Brain Fever: Meningitis Symptoms, Diagnosis, Treatment, and Prevention

Early mentions of meningitis date back to the 17th and 18th centuries. Several writers mentioned brain fever, referring to people with headaches, fevers, and delirium – some common symptoms of meningitis. In 1803, François Herpin, a French military surgeon, was the first to write a dissertation on the illness, referring to it as an inflammation of the brain’s membranes [10]. 

In 1805, Gaspard Vieusseux, a physician based in Geneva, Switzerland, developed the first and most comprehensive clinical description of the illness. Vieusseux described the disease further during the epidemics that occurred in the subsequent years in New England, Canada, Virginia, Kentucky, Ohio, and Pennsylvania states in the USA between 1806 to 1809 [11].  

In 1887, Anton Weichselbaum, an Austrian pathologist and bacteriologist, identified the causative agent of the illness in New England. The first epidemics of meningitis occurred in Sub-Saharan Africa [12]. It continued to spread to countries in Europe, the Americas, and Asia throughout the 19th century, with case fatality ranging from 69% to 100%.

In 1905, Simon Flexner, an American scientist from the New York Rockefeller Institute for Medical Research, New York, USA, conducted experiments by immunizing horses to validate the effectiveness of the anti-meningococcal serum intended for treating humans. The serum was therapeutically effective, and clinicians began recommending it as a preventive medicine for people in close contact with patients with meningococcal disease.  

In 1937, Francis Schwentker and colleagues used sulfonamides to treat patients with meningococcal disease. The results were positive, with all ten patients surviving the illness. Extensive studies were done on the effectiveness of sulfonamides in treating meningitis in the subsequent years.

A few years later, in 1944, David Rosenberg and Phillip Arling used penicillin to treat patients with meningitis, and the outcome was positive. In 1968, the emergence of an epidemic caused by a sulfonamide-resistant strain, N. meningitidis, in Brazil made clinicians switch from sulfonamides to penicillin. Penicillin became a drug of choice for many years [11].   

But, the breakthrough came with the development of the first Haemophilus influenza type B conjugate vaccine (HiBCV) in 1985. In 1999, the first meningococcal conjugate vaccine was approved for public use in the UK. 

In 2000, the heptavalent pneumococcal conjugate vaccine (PCV7) was licensed [13]. It was developed to protect against the seven most invasive and prevalent disease serotypes in Europe and the US [14]. In 2005, a meningococcal conjugate vaccine covering serogroups A, C, W, and Y was licensed in the US [15].

Bacterial meningitis cases and rates per 100,000 in the African region. Copyright © 1994 – 2023 GIDEON Informatics, Inc. All Rights Reserved.

Geographic distribution

Meningitis occurs worldwide. A part of Sub-Saharan Africa, extending from Senegal to Ethiopia, including Ghana, also called the extended African Meningitis Belt (AMB), is one of the most affected regions on the planet [1,16]. 

Between 1995 and 2014, a record number of 900,000 cases were reported in the region. One in ten people with meningitis died, and one in five suffered from severe neurological complications [17].

Who is at risk?

People of all age groups can be affected by meningitis. Children, especially newborns, are at a higher risk of bacterial meningitis. Other people who are at a higher risk of acquiring various types of meningitis include those who participate in mass gatherings, stay in refugee camps, and live in overcrowded houses, hostels, military, and other occupational settings.

Also, people with a weak immune system, including HIV infections, cancer, and other immuno-suppresive illnesses, are vulnerable to acquiring different types of meningitis. The list also includes active and passive smokers [1].

Outbreaks

Meningitis continues to remain a global health concern despite all the recent advancements in the development of vaccines. Over 5 million cases and around 300,000 deaths due to meningitis occur worldwide each year. Over 50% of these deaths are among children under five [14]. 

A majority of these cases are caused by bacteria. Bacterial meningitis is fatal and can result in death within a few hours without timely treatment [5]. The bacteria that cause bacterial meningitis are geographically dispersed, making it a worldwide concern. Over 2.5 million cases of bacterial meningitis occur globally each year [16]. 

Meningococcal meningitis caused by the N. meningitidis bacteria accounts for around 1.2 million cases and 135,000 annual deaths. However, while the case-fatality rate was an incredibly high 70-85% during the pre-antibiotic era, it has dropped significantly to 10-20% as of 2019 [21].

The Americas

Brazil is one of the most affected regions in the Americas. Between 2009 and 2018, the country reported about 52,926 confirmed cases: 

• 19.9% were pneumococcal meningitis
• 14.8% were meningococcal meningitis 

Studies show that males (including children) were primarily affected by bacterial meningitis. 

In the United States

• Between 2006 and 2015: about 7,924 cases of meningococcal disease were reported, with an average annual incidence rate of 0.26 cases per 100,000 population. Around 14.9% of these cases resulted in fatal outcomes [19]
• In 2018, the incidence came down to 0.10 per 100,000 population, with 329 reported cases [20]

African Meningitis Belt (AMB)

• Between 2011 and 2017, 17 outbreaks of meningococcal meningitis occurred in eight African countries in the AMB. There were an estimated 31,786 suspected cases in total. Nigeria was the most affected country, witnessing five outbreaks with around 17,375 suspected cases. Niger and Burkina Faso recorded 9,343 and 2,372 suspected cases, respectively [22]
• Between 2010 and 2018, 5,590 out of 21,142 suspected cases were confirmed to be meningitis. Around 85% of these cases were caused by N. meningitidis, S. pneumoniae, caused 13%, and the remaining 2% were caused by H. influenzae [23] 
• In Ghana, about 1,176 cases of bacterial meningitis, caused mainly by S. pneumoniae, N. meningitidis, and Hib, were recorded in the Upper West Region between 2018 and 2020. There were 118 deaths and 1,058 survivors. The disease incidence during those three years (2018-2020) was 52, 41, and 48 per 100,000 population, respectively [17] 
• Burkina Faso (in the AMB region) had been hit by several meningitis epidemics over the years:
  • Notable outbreaks occurred in 1957, 1985, 1994, 1995, 1996, 1997, 2004, 2005, 2006, 2007, 2008 and 2009 
  • In 1996, the country had its biggest meningitis epidemic with over 4300 recorded deaths 
  • There were several epidemics in 1992, 2001, 2002, 2003, and 2012 as well
  • Burkina Faso is the only African nation where all residents are monitored for suspected bacterial meningitis and with vigorous testing and vaccination drives. Together with the US CDC, the country is actively working to increase its vaccination rates
  • In 2022, a bacterial meningitis outbreak in Burkina Faso, one of the countries that fall in the AMB, resulted in 1,564 confirmed cases, including 78 deaths. S. pneumoniae was found to be the leading cause contributing to around 66% of cases, followed by N. meningitidis [24] 

Bacterial meningitis

• Meningitis infections caused by H. influenzae, M. tuberculosis, and S. pneumoniae can spread when an infected person coughs or sneezes – people who are in close contact can get infected when they inhale the contaminated air
• Bacterial meningitis caused by Group B Streptococcus and E. coli can spread from mothers to their newborns during birth
• Cases caused by N. meningitidis can spread through direct contact with saliva. This happens when a person is close to an infected person who is coughing, kissing an infected person, or living with an infected person
• E. coli-inflicted meningitis is caused through contact with contaminated surfaces or food (if the food is handled with contaminated hands) [5]

Viral meningitis

Viral meningitis can be caused by different viruses, including the mumps virus, measles virus, influenza virus, nile virus, non-polio enteroviruses, lymphocytic choriomeningitis virus (LCV), and herpes viruses, including epstein-Barr virus, herpes simplex, and varicella-zoster. 

These viruses can spread in different ways and only a small percentage of people infected with these viruses will develop viral meningitis [9].  

Fungal meningitis

Fungal meningitis does not spread from one person to another. People get infected when they inhale fungal spores found in:

• Soil that contains large amounts of bird or bat droppings
• Moist soil
• Decaying wood and leaves [6]

Parasitic meningitis

Parasitic meningitis does not usually spread from one person to another. People get infected when they:

• Eat meat contaminated with parasites – raw or undercooked snails or freshwater fish or eels, frogs, poultry, snakes, slugs or other contaminated meat. 
• Eat food contaminated with parasite eggs, which are highly infectious. These are mostly found in raccoon feces [7]. 

Amebic meningitis

Amebic meningitis is caused by Naegleria fowleri. It does not spread from one person to another. People get infected when they drink water contaminated with N. fowleri [8].

Non-infectious meningitis

As the name indicates, non-infectious meningitis is not contagious. The following can cause non-infectious meningitis:

• Cancer
• Lupus
• The use of certain medications
• Head injury
• Brain surgery [4]

When a person gets infected by meningitis-causing bacteria, it usually enters the body through respiratory droplets in the air. Once it enters, the bacteria multiply in the nasopharynx and enter the bloodstream. Through the blood, the pathogen travels to the brain. Once it reaches the subarachnoid space – an area in the meninges between the arachnoid membrane and the pia mater, it crosses the blood-brain barrier, resulting in an inflammatory and immune-mediated reaction.

Infecting bacteria can also enter the cerebrospinal fluid (CSF) through inflammatory diseases of the middle ear, inflammation of the mucous membranes, or through foreign objects introduced during specific medical procedures. 

Viruses can also enter the central nervous system (CNS) through the nose, which involves reaching the subarachnoid space through the bloodstream or retrograde transmission along neuronal pathways [25].  

Bacterial meningitis

The incubation period of bacterial meningitis is between three and seven days. The symptoms include:

• Fever
• Headache
• Stiffness in the neck region
• Vomiting
• Nausea
• Confusion

The following markers could indicate the presence of bacterial meningitis in newborn babies:

• Inactiveness
• Irritability
• Vomiting
• Fontanelle bulge
• Abnormal reflexes

In the absence of immediate medical attention, people can enter into a coma and even die [5].

Viral meningitis

The symptoms of viral meningitis in children and adults include:

• Fever
• Headache
• Stiffness in the neck region
• Increased sensitivity to light
• Trouble sleeping or waking up from sleep.
• Tiredness
• Irritability
• Lack of appetite
• Vomiting
• Nausea

The following markers could indicate the presence of illness in babies:

• Fever
• Irritability
• Trouble sleeping or waking up from sleep
• Lack of energy
• Poor eating

Unlike bacterial meningitis, viral meningitis is less severe and people get better on their own in seven to 10 days [9].

Fungal meningitis

The symptoms of fungal meningitis include:

• Fever
• Headache
• Stiffness in the neck region
• Nausea
• Vomiting
• Increased sensitivity to light
• Confusion [6]

Parasitic meningitis

The following are the signs and symptoms of parasitic meningitis:

• Headache
• Stiffness in the neck region
• Vomiting
• Nausea
• Sensitivity to light
• Confusion
• Tingling or painful sensation in the skin – if the causative agent is A. cantonensis
• Low-grade fever – if the causative agent is A. cantonensis 

Baylisascaris-inflicted parasitic meningitis can cause severe illness and usually results in:

• Loss of coordination
• Loss of muscle control
• Weakness or paralysis
• Coma
• Permanent disability
• Death [7]

Amebic meningitis

The incubation period of amebic meningitis is one to 12 days. The symptoms begin with:

• Headache
• Fever
• Vomiting
• Nausea

These symptoms will be followed by:

• Stiffness in the neck region
• Lack of focus or attention
• Confusion
• Seizures
• Hallucinations
• Coma

Amebic meningitis, though rare, is more fatal. The disease is rapidly progressive, leading to death within five days on average (range is usually between one and 18 days) [8].

Non-infectious meningitis

Signs and symptoms of non-infectious meningitis include:

• Fever
• Headache
• Stiffness in the neck region
• Nausea
• Vomiting
• Sensitivity to light
• Confusion [4]

There are different ways to diagnose meningitis. Diagnosis depends on the causative agent suspected. 

• Bacterial meningitis – Blood samples or CSF are collected to detect the presence of bacteria, usually through rapid diagnostic tests or by Polymerase Chain Reaction (PCR) [5]
• Viral meningitis – Oral and nasal swabs, stool, blood, and CSF samples are usually collected and examined to detect the virus [9]
• Fungal meningitis – The fungal infection is examined in blood and CSF samples. The diagnostic methods may vary depending on the type of fungus suspected [6].
• Parasitic meningitis – Parasitic meningitis is confirmed by examining the blood or CSF samples of the patient. But, unlike other pathogens, tracing out parasites in CSF is quite challenging. So, other parameters, including travel or exposure history, clinical examination, and other medical examinations such as brain scans, are performed to make an appropriate diagnosis [7] 
• Amebic meningitis – Amebic meningitis is rare and diagnosed using laboratory tests available in the US [8]

Meningitis cases can turn out to be fatal within 24 hours, so immediate medical attention is required [1].

Treatment varies and depends on the type of pathogen causing the illness. 

• Bacterial meningitis – Antibiotics are standard therapy if the source of infection is bacteria [1,5]
• Viral meningitis – There is no specific treatment to cure viral meningitis. If the causative agents are herpesvirus and influenza, there are antiviral drugs to help people recover. No treatment is required in mild cases, as people recover within seven to 10 days [9]
• Fungal meningitis – The treatment duration is usually extended for patients with fungal meningitis  and depends on the type of fungus causing the infection. Prolonged courses of high-dose antifungal medications are administered by doctors – usually through IV and sometimes orally. People with weak immune systems, including those with AIDS or cancer, may take longer to recover [6]
• Parasitic meningitis – There is no treatment to cure meningitis caused by parasites. Supportive care is given to ease the symptoms. For instance, medications are given for headaches [7]
• Amebic meningitis – Amebic meningitis is treated with a combination of medications, including amphotericin B, azithromycin, fluconazole, rifampin, miltefosine, and dexamethasone. However, no clinical evidence attests to their effectiveness, as almost all such infections have been fatal [8]

Bacterial meningitis

There are vaccines available to protect against certain bacteria that cause bacterial meningitis. Meningococcal, Pneumococcal, Haemophilus, and Bacilli Calmette-guérin vaccines are used to protect against N. meningitidis, S. pneumonia, Haemophilus influenzae type b (Hib), and tuberculosis, respectively.

But, vaccines against meningitis infections are not 100% effective, and there are no vaccines for all other types of bacteria that cause bacterial meningitis. So, even if people get vaccinated with available vaccines, they are still vulnerable to being infected by different strains of bacteria that have no vaccines to protect against them. With this being said, vaccination is the most effective way to help protect against the most common bacterial infections causing meningitis.

In the United States, there are two types of meningococcal vaccines available: 

• Meningococcal conjugate or MenACWY vaccines (Menactra®, Menveo®, and MenQuadfi®)
• Serogroup B meningococcal or MenB vaccines (Bexsero®and Trumenba®) [20]

Here are other precautions that can help protect against bacterial meningitis: 

• Preventive treatment is given by doctors to those who got in close contact with people with bacterial meningitis caused by N. meningitidis, people with a severe Hib infection, and healthcare workers who treat patients with the illness
• Pregnant women should get tested for group B Streptococcus and take antibiotics prescribed by the doctor to prevent the infection from passing to their newborns
• Adapting a healthy lifestyle, including getting good rest, avoiding cigarettes and cigarette smoke and people who are sick, washing hands with soap and water, and covering noses and mouths while sneezing or coughing [5]

Viral meningitis

Currently, there are no vaccines available to protect against non-polio enteroviruses. But, there are vaccines to protect against other causative agents, including measles, mumps, chickenpox, and influenza. So, taking up these vaccines can help. 

Other preventive measures to help control the spread of infection include:

• Washing hands properly after using the toilet or changing diapers
• Avoid direct contact with sick people
• Make it a practice to clean and disinfect surfaces regularly
• Self-isolation while being sick [9]

Fungal meningitis

No specific practices or activities are known to cause fungal meningitis. Since people with a weak immune system have more chances of developing severe complications due to the infection, they can consider the following measures:

• Avoid construction or excavation sites, as these places are usually dusty
• Use N95 masks, or equivalent, while staying or passing by dusty areas
• Close all doors and windows during dust storms
• Avoid all of those activities that involve close contact with dust
• Clean all skin injuries properly with soap, as the wound might be exposed to dust
• Taking anti-fungal medications as per the advice of the physician [6]

Parasitic meningitis

The following preventive measure can help control the spread of parasitic meningitis. 

• Avoid eating raw or undercooked meat and vegetables that could be potentially contaminated
• Washing utensils and knives properly after washing snails and slugs
• Ensure that rats, snails, and slugs, potential parasite carriers, are removed [26]  
• Please keep away from raccoons and avoid direct contact with their feces
• Make it a practice to wash hands after working or playing outdoors
• Avoid feeding, keeping, or even adopting wild animals, especially raccoons, as pets 
• Ensure that sandboxes are covered, as raccoons might use them as toilets
• Immediately remove and clean raccoon feces. Please take all necessary cleaning precautions, including wearing N95 masks or their equivalent, gloves, and rubber boots Also, avoid stirring up dust and debris
• Make it a practice to keep the containers in and around the house closed, avoid having fish ponds, remove feeders placed for birds, and close access to food, water, attics, and basements. It will help reduce raccoon infestation [27]

Amebic meningitis

The following are some preventive measures to control the spread of amebic meningitis.

• Avoid swimming or diving into freshwater bodies during summer or when warm
• If you are swimming or in warm freshwater bodies, make it a practice to use nose clips to prevent the water from entering the nose
• Avoid stirring up or digging the sediments in shallow fresh warm water bodies. The amebae that cause meningitis mostly live in sediments of these water bodies [28]
• Use boiled, sterile, or filtered water for nasal rinsing. Chlorine can also be used to disinfect the water before use [29]

With millions of meningitis cases being reported, even today, what’s the next step towards eliminating this infection? Well, WHO is taking significant steps towards achieving this goal. 

In November 2020, the World Health Assembly approved a global road map put together by global experts and WHO with a vision for 2030 – “Towards a world free of meningitis.” The goals for this initiative are: 

• Eliminating bacterial meningitis epidemics
• Lowering case counts of vaccine-preventable bacterial meningitis by 50% and deaths by 70%
• Reducing disability and improving quality of life after all meningitis infections [30]

Hopefully, with this type of concerted focus, and early and comprehensive data on meningitis outbreaks, the world can be rid of this devastating illness in the years to come.

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Learn more about bacterial meningitis,  viral meningitis, Baylisascariasis, and meningitis caused by amoeba on the GIDEON platform.