Meningococcal infection: causes, symptoms, diagnosis, treatment, and prevention

Meningococcal infection has three clinical manifestations: meningitis, acute meningococcemia, and chronic meningococcemia, all of which have typical skin manifestations often important for diagnosis.


Causes

Meningococcus, also known as Neisseria meningitides, is a member of Neisseria family and is a Gram-negative aerobic coccus, with 13 serotypes. Human diseases are mostly caused by 5 of them, that is, serogroup A, B, C, W135, and Y.


Signs and Symptoms

Meningitis and acute meningococcemia

Initial symptoms are fever, headache, nausea, vomiting, and upper respiratory symptoms, followed by deliration and coma. Patients with acute meningitis have meningeal irritation symptoms such as neck stiffness, positive results in craniocervical flexion test and straight leg raise test, with or without splenomegaly and rash. Skin lesions are often pleomorphic but mainly petechiae, which is often the basis for early diagnosis. Transient tiny erythema may occur prior to petechiae. Petechiae are small, filthy, and irregular in shape, with slightly raised center, with or without grayish white blisters or pustules. Gram-negative meningococcus can be found by taking serum smears from the center of the skin lesion. Skin lesions occur mainly in the trunk or limbs, followed by the face, palm and sole, and conjunctiva. Most skin lesions are asymmetrical. In fulminant patients, skin and mucous membrane of the whole body can develop quickly increasing generalized petechiae and ecchymoses, rapidly fusing with each other, and necrosis can occur, which is called Waterhouse-Friderichen syndrome.

The total count of white blood cells and neutrophils is increased. Cerebrospinal fluid pressure is increased. Cerebrospinal fluid is turbid and puruloid, with increased cells, mostly neutrophils, with decreased sugars and chlorides, with significantly increased proteins. Meningococcus can be found in petechiae smear, cerebrospinal fluid smear or culture, and blood culture.

Chronic meningococcemia

Obvious clinical symptoms often occur few weeks to months after onset, and periodic fever is present. Fever may be accompanied by muscle soreness, joint pain, mild headache, loss of appetite, weight loss, and various rashes. Skin lesions often occur in painful joints or areas of compression. The body temperature drops after several days, and skin lesions often regress after body temperature drops. However, fever occurs every few weeks or months, and various skin lesions occur during fever.

Various skin lesions include:

  • Grayish white to rosy spots
  • Nodular erythematous lesions, mainly in the lower leg, with subjective pain
  • Various petechiae, with or without small blisters or pustules in the center
  • Hemorrhagic spots surrounded by grayish red halos
  • Large ecchymoses with a grayish blue center
  • Deep, hemorrhagic, painful nodules

Histopathology

Acute meningococcemia

Thrombosis composed of fibrous proteins and platelets in the dermis beneath the petechiae and ecchymoses is visible. Vascular endothelial swelling and damaged or even necrotic blood vessel walls can be seen, and different sized hemorrhagic spots in the tissue are present. In addition, severe vasculitis and many neutrophils and nuclear dusts can be seen in the dermis. Many Gram-negative meningococci can be found inside and outside the vascular endothelial cells and neutrophils.

Chronic meningococcemia

The pathological changes of chronic meningococcemia are completely different from those of acute meningococcemia. Bacteria are absent in the skin lesion and cannot be found even with direct fluorescence test, and thrombosis or necrosis is absent. Perivascular intense lymphocyte infiltration and mild neutrophil infiltration are present. Localized hemorrhage and some neutrophils around the blood vessels in petechiae can be seen. Fibrinoid substances in the blood vessel walls are present, which is similar to those of allergic vasculitis.


Diagnosis

Meningitis and acute meningococcemia

On the basis of sudden high fever, headache, vomiting, and mental changes in the epidemic areas, petechiae in the skin and mucous membranes, and meningeal irritation symptoms, preliminary diagnosis can be provided.

Based on meningococci found in blood and cerebrospinal fluids, definitive diagnosis can be provided.

Chronic meningococcemia

Diagnosis can be provided on the basis of intermittent fever, rash, joint pain, and result of blood culture.


Treatment

For suspected meningococcal infections with normal immune function, antibacterial therapy is required ahead of results of culture. The most common medication is the third generation cephalosporins, such as cefotaxime 2g IV 3 times a day, or ceftriaxone 2g IV twice a day, combined with vancomycin 500 - 750mg IV 4 times a day or 1g IV twice or 3 times a day. For patients with low immune function or aged >50 years, the possibility of infection with Listeria monocytogenes should also be considered. Therefore, it is necessary to add ampicillin 2g IV 4 times a day.

Once Neisseria meningitidis is definitively diagnosed, the best treatment can be switched to ceftriaxone 2g IV q12h, penicillin 40,000 units IV 6 times a day.

Glucocorticoids can reduce the incidence of neurological complications in children and adults. Glucocorticoids should be used before or during antibiotic treatment. The dose of dexamethasone is 0.15 mg/kg in children and 10mg in adults IV 6 times a day for 4 days.


Prevention

Antibiotic prevention

Persons in close contact with patients with meningitis have an increased risk of infection and therefore need to receive prophylactic antibiotic treatment.

Options include:

  • Rifampicin 600mg in adults, 10mg/kg in neonates aged > 1 month, 5mg/kg in neonates aged < 1 month, twice a day for 2 days
  • Ceftriaxone 250mg in adults, 125mg in children aged <15 years, IV in a single dose
  • Fluoroquinolones limited to adults, such as ciprofloxacin or levofloxacin 500mg, or ofloxacin 400mg in a single dose

Azithromycin is not recommended for routine use, but recent studies have confirmed that preventive effects of azithromycin 500mg are equivalent to rifampicin. Therefore azithromycin can be an alternative.

Vaccinations

MenACWY-D, MenACWY-CRM, and Hib-MenCY-TT vaccines are administered intramuscularly, and MPSV4 is administered subcutaneously. Individual doses of all vaccines are 0.5 mL. In persons aged 2 through 55 years, MenACWY and MPSV4 vaccines can be administered concomitantly with other vaccines, but at a different anatomic site, if feasible.

In children aged 2 through 18 months, Hib-MenCY-TT can be administered concomitantly with other vaccines, but at a different anatomic site, if feasible. In children aged 9 through 23 months, MenACWY-D can be administered with other vaccines concomitantly in healthy children at different anatomic sites, if feasible. Children with asplenia should not receive MenACWY-D concomitantly with PCV13; if MenACWY-D is used in persons with asplenia, it should be administered at least 4 weeks after completion of all PCV13 doses.