Bacterial Meningitis: History of Diagnosis and Treatment

Meningococcal meningitis is a potentially fatal bacterial infection of the brain and surrounding tissues that has been responsible for significant morbidity and mortality for hundreds of years. Today, sporadic and deadly outbreaks still occur, despite effective therapeutics and available vaccines. What is the story of meningococcal meningitis, and how has the disease continued to prevail despite technological advancements?

Meningococcal Disease Presentation

Meningococcal meningitis is caused by the organism Neisseria meningiditis, a gram-negative coccobacillus that exclusively infects humans. Approximately 10% of the population will be carrying the organism in their oropharynx (middle part of the throat) at any given time, and colonization of the oropharynx always precedes infection—a factor that likely contributed to outbreaks during the 19th century, when people were often living in close quarters or regular close contact with one another.

The 2 most common types of meningococcal disease are meningitis, an infection of the lining of the brain and spinal cord, and bloodstream infection (also known as meningococcemia), which often leads to sepsis, the body's extreme response to infection. Both types of infection can ultimately lead to death; meningococcal disease has a relatively high fatality rate (10-15%), even with appropriate antibiotic treatment.

Although meningococcal disease can affect anyone, some populations are more at risk, including babies younger than 12 months old, adolescents and young adults. Typical symptoms of meningitis include headache, stiff neck, fever, confusion, light sensitivity and nausea/vomiting. However, people with bloodstream or severe joint infections may not show typical signs of infection. Thus, health care providers and the public (family, friends and others) should be aware of other symptoms, including flu-like symptoms.

History of Meningococcal Meningitis Treatment and Prevention

While it is possible that meningococcal meningitis has been affecting people for thousands of years, the disease was not formally described until 1805 by Gaspard Vieusseaux, a Swiss general practitioner. After that, the disease was called many things, including non-contagious malignant cerebral fever, Diplococcus pneumoniae, Diplococcus intracellularis meningiditis and, finally, meningococcal meningitis. In the 19th century, the prognosis of meningococcal disease was so poor that it was rivaled only by the plague and cholera.

The high fatality of N. meningiditis in the 19th century led to medical acts of desperation, including various bizarre and potentially dangerous “treatments.” Methods included, bloodletting; alcohol and opium consumption; the use of mercury, either topically or orally; sulphuric ether compresses; cerebrospinal fluid (CSF) drainage and puncturing the subarachnoid space, which surrounds the brain and spinal cord and contains spinal fluid.

Intrathecal Serum Therapy

Although diagnostic methods for meningococcal meningitis (e.g., Gram stain and culture) remained largely the same until very recently, therapeutic approaches evolved significantly between the 1890s and 1980s. The path to serum therapy was paved by researchers in the 1890s who were demonstrating its effectiveness against Clostridium tetani, Corynebacterium diphtheriae and Streptococcus pneumoniae. German physiologist Emil von Behring won a Nobel Prize in 1901 for demonstrating that infectious diseases (specifically diphtheria) could be cured by injecting humans with serum from recovered patients, and while he did not understand the concept of antigens or antibodies yet, he knew something in the blood was helping cure sick patients. This observation, along with the discovery that immunizing horses against a disease of interest, and then harvesting their serum, resulted in increased production of protective antibodies that could be used as an effective therapy against the disease of interest, paved the way for meningitis therapeutics.

In 1906, German researchers in Berlin, Wilhelm Kolle and August von Wassermann, described protection from meningococcal disease in guinea pigs using horse serum. Later, a polish clinician named Georg Jochmann took these findings even further and used serum therapy, delivered to humans via the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord (intrathecal), with similar success. Around the same time, Simon Flexner was studying anti-meningococcal serum therapy at the Rockefeller institute in the U.S. Flexner further demonstrated the success of intrathecal serum therapy in primates and began immunizing horses to produce serum that could be used to treat humans. These groundbreaking findings in the early 1900s inspired many other researchers to study serum therapy, immunize and bleed horses.

For years, intrathecal serum therapy was considered the gold standard therapy for meningococcal disease, but the process was painful and labor intensive. The process started by draining at least 30 mL of CSF from the patient, and then replacing it with serum by way of numerous injections into the spinal column, or the use of a gravity infusion system. The patient would then be put into the Trendelenburg position (the pelvis suspended above the head; patient is positioned upside down). This procedure would be repeated until the patient’s fever resolved, or gram-negative diplococci were no longer observed in the CSF. Despite hypersensitivity reactions in approximately 75% of patients, this methodology demonstrated good outcomes and was recommended until the 1940s.

Antibiotic Therapy for Bacterial Meningitis

In the early 1930s, studies by Gladwin Buttle and team, as well as Perrin Long and Eleanor Bliss, demonstrated that antibiotic treatment, specifically with sulphonamides, was more effective than serum therapy. This therapy was endorsed as the preferred treatment for over 25 years, until widespread antimicrobial resistance was documented. After the abandonment of sulfonamide treatment for meningococcal disease, the study and use of penicillin and chloramphenicol persisted until second and third-generation cephalosporins were demonstrated to be the safest and most effective antibiotic therapies.

This still holds true today. If meningitis is suspected or meningococcal disease is known to be present, health care providers will immediately administer antibiotics, sometimes even before a diagnosis is confirmed. The rapid progression of meningiococcal disease necessitates quick action, and the lifesaving potential of properly administered antibiotics supports such empirical therapy. During times of N. meningitidis outbreak, susceptibility of circulating strains must be determined and taken into account when selecting antibiotics or combination therapies to treat resistant strains. Depending on how serious the infection is, people with meningococcal disease may also need other treatments, including breathing support, medications to treat low blood pressure, surgery to remove dead tissue and wound care for parts of the body that are damaged by disseminated disease.

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