Meningococcal Disease PDF

LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria MENINGOCOCCAL DISEASE GLOBAL NUMBER OF MENINGITIS DEATH BY ETIOLOGY & AGE (1990 & 2019) • • • • • • Global statistics comparing 1990 & 2019 – not updated Shows common isolates way back 1990 to the most recent that has glob...

LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria MENINGOCOCCAL DISEASE GLOBAL NUMBER OF MENINGITIS DEATH BY ETIOLOGY & AGE (1990 & 2019) • • • • • • Global statistics comparing 1990 & 2019 – not updated Shows common isolates way back 1990 to the most recent that has global statistics When talking about meningitis in general the common organisms or pathogens would be different depending on what age group: o Adults § Streptococcus pneumoniae – 1st / most common § Neisseria meningitidis – 2nd cause § Haemophilus influenzae § Listeria monocytogenes o Neonates § Strep agalactiae – normal flora in the vagina of pregnant women In 1990, N. meningitidis is the most common because during those times there has been some outbreaks especially in the meningitic belt, which is in Africa In 2019, most common is Strep pneumonia, in all age groups and close is N. meningitidis and Klebsiella Pneumoniae The huge difference is that the significant decrease in H. influenzae because of the availability of vaccines (HiB vaccine) WHO 2019 report • No reliable estimates of global meningococcal disease burden due to inadequate surveillance • Meningococcal meningitis is associated with high fatality (up to 50% when untreated) • Largest burden in sub-Saharan Africa known as the meningitic belt • When talking about global estimates, there’s a difficulty because of inadequate surveillance o A lot of these patients with meningitis, don’t undergo diagnostics to be able to identify the main causative agent o Before staring antibiotics especially on the 1st hour, do lumbar puncture before starting antibiotic o In some cases, it’s a matter of urgency / emergency to start antibiotics Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the global meningococcal initiative • • • • • • • • 💜🥕 Shows total number of cases Has gone done tremendously for Influenza The most common cause of meningitis would still be VIRAL because it’s common in children and most commonly occur in children Data in the Philippines only reflects the septicemic form or meningococcemia Some patients with meningococcemia may not present as meningitis When talking about meningococcemia, it’s talking about Neisseria Meningitidis in the circulation or bacteremia due to meningitidis It’s easier to do a diagnosis of meningococcemia because of some of S & Sx Difficult to give definitive dx of meningitis due to N meningitidis because of presentation of meningitis in all patients is quiet the same o Presentation for Adults: Fever, Headache, Nuchal rigidity and it’s Impossible to differentiate one from another o Unless patient presents with purpuric lesions 1 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria Invasive meningococcal disease in Malaysia, Philippines Thailand, and Vietnam: An Asia-Pacific expert group perspective on current epidemiology and vaccination policies; 9 Sep 2022 Incidence data • Meningococcal disease is endemic to Philippines, with about 100 cases reported yearly and no seasonal variation. • 130 meningococcal cases from January 1 to 29 June 2019 • 49.2% (64/130) aged <5 years, and 25.4% (33/130) aged <1 year • Overall Case Fatality Rate (CFR) of 50% • Annual incidence of 0.02 cases per 100,000 population study on carriage among school and university students (age 5-44 years): • MenB was the predominant serogroup (65.7%), followed by MenC (8.6%), and MenY (5.7%) • • • Invasive disease are usually encapsulated, and the antigenic nature of the capsule determines an organism’s serogroup 13 serogroups: A-D, 29E, W-Z, H-J, and L, but just 6 serogroups account for the majority of cases of invasive disease. Most important in this serogroup would be 6 serogroups (A,B,C,W,X,Y) SAN LAZARO HOSPITAL 2016-2018 (N=27 isolates) Meningococcemia Cases & Deaths (San Lazaro Hospital, 20142018) Year 2014 2015 2016 2017 2018 (Jan – Jun) Pediatrics Cases Deaths 20 14 16 5 20 7 23 8 12 4 Cases 2 1 3 5 4 Adult Deaths 1 1 3 3 Cases 22 17 23 28 1 16 Total Deaths 15 6 10 11 5 • • Majority are from NmB, NmE, NmW MOST COMMON IS NmB CAUSATIVE AGENT NEISERRIA MENINGITIDIS • Fastidious, gram-negative aerobic diplococcus • Catalase- and oxidase-positive organism that utilizes glucose and maltose to produce acid • • • N. meningitidis o Both GLUCOSE & MALTOSE N. gonorrhea o Acid producing from GLUCOSE N. Lactamica o Glucose Maltose Lactose ETIOLOGY Global data • Black - more common serogroups • White – minor serogroups causing meningitis 💜🥕 2 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria • • • Green – Streptococcus Pneumionae; most common globally Yellow – H. Influenza B STRUCTURE POLYSACCHARIDE CAPSULE Important in pathogenesis Serves as a barrier by inhibiting host phagocytosis & complement-mediated lysis Remember: N. meningitidis is gram-negative and when talking about gram-negative a lot of the pathogenesis is due to endotoxin production in gram-negative organisms is the lipopolysaccharide However, for both N. meningitidis and N. gonorrhea, instead of calling it LPS, it’s called LOS (lipoligosaccharide) because there’s less of that antigenic repeats of saccharides in that strand of lioligosaccharide o o • • Pilus or Pili together with the OPA PROTEINS, they actually responsible for ADHESION PorB – responsible for the classification of N, meningtidis, able to divide into groups using PorB and into some groups using PorA PATHOGENESIS • N. meningitidis is an effective colonizer of the human nasopharynx • Mode of transmission: INHALATION • High rates of carriage among adolescents and young adults o There may be patients with N. meningitidis in the oropharynx, without presenting any S & Sx ( CALLED CARRIERS) • Many of the same factors that increase the risk of meningococcal disease also increase the risk of carriage: o Smoking o Crowding o Respiratory viral infection • A lot of these invasive infections due to N. meningitidis would start as viral infection before it develops meningococcemia • • • • • Colonization of the nasopharynx involves a series of interactions of meningococcal adhesins (Opa proteins & Pili) with other glands on the epithelial mucosa o Colonization starts from with ADHESION o Opa protein and pili would adhere to some epithelial mucosa with certain adhesions receptors Since transmission is through inhalation, and this organism if it’s in the respiratory mucosa, there’s certain defense there IgA (immunoglobulin A) would check the adhesion of certain pathogens N. meningitidis produces an IgA1 protease that is likely to reduce interruption of colonization by mucosal IgA. o That’s why some of these organisms from being a colonizer, becomes a TRUE PATHOGEN The meningococcal capsule is an important virulence factor: provides resistance to phagocytosis and may be important in preventing desiccation o If they’re in the tissues, aside from the immunoglobulins that would be attacking the organism, PHAGOCYTIC CELLS would do their role however because of the CAPSULE this would prevent phagocytosis and prevent desiccation transmission between hosts Photo of N. meningitidis cell wall 💜🥕 3 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria o If those droplets, land on certain surfaces the bacteria will not die easily because of the capsule • 1. 2. 3. 4. • Starts as colonization in the respiratory mucosa Invasion of the epithelium through endocytosis and would go the epithelial and endothelial cells Invasion of blood and go to the circulation Further dissemination N. meningitidis has TROPHISM to the CNS that’s why a lot of the infections patients may not have meningococcemia (meaning body is strong enough to prevent bacteremia or meningococcemia from happening) However, the defense is not enough so it will be eaily enter the blood brain barrier WHAT HAPPENS IF NEISSERIA MENINGITIDIS ENTERS THE BODY • Once the organism is in the bloodstream, its growth may be limited if the individual is partially immune, although bacteremia may allow seeding to other sites, such as the meninges or the joints. • During growth, meningococci release blebs of outer membrane containing outer-membrane proteins and LOS. o LOS is found in the surface of the organism and during growth there would be some blebs on the surface of the organism and this would contain outer membrane proteins together with LOS, and LOS will be the one that would be releasing the endotoxin • Endotoxin binds cell bound CD14 in association with TLR4 to initiate an inflammatory cascade with the release of high levels of various mediators, including TNF α, IL 1, IL-1β, IL-6, IL-8, IL-10, plasminogen activator inhibitor 1 (PAI-1), and leukemia inhibitory factor. o The endotoxin will bind to the receptors and if it’s in the circulation it would bind to the monocyte, and if it’s in the tissue it would bind to the macrophages and receptors are used like CD14 toll-like receptor 4 o Like in HIV there’s receptor and co-receptor • Soluble CD14-bound endotoxin acts as a mediator of endothelial activation. 💜🥕 • • • • • Endotoxin will bind to LOS binding proteins and they would attach to the CD14 of monocytes or macrophages and TLR4 What would happen to these monocyte and macrophage? It would increase synthesis of tissue factor, dysregulation of coagulation and release of proinflammatory cytokines like (TNFa & IL1) leading to organ dysfunction There are those don’t bind to the cells called SOLUBLE o Endotoxin with LOS binding protein and CD14 may not be adherent to the cells, but they would just be in the circulation and this is the on that would adhere to the endothelium One of the defense is NEUTROPHIL ACTIVATION o Endotoxin with the help of an antibody would adhere to neutrophils and this would lead to release of proteolytic enzymes (proteases) leading to endothelial injury o Proteases and soluble CD14 join forces to cause ENDOTHELIAL INJURY o Majority of the complications that encountered in invasive meningococcal disease is due to ENDOTHELIAL INJURY o Central to the pathogenesis of invasive meningococcal disease is the SOLUBLE CD14 leading to CAPILLARY LEAK, INTRAVASCULAR THROMBOSIS, CARDIAC DYSFUNCTION & MULTI-ORGAN FAILURE 4 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria • • • • manifesting as darkening on the fingers and nail beds and cyanosis on the fingers. Infarction in the limbs called PURPURA FULIMANS Anticoagulant pathways are downregulated through loss of endothelial thrombomodulin and protein C receptors and decreases in levels of antithrombin III, protein C, protein S, and tissue factor pathway inhibitor. Thrombolysis is also profoundly impaired in meningococcal sepsis through the release of high levels of PAI-1. As a consequence of the Endothelial injury → increased vascular permeability attributed to loss of glycosaminoglycans and endothelial proteins → gross proteinuria. “CAPILLARY LEAK SYNDROME” → leads to hypovolemia, tissue edema, and pulmonary edema (THIRD SPACING) Initial compensation → vasoconstriction and tachycardia → cardiac output eventually falls • • • • • • • As a consequence of the Endothelial injury there will be INCREASED VASCULAR PERMEABILITY In the urine there will be gross proteinuria In the tissue, because of the capillary leak causing HYPOVOLEMIA and patients will experience HYPOVOLEMIC SHOCK (3rd spacing – tissue edema & pulmonary edema) When the volume of fluid is decreasing, the blood vessels would try to compensate through VASOCONSTRICTION and TACHYCARDIA and because of this there will be decrease CARDIAC OUTPUT leading to SHOCK • • • Shock in meningococcal septicemia attributable to: o Hypovolemia, which results from the capillary leak syndrome secondary to endothelial injury o Myocardial depression, which is driven by hypovolemia, hypoxia, metabolic derangements (e.g., hypocalcemia), and cytokines (e.g., IL-6). Decreased perfusion of tissues is a result of: o Intravascular thrombosis o Vasoconstriction o Tissue edema o Reduced cardiac output Widespread organ dysfunction Later in the disease—a decreased level of consciousness due to CNS involvement WHAT HAPPENS IN THE PATIENT • • • • 💜🥕 Intravascular thrombosis occurs in some patients with meningococcal disease and results in purpura fulminans and infarction of areas of skin or even of whole limbs. When there is problem in the coagulation, patient will have thrombosis But before the actual thrombosis, there will be patients presenting with petechiae and you would think of it as dengue or other viral infection However, petechiae of these patients would rapidly evolved into purpuric lesions (ecchymosis) and specially if the thrombosis involves the distal blood vessels, it would primarily affect the distal extremities • • Bacteria → reach the meninges → local inflammatory response release of a spectrum of cytokines → neuronal injury. Local endothelial injury → cerebral edema and raised intracranial pressure. CLINICAL MANIFESTATIONS • INCUBATION PERIOD: 1-10 days (usually < 4 days) 5 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria • • • At the onset, patients can present with fever and signs of an upper respiratory tract infection without toxicity. Myalgia may be intense and the presentation may be mistaken for influenza. Median time from onset of symptoms to hospital admission was estimated at less than 22 hours in 1 study. • Some patients (including those with overwhelming sepsis) may have no rash (< than 10% of children) o If checking for the VS there will be decrease BP and patient becomes tachycardic = SEPSIS MENINGITIS • Fever, vomiting, and (especially in infants and young children) irritability • Indistinguishable from other forms of bacterial meningitis unless there is an associated petechial or purpuric rash, which occurs in two-thirds of cases. • Headache (very severe) is rarely reported in early childhood but is more common in later childhood and adulthood. o FOR ADULTS CHECK FOR TRIAD: FEVER, HEADACHE, NUCHAL RIGIDITY • Neck stiffness, photophobia, decreased level of consciousness, seizures or status epilepticus, and focal neurologic signs • 30–50% of patients present with a meningitis syndrome alone (Meningitis with meningococcemia) • Most deaths from meningococcal meningitis alone (i.e., without septicemia) are associated with raised intracranial pressure presenting as a reduced level of consciousness, relative bradycardia and hypertension, focal neurologic signs, abnormal posturing, and signs of brainstem involvement—e.g., unequal, dilated, or poorly reactive pupils; abnormal eye movement; and impaired corneal responses CUSHING REFLEX - REFLEX IN PATIENTS WITH MENINGITIS HAVING HYPERTENSION OR RELATIVE BRADYCARDIA • A physiological nervous system response to acute elevation of ICP, resulting to CUSHING’S TRIAD OF: o Widened pulse pressure (increasing systolic, decreasing diastolic), bradycardia, and irregular resprations - PUBMED Most common clinical syndromes are meningitis and meningococcal septicemia • May also present as pneumonia, pyogenic arthritis or osteomyelitis, pericarditis, endophthalmitis, conjunctivitis, primary peritonitis, or (rarely) urethritis • Pneumonia is not commonly reported but is associated with serogroups Y, W, and Z and appears most often to affect individuals >10 years of age RASH • • • • 💜🥕 often absent early in the illness Initially blanching in nature (macules, maculopapules, or urticarial), indistinguishable from more common viral rashes Becomes nonblanching rash (petechial or purpuric) o Use glass or transparent tumbler to check the rash and wear gloves and clean properly the glass and tumbler because sometimes organisms can be found in the lesions In the most severe cases, large purpuric lesions develop (purpura fulminans) SEPTICEMIA • Septicemia alone accounts for up to 20% of cases of meningococcal disease • Condition may progress from early nonspecific (influenzalike) symptoms to death within hours. o PROGRESSION IS VERY RAPID • Rash, if present, may appear to be viral early in the course until petechiae or purpuric lesions develop • Purpura fulminans occurs in severe cases, with multiple large purpuric lesions and signs of peripheral ischemia. 6 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria • • • Limb pain, pallor (including a mottled appearance and cyanosis), and cold hands and feet may be prominent Decreased cerebral perfusion leads to confusion, agitation, or decreased level of consciousness. With progressive shock, multiorgan failure ensues; hypotension is a late sign in children, who more commonly present with compensated shock (tachycardia, poor peripheral perfusion, and normal blood pressure) Septicemia is not equivalent to sepsis. (Not used anymore in new guidelines) – It’s the same as bacteremia Once patient is having confusion, decreased level of consciousness that’s already SEPSIS If patient presents with LOW BP and not responsive to fluid management = SEPTIC SHOCK • • Poor outcome is associated with: o Absence of meningism o Hypotension o Young age o Coma o Relatively low temperature (<38°C) o Leukopenia o Thrombocytopenia Spontaneous hemorrhage in different parts of the body (pulmonary, gastric, or cerebral) may result from consumption of coagulation factors and thrombocytopenia. CHRONIC MENINGOCOCCEMIA • Rarely recognized – because you may think patient is presenting with other viral illness • Presents as repeated episodes of petechial rash associated with fever, joint pain, features of arthritis, and splenomegaly that may progress to acute meningococcal septicemia if untreated (rarely) o Have high index of suspicion • Relapsing course • Associated with complement deficiencies in some cases or inadequate sulfonamide therapy o In the past Cotrimoxazole (Trimethoprim /Sulfamethoxazole) is used to treat meningitidis infection 💜🥕 • Underacylated lipid A due to an lpxL1 gene mutation which markedly reduces the inflammatory response to endotoxin POSTMENINGOCOCCAL REACTIVE DISEASE • Immune complex disease develops ~4–10 days after the onset of meningococcal disease • Manifestations include a maculopapular or vasculitic rash (2% of cases), arthritis (up to 8% of cases), iritis (1%), pericarditis, and/or polyserositis associated with fever o Condition is very difficult to diagnose • The immune complexes involve meningococcal polysaccharide antigen and result in immunoglobulin and complement deposition with an inflammatory infiltrates in different tissues. • Resolve spontaneously without sequelae • No need to give antibiotics, just give NSAIDS DIAGNOSIS 1. Culture – GOLD STANDARD • Confirm the diagnosis and facilitate public health investigations • Blood cultures are positive in 40% to 75% of cases • CSF 90% of cases 2. Skin biopsy and culture of the rash seen in meningococcemia (with purpuric rashes) shows endothelial necrosis, with meningococci present within the endothelium and thrombi. • Not done if there’s already signs of bleeding and low platelet 3. Real-time PCR analysis of whole-blood samples increases the diagnostic yield by >40%, and results obtained with this method may remain positive for several days after administration of antibiotics. 4. Identification of the organism on throat swabs has no diagnostic value • Never do throat swab even if patient is complaining of throat pain because patient might be dealing with another cause of meningitis, but the throat swab positive for N. meningitidis • Patient can be a carrier and there might be a colonizer in the throat and doesn’t mean that that’s the origin of the meningitis of the patient 5. Immunoassays (EIA/ELISA) are not currently used for diagnosis of meningitis. 6. Latex agglutination tests (LATs) do not differentiate all known Nm serogroups - a rapid test 7. Lateral flow assays (LFA/RDTs) can be used with unprocessed CSF specimens. o Can differentiate 4 Nm serogroups (A, C, W, Y) o MeniningoSpeed (Biospeedia, France) can differentiate five Nm serogroups (A, C, W, X, Y) and is currently under field evaluation. 8. Lumbar puncture to identify and confirm the etiology • CSF features of meningococcal meningitis (elevated protein level and WBC count, decreased glucose level) are indistinguishable from those of other types of bacterial meningitis unless a gram-negative diplococcus is identified. (Gram’s staining is up to 80% sensitive) • CSF antigen testing with latex agglutination is insensitive 7 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria PROBABLE CASES SUSPECTED CASES which N. meningitidis is isolated by culture or PCR from a normally sterile site or purpuric lesions. Pesence of N. meningitidis antigen by immunohistochemistry or latex agglutination A Gram-stain shows Gramnegative diplococci obtained from a sterile site or there is clinical purpura fulminans but a negative blood culture. Risk Factors for Contracting Invasive Meningococcal Disease and Related Mortality: A Systematic Literature Review and Metaanalysis Dubey, et. al., Open Access, March 23,2022 • • • Significant risk in HIV-infected individuals Crowded living environments and passive smoke exposure as risk factors in children and adolescents Older age groups Higher risks of IMD-related mortality with age (25 – 44 years) and serogroup C TREATMENT • Meningococcal disease is potentially fatal and should always be viewed as a medical emergency • Admission to a hospital or health center is necessary. • Isolation of the patient is not necessary. • • • • • • Elevated WBC count and inflammatory markers (e.g., CRP and procalcitonin levels or ESR). Severe meningococcal septicemia, common laboratory findings include: o Hypoglycemia o Acidosis o Hypokalemia o Hypocalcemia o Hypomagnesemia o Hypophosphatemia o Anemia o Coagulopathy Death from meningococcal disease is associated most commonly with hypovolemic shock (meningococcemia) and occasionally with raised intracranial pressure (meningococcal meningitis). Management should focus on the treatment of these urgent clinical issues in addition to the administration of specific antibiotic therapy. Delayed recognition of meningococcal disease or its associated physiologic derangements, together with inadequate emergency management, is associated with poor outcome. CONFIRMED CASES 💜🥕 2015 CDC CASE DEFINICATIONS A clinically compatible case in EMPIRICAL ANTIBIOTIC THERAPY FOR SUSPECTED MENINGOCOCCAL DISEASE • Ceftriaxone 75–100 mg/kg per day [maximum, 4 g/d] • Cefotaxime 200 mg/kg per day [maximum, 8 g/d] in four divided IV doses • Reduced meningococcal sensitivity to Penicillin has been reported widely. Once susceptibilities are known, antibiotics can be changed to penicillin if the isolate has a MIC <0.1 μg/mL. If the MIC is greater than this, a 3rd-gen cephalosporin is preferred. • For patients with a history of anaphylaxis with penicillin or cephalosporin use, chloramphenicol can be used. • Meropenem is also an option, although the rate of crossreactivity with penicillin is between 2% and 3%. DRUG DOSE COMMENTS CEFTRIAXONE 75-100 mg/kg/day PO or IV divided every 6 hrs CEFOTAXIME 200-300 mg/kg/day divided every 6-8 hrs PENICILLIN G 300,000 U/kg/day divided every 4-6 hrs MEROPENEM 120 mg/kg per day CHLORAMPHENICOL 75-100 mg/kg/day PO or IV divided every 6 hrs Although ceftriaxone resistance is seen w/ other Neisseria spp, it is unlikely for meningococcal disease. May be used if the isolate has an MIC of <0.1 μg/mL. Approx 2%-3% of penicillin or cephalosporin allergic patients may crossreact. Approx 2%-3% of penicillin or cephalosporin allergic 8 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria patients may crossreact. Used in penicillin or cephalosporinallergic patients. • • • • • • • Both meningococcal meningitis and meningococcal septicemia are conventionally treated for 7 days, although courses of 3–5 days may be equally effective. No data are available to guide the duration of treatment for meningococcal infection at other foci (e.g., pneumonia, arthritis); antimicrobial therapy is usually continued until clinical and laboratory evidence of infection has resolved. Cultures usually become sterile within 24 h of initiation of appropriate antibiotic chemotherapy. Glucocorticoids for adjunctive treatment remains controversial Therapeutic doses of glucocorticoids are not recommended in meningococcal septicemia, but as replacement doses for patients who have refractory shock in association with impaired adrenal gland responsiveness. Use of activated protein C has been considered in adult sepsis trials; however, trials in pediatric sepsis found no benefit and indicated a potential risk of bleeding complications. The postmeningococcal immune-complex inflammatory syndrome has been treated with NSAID until spontaneous resolution occurs. • • • In one study one-quarter of survivors had psychological disorders. In some investigations, the rate of complications is higher for serogroup C disease than for serogroup B disease. Adverse psychosocial outcomes: reduced quality of life, lowered self-esteem, and poorer neurologic development, including increased rates of attention deficit/hyperactivity disorder and special educational needs. IMMUNITY • Most individuals develop natural immunity to meningococcus in the first 2 decades of life from exposure through nasopharyngeal colonization. • Antibody titers in infants are similar to maternal serum concentrations but decrease by age 6 months. • Increased risk for meningococcal disease - HIV, partial Tcell defects (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia), those with anatomic and functional asplenia, and those who have complement deficiencies. • Acquired complement deficiencies can result from inadequate production of complement components due to liver dysfunction, increased consumption of complement by autoimmune disease such as lupus, or increased excretion by protein-losing diseases, and patients receiving eculizumab therapy. PROGNOSIS • Several prognostic scoring systems • Factors associated with a poorer prognosis are shock; young age (infancy), old age, and adolescence; coma; purpura fulminans; DIC; thrombocytopenia; leukopenia; absence of meningitis; metabolic acidosis; low plasma concentrations of antithrombin and proteins S and C; high blood levels of PAI-1; and a low ESR or C-reactive protein level. • The Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) is probably the best-performing scoring system studied so far. • Fulminant meningococcemia is more likely to result in death or ischemic skin loss than is meningitis GLASSGOW MENINGOCOCCAL SEPTICEMIA PROGNOSTIC SCORE COMPLICATIONS • About 10% die despite the availability of antimicrobial therapy and other intensive medical interventions • Scarring in 10% after necrosis of purpuric skin lesions • Amputations are necessary in 1–2% of survivors • Approximately 5% suffer hearing loss, and 7% have neurologic complications 💜🥕 9 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria maximum 600 mg/dose CIPROFLOXACIN >1 month: 20 mg/kg PO ONCE, maximum 500 mg CEFTRIAXONE <15 years: 125 mg IM ONCE ≥15 years: 250 mg IM ONCE AZITHROMYCIN STEIHM AND DAMROSCH CRITERIA • • • CHEMOPROPHYLAXIS • Should be administered w/in 24 hours of identification of the index patient • Close follow-up evaluation is necessary due to the rapid onset of disease. • Secondary cases usually occur w/in 10 days of infection of the index case. Chemoprophylaxis administered >14 days after exposure to the index case is of limited value and not recommended by the CDC. • Mass chemoprophylaxis is generally not recommended. • Options for prophylaxis include rifampin, ceftriaxone, or ciprofloxacin. o Rifampin is the only agent that has been studied widely, but there may be drug-drug interactions to consider; 4 doses are required. o Ceftriaxone, single dose, >97% effective in eradicating carriage; safe in pregnancy. o Ciprofloxacin also eradicates carriage in a single dose; cannot be used in pregnant women; concerns for resistance o Azithromycin may be used but generally not recommended as 1st line agent. o Oral third-generation cephalosporins are not recommended. • If a patient received therapy with an agent other than a parenteral 3rd gen. cephalosporin, additional chemoprophylaxis is required to reliably eradicate nasopharyngeal carriage before hospital discharge, thereby preventing transmission to close contacts. DRUG RIFAMPIN 💜🥕 DOSE <1 month: 10 mg/kg PO every 12 hrs x 2 days ≥1 month: 20 mg/kg PO every 12 hrs x 2 days, 10 mg/kg PO ONCE, maximum 500 mg Not recommended in pregnancy. Should not be used in areas of Ciprofloxacin resistance. Considered secondline. Used in areas with ciprofloxacin resistance if no other alternative. Outside the African meningitis belt, chemoprophylaxis is recommended for close contacts within the household. In the meningitis belt, chemoprophylaxis for close contacts is recommended in non-epidemic situations. Ciprofloxacin antibiotic is the antibiotic of choice, and ceftriaxone an alternative. 3 TYPES OF VACCINES • Are used during a response to outbreaks, mainly in Africa POLYSACCHARIDE • Not effective before 2 years of VACCINES age • Offer a 3-year protection • Do not induce herd immunity • against N. meningitidis B • Introduced into the routine immunization schedule and used in outbreak response. PROTEIN BASED VACCINE • Protect against meningitis in all ages • Not prevent carriage • Do not lead to herd protection • are used in prevention (into routine immunization and preventive campaigns) and outbreak response • Confer longer-lasting immunity (5 years and more), prevent • Carriage and induce herd immunity POLYSACCHARIDE• Can be used as soon as of one PROTEIN year of age CONJUGATE o Monovalent (A or C) VACCINES o Quadrivalent (A, C, W, Y) o Combination (serogroup C and Haemophilus influenzae type b) • No vaccines available against serogroup X COMMENTS Not recommended in pregnancy. 10 LE3T1 Lecture 3: Medicine II Meningococcal Disease Dr. Elpidio Demetria Defeating meningitis by 2030 – developing a global roadmap • Vision: a world free of meningitis. • Three visionary goals: 1. Eliminate meningitis epidemics 2. Reduce cases and deaths from vaccinepreventable meningitis by 80% 3. Decrease the impact of impairments due to meningitis by 50% 💜🥕 11