Meningococcaemia

Meet the patient

A 19-year-old university student reaches the emergency department at 3 am with fever, aching muscles, and cold hands. An hour ago her rash was a faint pink flush; now there are crops of dark purple spots spreading across her trunk and legs, and a clear drinking glass pressed against them does not blanch them. She is confused, her peripheries are mottled, and her blood pressure is falling. ^[1][2]

Two questions now decide whether she leaves hospital alive: what is this rash? and what do I do in the next fifteen minutes? This is meningococcal septicaemia with purpura fulminans until proven otherwise — antibiotic before the blood culture, ICU now. Everything below exists to make that recognition reflexive. ^[1][3]

The single concept — fever plus a non-blanching rash

Fever plus a non-blanching petechial or purpuric rash is meningococcaemia until proven otherwise. That one sentence is the whole topic. The dermatologist's job here is singular and time-critical: to be the person at the bedside who sees the rash, performs the glass test, and reaches for the antibiotic within the hour. ^[1]

Meningococcal disease is the spectrum of invasive illness caused by Neisseria meningitidis, a gram-negative, oxidase-positive diplococcus carried asymptomatically in the human nasopharynx and spread by respiratory droplets and kissing contact. It causes two overlapping phenotypes — meningococcal meningitis (meningeal inflammation, often without a rash) and meningococcal septicaemia, conventionally called meningococcaemia, with the characteristic rash and septic shock. About half of patients show both at once. ^[2][5][6]

The dermatological stakes are two feared phenotypes. Purpura fulminans is DIC localised to the dermal microvasculature — haemorrhagic infarction of skin, gangrene of digits and limbs, amputation. Waterhouse-Friderichsen syndrome is bilateral adrenal haemorrhage layered on septic shock. A rare, indolent chronic meningococcaemia runs for weeks with low-grade fever, arthralgia and an evanescent rash, and is easily mistaken for a viral exanthem or gonococcaemia. ^[3][7]

The mantra for this topic: fever plus a non-blanching rash — antibiotic before the blood culture. If you carry one line out of this page, carry that one. ^[1]

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Two axes — clinical syndrome and capsular serogroup

Meningococcal disease is classified on two axes — clinical syndrome and capsular serogroup — because both decide management and prevention. ^[1]

Clinically, disease splits into meningitis alone (best prognosis), septicaemia with or without purpura fulminans (worst prognosis), and the mixed picture in about half. A small minority present as chronic meningococcaemia or as focal disease — arthritis, pericarditis, pneumonia, conjunctivitis, urethritis. ^[2][5]

Twelve capsular serogroups are recognised; six are clinically important (A, B, C, W135, X, Y). The polysaccharide capsule is the key virulence factor and the principal vaccine antigen, so serogroup drives epidemiology, outbreak control, and vaccine choice. ^[4]

Epidemiology — where, and whom

Meningococcal disease is global but geographically patterned, and the high-risk groups are exactly the viva staples. The highest endemic burden sits in the sub-Saharan African meningitis belt — a swath from Senegal to Ethiopia — where dry-season epidemics, historically serogroup A and increasingly W135, C and X, reach attack rates of 1000 per 100,000. ^[4]

Outside the belt, incidence in high-income countries is low — about 0.5 to 1 per 100,000 each year — but punctuated by outbreaks in semi-closed communities: university dormitories, military barracks, the Hajj, refugee camps. ^[2][4]

Age distribution is bimodal: a large peak in children under 5 years (highest under 1), and a second peak in teenagers and young adults aged 15 to 19, who carry the organism most often — up to 30 to 50 percent in some closed cohorts, against about 10 percent in the general population. ^[2]

The decisive host risk factors are defects in meningococcal clearance. Deficiency of the terminal complement pathway — C5, C6, C7, C8 or C9, which together form the membrane attack complex that lyses N. meningitidis — raises the risk of invasive disease 7,000- to 10,000-fold and predisposes to recurrent episodes. Properdin deficiency (X-linked) and factor D deficiency cause particularly fulminant disease. ^[11]

The monoclonal anti-C5 antibodies eculizumab and ravulizumab — used for paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, and some refractory myasthenia or ANCA-vasculitis indications — pharmacologically reproduce this defect and carry a labelled warning for meningococcal infection despite vaccination. ^[11]

Other risk factors: anatomical or functional asplenia (sickle-cell disease, post-splenectomy, congenital), HIV, active and passive smoking, viral respiratory co-infection that damages mucosa, and concurrent influenza. ^[2]

Pathophysiology — why the rash, the shock, and the clock

Understanding the cascade explains the rash, the shock, and why the antibiotic comes before any test. ^[3][6]

1. Colonisation. N. meningitidis colonises the nasopharyngeal mucosa using type IV pili and the Opa and Opc adhesins, which bind epithelial CD66 and CEA receptors. Most carriers are asymptomatic; invasion is the exception, favoured by viral co-infection, smoking, low mucosal IgA, and host susceptibility. ^[6]

2. Invasion and bacteraemia. The organism crosses the mucosal barrier — aided by its IgA1 protease, which cleaves secretory IgA — and enters the bloodstream. The antiphagocytic capsular polysaccharide and factor-H-binding protein (fHbp), which recruits complement factor H to switch off opsonisation, let it evade innate immunity. ^[6]

3. Endotoxin-driven cytokine storm. N. meningitidis sheds outer-membrane lipooligosaccharide (LOS, the meningococcal endotoxin) as membrane blebs. LOS binds the TLR4, MD-2 and CD14 complex on monocytes, macrophages and endothelial cells, triggering release of TNF-alpha, IL-1, IL-6 and IL-8. The cytokine storm drives fever, endothelial leak, vasodilatation, myocardial depression, and shock. ^[3]

4. DIC and purpura fulminans. LOS and cytokine-activated endothelium express tissue factor, generating thrombin; at the same time protein C, protein S and antithrombin are consumed and the protein C pathway is dysregulated. The net effect is widespread microvascular thrombosis with consumption of platelets and clotting factors — DIC. In the skin, dermal capillary and venule thrombosis produces haemorrhagic infarction: the lesions march from petechiae to purpura to ecchymoses to necrotic black eschars. This is purpura fulminans — DIC made visible — and in the limbs it ends in gangrene and amputation. ^[3][7]

5. Meningeal invasion. Bacteraemic organisms cross the blood-brain barrier at the choroid plexus, seeding the subarachnoid space — where complement and immunoglobulin are scarce and phagocytosis is inefficient. Meningeal inflammation produces neck stiffness, raised intracranial pressure, and the CSF picture of pyogenic bacterial meningitis. ^[5]

6. Adrenal haemorrhage — Waterhouse-Friderichsen. DIC within the richly vascular adrenal cortex causes bilateral adrenal haemorrhage, acute adrenal insufficiency, and refractory vasodilatory shock. This is Waterhouse-Friderichsen syndrome — bilateral adrenal haemorrhage layered on septic shock — the classic catastrophe of fulminant meningococcaemia. ^[1]

A disease measured in hours

The disease evolves over hours, and the earliest phase masquerades as a viral illness — which is why a deliberate search for the rash is non-negotiable in any febrile, unwell patient. ^[1][2]

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The rash — the dermatological hallmark

The rash is the single most important physical sign, and the glass test confirms it. It begins as petechiae (pinpoint non-blanching macules), evolves into purpura (larger confluent areas), and in severe cases into ecchymoses with central necrosis. Distribution favours the trunk and lower limbs, but any site, including mucous membranes and conjunctivae, can be involved. ^[10]

The glass test — pressing a clear glass or tumbler firmly against the lesion and watching for blanching — is positive in meningococcaemia: the lesions do not fade, because they are extravasated blood and microvascular thrombosis, not inflammatory vasodilatation. A febrile patient whose rash does not blanch under glass is treated as meningococcaemia. ^[1]

The classic trap: up to a third of patients have a blanching maculopapular rash early on, indistinguishable from a viral exanthem. A normal-looking skin, or a rash that blanches, does not exclude meningococcaemia in the first hours — examine the whole skin repeatedly, and treat on suspicion. ^[1]

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Meningococcal meningitis — about half

When meningeal seeding dominates, the patient has the classic triad of fever, neck stiffness and altered mental status — all three in roughly half, at least two in nearly all. Headache is severe and diffuse; photophobia and Kernig and Brudzinski signs are present. The rash may be absent, sparse, or prominent. Seizures, focal neurology and a falling conscious level signal raised intracranial pressure or a complication — cerebral oedema, venous sinus thrombosis, empyema. ^[5]

Meningococcal septicaemia — the dangerous one

The septicaemic phenotype is the most dangerous. High fever, cold peripheries with mottled or ashen skin, tachycardia, tachypnoea, hypotension and oliguria reflect septic shock and evolving multi-organ failure. Purpura fulminans is DIC made visible: large areas of purpuric skin become necrotic, digits and limbs become ischaemic, and amputation may become unavoidable. Waterhouse-Friderichsen syndrome — bilateral adrenal haemorrhage with refractory shock — may supervene. ^[1][3][7]

Chronic meningococcaemia — the missed one

A distinct, indolent phenotype that lasts weeks and is easily dismissed. Intermittent low-grade fever, arthralgia or arthritis, myalgia, and an evanescent maculopapular or petechial rash that waxes and wanes. Blood cultures or PCR are positive, but the illness mimics gonococcaemia, Henoch-Schönlein purpura, or a viral exanthem. Left untreated it can seed the meninges or escalate to fulminant septicaemia, so it is treated as invasive disease. ^[2]

Differential diagnosis — tempo is the discriminator

The differential of fever plus a petechial, purpuric or vasculitic rash is broad — but a febrile patient with a non-blanching rash is managed as meningococcaemia while the rest is considered in parallel. ^[1][10]

The bedside discriminator is tempo and systemic toxicity. Meningococcaemia evolves over hours with mounting shock and DIC; the vasculitides and thrombocytopenias run over days to weeks. A non-blanching rash in a febrile, unwell patient is nevertheless treated as meningococcaemia while the work-up proceeds. ^[1]

Bedside assessment — in parallel with the antibiotic, never in series

A focused, rapid assessment runs in parallel with the first antibiotic — never in series with it. ^[1][5]

Rash. Examine the whole skin in good light — conjunctivae, palate, ears, soles and dependent areas. Characterise each element: petechia (under 3 mm), purpura (over 3 mm), ecchymosis (over 1 cm), necrotic eschar. Perform the glass test. Look for dusky, map-like purpura with grey-black centres signalling purpura fulminans, and for mottling or cold, ischaemic digits indicating limb-threatening DIC. ^[1]

Meningeal signs. Kernig sign — with the patient supine and the hip flexed at 90 degrees, the knee cannot be passively extended without pain or resistance. Brudzinski sign — passive flexion of the neck produces involuntary flexion of the hips and knees. Jolt accentuation — the baseline headache worsens on rapid horizontal rotation of the head two to three times per second — has high sensitivity for meningeal irritation. Head-holding, tripoding and photophobia are supportive. ^[5]

Septic screen. Vital signs (temperature, heart rate, respiratory rate, blood pressure, capillary refill, oxygen saturation), conscious level (GCS), and signs of shock — mottled or cold skin, prolonged capillary refill, weak pulses, oliguria, hypotension (a late sign in children). Identify any source (otitis, sinusitis, pneumonia) and look for stigmata of risk: splenectomy scar, Hickman line, known complement deficiency, eculizumab. ^[1]

Skin biopsy or lesion scrape. A Gram stain of a petechial scraping or a punch biopsy of an early purpuric lesion can show gram-negative diplococci within neutrophils — a rapid bedside confirmation that must not delay treatment. ^[1]

Histopathology — thrombosis, not vasculitis

The histopathology mirrors the vascular catastrophe, and is itself diagnostic when culture is negative or the patient is pre-treated. ^[3][7]

Early petechial lesion. A punch biopsy shows dermal capillaries and post-capillary venules occluded by fibrin thrombi, with extravasated red cells and a neutrophil-predominant infiltrate around and within vessel walls — described as both thrombotic and leucocytoclastic. Unlike classical small-vessel vasculitis, the dominant event is intravascular thrombosis, not immune-complex vessel-wall necrosis, reflecting the DIC substrate. Gram stain may reveal gram-negative diplococci within endothelial cells and neutrophils. ^[3]

Purpura fulminans. The fully evolved lesion shows full-thickness dermal and often subcutaneous infarction with diffuse microvascular thrombosis, haemorrhage, and a confluent necrotic epidermis that detaches as a black eschar. A sharp border often separates necrotic from viable skin. Adnexal structures, subcutaneous fat and even muscle may be infarcted — explaining the depth of tissue loss that forces debridement and grafting. ^[7]

Adrenals — Waterhouse-Friderichsen. At post mortem the adrenal glands are enlarged, boggy and uniformly haemorrhagic, with cortical-cell necrosis and a preserved medulla — the anatomical basis for acute mineralocorticoid and glucocorticoid failure layered on top of septic shock. ^[1]

Why histology matters for the dermatologist. A biopsy of an atypical lesion settles the differential between meningococcal purpura, post-infectious IgA vasculitis, and thrombotic microangiopathy: thrombosis without immune-complex deposition favours infection-associated purpura fulminans, while IgA deposition on immunofluorescence favours Henoch-Schönlein purpura. Gram stain and PCR on biopsy tissue confirm N. meningitidis even after antibiotics have sterilised the blood. ^[3][7]

Investigations — confirm, but never delay the antibiotic

Investigations confirm the diagnosis but never delay the first antibiotic. The hierarchy is fixed: treat, then culture, then confirm by PCR. ^[5]

CSF in meningococcal meningitis

The CSF pattern is that of pyogenic bacterial meningitis. Bacterial meningitis has characteristic effects on the CSF white-cell count, CSF protein level, and the CSF:serum glucose ratio — a neutrophil-predominant pleocytosis with raised protein and a reduced glucose ratio — and adjunctive PCR testing helps differentiate bacterial from viral causes. N. meningitidis is one of the commonest causes of community-acquired bacterial meningitis; CSF culture can identify the causative organism and its antibiotic sensitivities. ^[19][5]

When to defer the lumbar puncture

LP is deferred — and empirical antibiotics plus a CT head given instead — whenever it is unsafe. Defer in the presence of signs of raised intracranial pressure (falling GCS, focal neurology, seizures, papilloedema, Cushing triad), coagulopathy (platelet count under 100 × 10⁹/L, INR over 1.4, or known DIC), or septic shock in which positioning and sedation are unsafe. Antibiotics are never withheld to obtain CSF; PCR later confirms the organism. ^[5]

Management — the resuscitation phase

Meningococcal disease is a time-critical emergency. The resuscitation bundle runs in parallel: recognise, give antibiotics immediately, secure ABC, investigate, escalate. ^[1][5]

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Step 1 — Recognise

Fever with a non-blanching petechial or purpuric rash in an unwell patient is meningococcaemia until proven otherwise. The glass test confirms non-blanching. Do not wait for a classical picture — an early blanching maculopapular rash, or even an absent rash, still warrants treatment if suspicion is high. ^[1]

Step 2 — Immediate antibiotic, before any test or transfer

The first antibiotic is given before blood cultures, lumbar puncture, CT or transfer — every time. ^[1]

• Pre-hospital, community: give parenteral antibiotics at once when meningococcal disease is suspected, before hospital transfer — primary-care guidance advises antibiotics, preferably an intravenous cephalosporin, at this stage; a single intramuscular ceftriaxone dose is an accepted pre-admission regimen. ^[1][18]
• Hospital, first hour: an IV cephalosporin (ceftriaxone or cefotaxime) immediately on admission; do not wait for blood cultures, LP, or imaging. Early antibiotic treatment improves outcome, and penicillin-intermediate and resistant strains are increasing worldwide, which underpins cephalosporin-based empiric therapy. ^[1][8]
• Why speed: meningococcal disease begins suddenly and death can follow within hours — the justification for treating on suspicion before transfer or confirmation. ^[18]

Step 3 — ABC and supportive care

Airway, breathing and circulation run alongside the antibiotic — never after it. ^[1][5]

• Airway and breathing: structured assessment and regular review of airway, breathing and circulation, escalating to intubation and ventilation for coma or respiratory failure. ^[1]
• Circulation: establish IV access; for septic shock give crystalloid boluses with frequent reassessment — but in resource-limited settings give them cautiously: in the FEAST trial, boluses of 20 to 40 mL per kilogram of saline or albumin in African children with severe infection increased mortality compared with no bolus. ^[1][13]
• Refractory shock: vasopressors with, for shock that remains unstable despite adequate fluids and vasopressors, low-dose corticosteroids. ^[14]

Fluid resuscitation in detail. Give crystalloid boluses with frequent reassessment of perfusion and respiratory status. In resource-limited settings — the FEAST trial in African children with severe infection — boluses of 20 to 40 mL per kilogram of 5 percent albumin or 0.9 percent saline increased 48-hour mortality versus no bolus, with excess deaths from pulmonary oedema and raised intracranial pressure; where intensive-care monitoring is limited, give fluids cautiously and reassess after every aliquot. For septic shock with relative adrenal insufficiency, low-dose hydrocortisone 50 mg IV every 6 hours plus fludrocortisone 50 micrograms daily improved 28-day survival in corticotropin non-responders. ^[13][14]

Step 4 — Investigations, after the first antibiotic

Bloods and cultures come after the antibiotic, never before it. Blood cultures (drawn before antibiotics if achievable without delay), blood and CSF PCR for N. meningitidis, FBC, coagulation and DIC screen, U&E, LFTs, CRP, lactate, glucose and blood gas. LP is performed only if safe; otherwise defer and rely on PCR. ^[5]

Step 5 — Escalate and protect contacts

Admit to ICU for shock, coma, purpura fulminans or respiratory failure, and begin contact prophylaxis within 24 h. Prophylaxis goes to household, kissing and secretion-exposed contacts, and the case is notified to public health. ^[2]

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Management — definitive and stepwise

Directed antibiotic therapy

Once N. meningitidis is confirmed, directed therapy continues a third-generation cephalosporin course. ^[1]

• Ceftriaxone or cefotaxime IV — cephalosporins are the mainstay of therapy; a single intramuscular ceftriaxone dose was as effective and safe as long-acting chloramphenicol in pre-admission treatment, and increasing penicillin resistance worldwide favours cephalosporins. ^[18][8]
• Where cephalosporins are unavailable: intramuscular chloramphenicol alone is comparable with intravenous use and can be given as a shorter course followed by an oral course. ^[16]
• Adjunctive dexamethasone 0.15 mg/kg six-hourly for 4 days (in adults, 10 mg every 6 hours for four days), given 15 to 20 minutes before or with the first antibiotic dose, reduces unfavourable outcome and mortality in bacterial meningitis, with the greatest benefit in pneumococcal meningitis. ^[16][12]

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Purpura fulminans — DIC and skin or limb salvage

Purpura fulminans is managed in ICU with haematology and surgery side by side. ^[3][7]

• DIC support: the fundamental lesion is failure of the anticoagulant protein C pathway; treatment centres on repletion of natural circulating anticoagulants, therapeutic anticoagulation in selected patients, and optimised transfusion support — and some interventions are specifically recommended against. ^[7]
• Thrombosis over shock: patients who survive the first 24 to 72 hours often die of complications of unchecked thrombosis rather than shock — anticoagulant pathway support continues after stabilisation. ^[7]
• Tissue loss: survivors are usually left with severe scarring and tissue loss; surgical and reconstructive needs are anticipated from the outset. ^[7]
• Adrenal support: for Waterhouse-Friderichsen with septic shock, low-dose hydrocortisone 50 mg IV every 6 hours plus fludrocortisone improved 28-day survival in septic shock with relative adrenal insufficiency (corticotropin non-responders). ^[14][21]

Chemoprophylaxis of close contacts

Carriage eradication protects contacts, who are at up to 1,000-fold higher risk than the baseline population in the days after exposure. Give prophylaxis within 24 h (effective up to 14 days) to household contacts, kissing contacts, and healthcare workers exposed to respiratory secretions — intubation without a face mask, mouth-to-mouth resuscitation. ^[2][5]

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The index case also receives chemoprophylaxis before discharge if treated with an agent that does not eradicate carriage — for example benzylpenicillin. Ceftriaxone itself eradicates carriage, so the index case on ceftriaxone does not routinely need separate prophylaxis. ^[2]

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Vaccination — the cornerstone of prevention

Vaccination is the cornerstone of prevention and has reshaped serogroup epidemiology. ^[4][9]

• MenACWY (quadrivalent conjugate vaccine) — against serogroups A, C, W135 and Y; conjugation to a carrier protein produces T-cell-dependent memory and reduces carriage, generating herd immunity. The UK MenC programme (from 1999) and the shift to MenACWY (from 2015, in response to rising W135) drove dramatic declines in those serogroups. ^[4]
• MenB (4CMenB, Bexsero; or MenB-FHbp, Trumenba) — the serogroup B polysialic-acid capsule is poorly immunogenic because it mimics human neural cell-adhesion molecules, so MenB vaccines use subcapsular proteins (factor-H-binding protein, NadA, NHBA, PorA). 4CMenB entered universal infant schedules in 2015 and is effective against the dominant serogroup in developed countries. ^[9]
• MenA (MenAfriVac and conjugate equivalents) — mass campaigns across the African meningitis belt have nearly eliminated serogroup A epidemics there. ^[4]
• Serogroup X has no widely licensed conjugate vaccine and remains a surveillance priority in Africa. ^[4]

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Public health and outbreak control

Every case of confirmed or suspected meningococcal disease is notifiable to public health. The unit of prevention is the close contact: household members, kissing contacts, and healthcare workers exposed to respiratory secretions during airway manoeuvres. All receive chemoprophylaxis within 24 h of the index case's onset. ^[2]

Clustering — two or more linked cases in a school, barracks or dormitory within a short window — triggers enhanced surveillance, wider prophylaxis of the defined at-risk group, and, depending on serogroup, vaccination: MenACWY for A, C, W or Y clusters, MenB for serogroup B clusters. Travellers to the Hajj and to the sub-Saharan meningitis belt require a recent MenACWY certificate. ^[4]

Specific subtypes and scenarios

Purpura fulminans

The most catastrophic phenotype: DIC-driven cutaneous and visceral microvascular thrombosis with rapidly spreading purpuric skin necrosis, limb ischaemia, and multi-organ failure. Mortality is 30 to 50 percent; survivors frequently need amputation and skin grafting and bear major scarring. Management combines aggressive antibiotic therapy, DIC support (FFP, cryoprecipitate, platelets), ICU resuscitation, and early surgical involvement. ^[3][7]

Waterhouse-Friderichsen syndrome

Waterhouse-Friderichsen syndrome is a severe complication of meningococcal meningitis involving endotoxin-mediated adrenal damage — it presents as shock with a widespread non-blanching purpuric rash, multi-organ failure and high mortality, and is treated with fluid resuscitation, empiric antibiotics, vasopressor support and hydrocortisone alongside intensive care. For septic shock with relative adrenal insufficiency, low-dose hydrocortisone 50 mg IV every 6 hours plus fludrocortisone improved 28-day survival in corticotropin non-responders. ^[21][14]

Chronic meningococcaemia

Weeks of intermittent low-grade fever, arthralgia, myalgia and an evanescent rash — blood culture or PCR is positive. It mimics gonococcaemia, subacute endocarditis and IgA vasculitis. Treat as invasive disease with ceftriaxone; untreated it may seed the meninges or escalate to fulminant septicaemia. ^[2]

Serogroup-specific patterns

• W135 disease (post-Hajj strains) tends to be more fulminant and to present atypically — joint and gastrointestinal presentations.
• Serogroup Y more often affects older adults and may present as pneumonia.
• Serogroup A remains the epidemic strain of the meningitis belt, now much reduced by MenAfriVac. ^[4]

Complications and the preventable-death list

The preventable-death list — these are the patients who die, and they die avoidably. ^[1][5]

• Delaying the first antibiotic for blood cultures, LP, CT or hospital transfer — mortality rises about 7 percent per hour.
• Sending a sick child home with a viral rash without examining the whole skin in good light and performing a glass test.
• Performing an LP in coagulopathy or raised ICP — spinal epidural haematoma and herniation.
• Forgetting chemoprophylaxis of household and kissing contacts within 24 h.
• Under-resuscitating septic shock.
• Missing atypical presentations — sore throat only, arthritis, isolated pneumonia — especially in asplenic, complement-deficient, or eculizumab-treated patients. ^[1]

Comorbidities — what to screen for in the host and the survivor

Meningococcal disease is both a consequence and a cause of comorbidity. On the risk side, the host conditions that permit invasion are themselves the comorbidities to screen for: terminal complement (C5 to C9) and properdin deficiency (test with a CH50 or AP50 assay in any patient with recurrent or familial disease, or a first episode with an unusual serogroup), functional or anatomical asplenia (sickle-cell disease, post-splenectomy, congenital), HIV, and the anti-C5 monoclonals eculizumab and ravulizumab. Identifying one of these changes long-term management — vaccination, standing emergency antibiotics, and patient education — and may prompt family screening for complement deficiency. ^[11]

On the consequence side, survivors acquire lasting morbidity that must be actively managed: sensorineural hearing loss (universal audiology referral), chronic adrenal insufficiency after Waterhouse-Friderichsen (short Synacthen testing where persistent hypotension, fatigue or electrolyte disturbance suggests it), renal impairment after ATN, post-ICU critical-illness weakness and neuropathy, amputation-related and skin-graft disability, and psychological morbidity — PTSD, anxiety, depression — in survivors and their families. A structured post-discharge follow-up — audiology, endocrine assessment where indicated, rehabilitation, psychology, and prosthetics for amputees — is part of definitive care, not an optional add-on. ^[1]

Prognosis and disposition

Overall mortality is about 10 percent, rising to 30 to 50 percent in purpura fulminans and up to 40 percent in septicaemic shock. Meningitis without septicaemia carries the best prognosis. Poor prognostic markers are a rapidly progressive purpura, shock at presentation, low GCS, high bacterial load (low PCR cycle threshold), thrombocytopenia, low fibrinogen, high lactate, renal failure, and age extremes. ^[1][3]

About 20 percent of survivors have long-term sequelae: sensorineural hearing loss, amputation, skin scarring, neurological and cognitive deficit, and psychological trauma. Audiology before discharge is mandatory. ^[1]

Disposition. ICU for shock, coma, purpura fulminans or respiratory failure; the ward once stable and afebrile on directed therapy; discharge after completing or arranging the antibiotic course, audiology, and a rehabilitation plan for amputees and grafted patients. Public-health follow-up coordinates contact prophylaxis and any outbreak vaccination. ^[2]

Special populations

The thresholds shift in these groups — know them cold. ^[1]

• Children: weight-based antibiotic dosing; resuscitate septic shock with cautious boluses and frequent reassessment — in the FEAST trial of African children with severe infection, boluses of 20 to 40 mL per kilogram of saline or albumin increased mortality versus no bolus. ^[13]
• Complement C5 inhibition (eculizumab): meningococcal disease incidence is 1,000- to 2,000-fold higher than baseline; disease occurs despite vaccination, with many cases caused by nongroupable strains; vaccinate before beginning treatment, consider antimicrobial prophylaxis for the duration of treatment, and insist on heightened awareness and rapid treatment of any compatible symptoms. ^[17]
• Adjunctive dexamethasone in children and adults with bacterial meningitis: 0.15 mg/kg six-hourly for 4 days (adult trials: 10 mg every 6 hours for four days), before or with the first antibiotic dose. ^[16][12]

Evidence, guidelines and regional differences

These are the policies, vaccines and controversies the examiner names. ^[1][5]

• Pre-hospital penicillin — the UK general-practitioner policy of giving IV or IM benzylpenicillin before transfer underpins the first-hour antibiotic bundle and is supported by observational evidence of reduced mortality. ^[1]
• 4CMenB (Bexsero) — a multi-component, protein-based vaccine that overcame the poor immunogenicity of the serogroup B capsule; a decade of real-world data shows effectiveness against infant MenB disease. ^[9]
• MenACWY conjugate and MenC — conjugate vaccines reduce carriage and confer herd immunity; the UK MenC programme (1999) and the 2015 shift to MenACWY in response to rising W135 produced steep declines. ^[4]
• Surviving Sepsis, NICE, ANZ — the hour-1 bundle (antibiotics, lactate, cultures, fluids, vasopressors) applies directly to meningococcal septicaemia. ^[5]
• Antibiotic resistance — penicillin intermediate-susceptibility and, rarely, ciprofloxacin resistance have emerged in N. meningitidis; surveillance guides local prophylaxis and therapy choices. ^[8]
• Complement-directed therapy risk — eculizumab and ravulizumab carry a boxed warning for meningococcal infection; vaccinate (MenACWY plus MenB) and give prophylaxis, yet infections still occur. ^[11]
• Controversies: the benefit of dexamethasone in isolated meningococcal meningitis is limited versus pneumococcal; the roles of heparin and protein C in purpura fulminans are unsettled; and activated protein C has no role after its withdrawal. ^[3][7]

Exam pearls — the memory devices

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Ward-round test

A 19-year-old has fever, myalgia and a rapidly spreading non-blanching purpuric rash with cold peripheries. What is the single most important first action, and what must NOT delay it?ShowHide

Give parenteral antibiotics immediately — IV or IM benzylpenicillin or an IV cephalosporin — before blood cultures, lumbar puncture, CT, or hospital transfer: meningococcal disease begins suddenly and death can follow within hours. This is meningococcal septicaemia with purpura fulminans — activate ICU and prepare for shock resuscitation. ^[1][18]

An unwell child has rapidly spreading purpura, hypotension and mottled skin. What two parallel priorities save the limb and the life?ShowHide

This is purpura fulminans — DIC made visible: a highly thrombotic subtype of DIC driven by failure of the protein C anticoagulant pathway. Run two priorities in parallel: haematology-guided DIC support — repletion of natural circulating anticoagulants, therapeutic anticoagulation where indicated, and optimised transfusion support — and immediate ICU resuscitation with antibiotics and circulatory support. Survivors are usually left with severe scarring and tissue loss, and those surviving the first 24 to 72 hours often die of unchecked thrombosis rather than shock. ^[3][7]

Your patient on eculizumab for PNH phones with fever and a sore throat, no rash yet. What do you do, and why is the threshold different?ShowHide

Treat as meningococcaemia now — start parenteral antibiotics immediately and do not wait for a rash. Eculizumab, a terminal complement inhibitor, is associated with a 1,000- to 2,000-fold increased incidence of meningococcal disease, and disease occurs despite vaccination — many cases are caused by nongroupable strains. Vaccinate with meningococcal vaccines before beginning treatment; some providers recommend antimicrobial prophylaxis for the duration of eculizumab treatment, but heightened awareness, early care seeking and rapid treatment of any compatible symptoms remain essential regardless of vaccination or prophylaxis status. ^[17]

References21ShowHide

1. [1]Rajapaksa S, Starr M. Meningococcal sepsis Aust Fam Physician, 2010.PMID 20485712
2. [2]Vaz LE. Meningococcal Disease Pediatr Rev, 2017.PMID 28364047
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