseptica) cell-mediated immunity ○ Iinfection in utero and is disseminated characterized by Doc Clarion: Neonatal sepsis ★ Case: A diabetic patient ingested a contaminated food found in Pustular lesions their refrigerator. Granulomas containing ▪ Organism infiltrates intestine using its internalin → can L. monocytogenes in multiple traverse the cardiovascular system organs Internalin: mediates bacterial adhesion and invasion of epithelial cells in the human intestine through specific interaction with its host cell receptor E-cadherin (ncbi). ★ More detrimental if pregnant esp to baby: ▪ Can lead to chorioamnionitis, premature birth or worse, abortion ★ Pseudopods ▪ Since facultative anaerobes, they traverse to the basement membrane to crawl into neighboring cells. ▪ Cannot be identified by sentinel cells if already inside the cell. CLINICAL PRESENTATION In most healthy individuals → Infection will result in no symptoms or only mild flu-like symptoms Others: symptoms including headache, fever, myalgias, abdominal cramps, vomiting and diarrhea. Source: Doc Tan’s PPT 8 of 28  Microbial Agents of CNS Infection 1-3 LATE ONSET SYNDROME Source: Doc Tan’s PPT Typical meningitis PATHOGENESIS: Causes meningitis between birth and the M. tuberculosis enters the host by droplet 3rd week of life with significant mortality inhalation, and initially infect alveolar macrophages rate Localized infection worsens in the lungs, and then Mothers are not usually ill / no history disseminates to the regional lymph nodes of illness A significant bacteremia begins that can seen bacilli to other organs, including CNS In the brain, MTB may form foci of metastatic caseous lesions Tubercles rupturing into the subarachnoid space cause meningitis, whereas those deeper in the parenchyma cause tuberculomas or abscess. Placental findings CLINICAL PRESENTATION: Source: Doc Clarion’s ppt Starts as pulmonary tuberculosis with characteristic radiologic findings: DIAGNOSIS ○ Ghon (primary) focus / lesion Isolation of the organism from cultures of blood, subpleural tuberculous caseating CSF, or amniotic fluid granuloma (tuberculoma) CT or MRI for parenchymal involvement first and earliest CSF studies minimally abnormal ○ Ghon complex Ghon focus + ipsilateral TREATMENT mediastinal lymphadenopathy Meningitis, neonatal infection ○ Ranke complex ○ 3 week course of IV ampicillin 2g IV q6 + Ghon complex that has healed gentamicin and calcified D ○ 2 week course for bacteremia in pregnant Penicillin - allergic ○ Trimethoprim-sulfamethoxazole 15-20 mg/kg/day IV q Mycobacterium Tuberculosis GENERAL PROPERTIES: Gram-staining neutral, rod-shaped, non-spore-forming, thin aerobic bacterium ○ Acid fastness due mainly to the high content of mycolic acids Ghon (primary) focus/ lesion Extensive linking of cell wall lipids - low intracellular Source: Doc Tan’s PPT permeability of antibiotics Lipoarabinomannan Tuberculous Cranial Meningitis (TBM) ○ involved in the pathogen-host interaction ○ 2-3 week long prodrome of fever, and facilitates the survival of M. headache, malaise, weight loss, tuberculosis within macrophages drowsiness, confusion ○ Basal meningitis: ocular paresis (common) ○ Obstructive hydrocephalus from obstruction of basilar cisterns Source: Doc Tan’s PPT Growth and culture characteristics: M. tuberculosis divides every 18-24 hours, incubated at least 4 weeks Catalase (+) Liquid media: Middlebrook 7H9 or 7H12 Source: Doc Tan’s PPT Solid-egg based media: Lowenstein-Jensen agar ○ Brown, granular colonies Tuberculous Spinal Meningitis Solid agar-based media: Middlebrook 7H11 or ○ May manifest as an acute, subacute, or 7H10 chronic form ○ The clinical picture in primary spinal meningitis is often characterized by progressive ascending paralysis, eventually resulting in basilar (cranial meningitis) Muscle weakness starts to the legs and spreads to the arms → Basilar (Cranial Meningitis) 9 of 28  Microbial Agents of CNS Infection 1-3 Tuberculomas ○ Well-circumscribed intraparenchymal NON-POLIO ENTEROVIRUSES masses of granulomatous caseous >85% of viral meningitis cases necrosis often associated with meningitis Picornaviridae ○ May cause mass effect if LARGE ○ Include echoviruses, coxsackieviruses A and B, polioviruses, and the numbered enteroviruses ○ Icosahedral, nonenveloped, linear, single-stranded RNA viruses ○ Coxsackievirus most common cause of aseptic meningitis Epidemiology: ○ Immunocompromised and children 0.1 ng/mL An alternative is penicillin, although this drug in some PCR of Toxin studies has been shown to exacerbate spasms → In one study, was associated with increased mortality Treatment Antitoxin should be given early in an attempt to deactivate any circulating tetanus toxin and prevent its Immunotherapy with tetanus antitoxin (3000-6000 U uptake into the nervous system IM) → Two available preparations: human tetanus Surgical debridement - the entry wound should be immunoglobulin and equine antitoxin identified, cleaned, and debrided to remove anaerobic foci of infection and prevent further toxin production Prevention Active immunization with toxoid (TTCV): 3 primary doses Metronidazole - 400 mg rectally or 500 mg IV q6 x in infancy + booster doses 7 days → Primary series: at 6, 10, 14 weeks old ○ preferred antibiotic → Booster 1: at 12-23 months → Booster 2: at 4-7 years old Additional information: → Booster 3: at 9-15 years old Dr. Tan’s Lecture: Diagnosis is based on history and clinical presentation Additional information: The WHO definition of adult tetanus requires at least Dr. Tan’s Lecture: one of the following signs: To be protected throughout life, WHO recommends that → trismus (inability to open the mouth due to rigid an individual receives 6 doses (3 primary doses plus 3 contraction of the jaw muscle) booster doses) of tetanus toxoid-containing vaccines → risus sardonicus (sustained spasm of the facial → The 3-dose primary series should be given as early as muscles) 6 weeks of age with subsequent doses given with a → painful muscular contractions (requires history of minimum interval of 4 weeks in between injury or wound) → The 3 booster doses should preferably be given during → tetanus may also occur in patients who do not the 2nd year of life, at 4-7 years of age, and lastly at remember a specific wound or injury 9-15 years of age Ideally, there should be at least 4 years between booster doses Adjunctive Tests Wound culture on BAP, Gram Staining Proper care of wounds contaminated with soil Serology- protective IgG level at 0.1 ng/mL Use of safe, clean delivery and cord-care practices PCR of toxin Prophylactic use of antitoxin Additional information: → (tetanus immunoglobulin, TIg) Dr. Tan’s Lecture: Previous Clean Wounds Dirty Wounds No confirmatory lab tests but adjunctive studies can help confirm the diagnosis TTCV TTCV TIg TTCV TIg Specimen is ideally excised tissue from necrotic depths of Doses the wound 50% blood glucose; 15-45 mg/dL 50-180 mm lymphocytes 45-85 mg/dL H2O Purulent >1000, 80% 100 ↑↑↑↑ Gram stain (Bacterial) PMNs 300 CSF culture decrease LAL test Aseptic 100-1000 Normal Normal to Mod. N° to ↑ PCR (Viral) lymphocytes high; >50 mg/dL 150-300 Tuberculous 25-100;