Most often, this disease develops in those people who suffer from weakened immunity. And also those patients who have a history of a neoplasm belonging to the class of malignant, people suffering from diabetes mellitus, hemoblastosis, AIDS and uremia.
Meningitis itself is an infection that affects the soft and hard membranes of the human brain. The clinical picture of this disease is demonstrated by chronic fever, increased drowsiness, frequent headaches, and weakness. We will talk about the causes and symptoms of cryptococcal meningitis in HIV-infected and healthy people below.
Common causes of this disease
In order for this disease to begin to develop in the human body, it is necessary to create optimal conditions for the pathogenic fungus. When it enters the patient’s blood, and this can happen through airborne droplets, the patient immediately becomes a source of infection for the environment. The most common pathogens and causes of cryptococcal meningitis, photos of which are not posted for ethical reasons, are:
- Cryptococci. These pathogens are the most common. They enter the environment from bird droppings, such fungi can be found in fresh fruits and vegetables, and many streptococci are stored in the soil. And you can easily become infected with this fungus while eating or inhaling dust particles. The majority of people who get sick in this way are people who have AIDS. Among them, cases of infection are much more common.
- Candida. This type of fungal disease is natural, it lives in the human body, but is in a dormant state. If it is activated, the development of infectious diseases will begin, often occurring against the background of immunodeficiency. Cases of meningitis from the Candida pathogen account for 15% of the total number of patients.
- Coccidia. For this virus to become a cause of meningitis, one must live in endemic regions of the United States or Central America.
These viral diseases primarily affect the brain. This occurs against the background of other infections, most often the disease affects elderly patients who have a deficiency of immunity, and pregnant women. Unfortunately, those at risk are those who experience immunodeficiency. Cryptococcal meningitis affects HIV-infected people, patients with diabetes mellitus, people suffering from alcoholism, newborns, and patients who have undergone cytostatic therapy. Cancer patients, patients with chronic renal failure and people who have blood diseases are also at risk.
Causes
The main reason why cryptococcal meningitis develops is a weak immune system that is unable to fight the pathogen. You can become infected anywhere; the pathogen is resistant to the external environment and can survive in open ground for a long time without losing its ability to become infected.
The damage to the central nervous system is caused by the absence of anticryptoccal factor in the medulla, in contrast to the blood serum, which does not allow bacteria to multiply in the tissues.
Mechanism of infection
When a virus enters the human body, it becomes a pathogen and protective immunological factors begin to respond to it. They have the function of preventing further development of infection, provided that the patient is physically healthy.
If a person has a weakened immune system, fungal diseases will begin to develop in the body without any problems. Against the background of this disease, immunity will begin to gradually decline, as it will try to resist fungal spores, but at the same time the blood flow will carry them throughout the body, provoking the development of cryptococcal meningitis in various organs and tissues. In these places, the active development of the pathogen will occur. The moment the spore enters the brain membrane, the fungus will have to face a real barrier, since the brain tissue provides complete protection against penetration.
Who is susceptible to cryptococcal meningitis?
The risk of infection increases in people with a reduced immune status - these are HIV-infected people and patients with AIDS disease.
Patients become infected with cryptococcal meningitis when the level of CD4 lymphocytes in the blood decreases to less than 100.
Let us remember that CD4 are white blood cells and lymphocytes. They are otherwise called immune T cells. They are responsible for immune reactions in the body. In a healthy person, their level is 450–1600, but when you get sick even with the flu, this number temporarily changes. CD4 cell counts are consistently reduced in HIV-infected patients. Therefore, their risk of contracting cryptococcal meningitis increases sharply.
How is it going?
Cryptococcal meningitis during its active formation is accompanied by serious inflammation. As the disease develops, the tissue membrane becomes clouded and thickened, and its surface becomes slightly lumpy. In rare cases, the patient experiences pathology in the form of hemorrhage. The inflammatory process is actively spreading and at any moment can begin to attack the cerebral substance, and thus encephalitis in the membrane of the spinal cord will begin to develop.
What happens when infected with a fungus?
The fungus attacks the skin and lungs. The pulmonary form of the fungus occurs without symptoms of the disease. The Cryptococcus fungus has a neurotropic effect. Its final stop is the brain and its soft membranes. The most common manifestation of cryptococcosis is meningitis. With a decrease in immunity in patients with AIDS disease and HIV-infected people, the blood-brain barrier (BBB) is disrupted, through which the fungus penetrates into the membranes of the brain. In this case, serous-productive meningitis develops with pinpoint hemorrhages in the dura and pia mater of the brain. The progression of the process is accompanied by thickening of the membranes, which are completely covered with tubercles. The process is not limited to the membranes - it extends to the base of the brain and below, into its trunk.
Risk factors for cryptococcal meningitis include: HIV and AIDS
Classification of the disease
In neurology, several definitions of this lesion are used; they are classified depending on the etiology and clinical course. Depending on the pathogen that affects the human body, meningitis can be cryptococcal and candidiasis or aspergillosis, as well as histoplasma. Depending on the course of the disease, meningitis is divided into:
- chronic;
- subacute;
- spicy.
Chronic means symptoms last for several weeks; as for clinical manifestations, this occurs at a moderate pace. If we consider the subacute variant, it differs from the acute one in that the symptoms appear slowly and are a little blurred. Subsequently, such meningitis can turn into chronic.
Acute meningitis appears suddenly, it develops quickly, and the symptoms demonstrate themselves “in all their glory.” This type of meningitis is extremely rare, and it is predominantly of the candidal type.
Cryptogenic meningitis: cause
Meningitis of this type can develop in a patient after long-term treatment with large doses of corticosteroids, antibiotics, cytostatics and immunosuppressants, after organ transplantation. Cryptogenic meningitis is a fungal infection of the meninges, most often caused by cryptococcus. Cryptococcosis affects people with a weakened immune system; infection with fungi occurs through inhalation; the pathogen can remain latent in the lungs for a long time. It is the lungs that are the primary site of localization of the pathogen.
A fungal infection is activated when the function of the immune system decreases and affects the patient’s organs and tissues. Cryptococcosis may be asymptomatic or may manifest itself with various symptoms. The most common form of the disease is cerebral cryptococcosis - the pathogen affects the central nervous system through the hematogenous route. When fungi enter the brain vessels, the walls of blood vessels are destroyed, blood microcirculation is disrupted, focal brain lesions and neuronal degeneration develop.
The permeability of brain vessels increases, which leads to the accumulation of fluid in the brain substance. Autopsy shows serous-productive meningitis with multiple small hemorrhages in the hard and soft membranes of the brain. There is an accumulation of fungi on the surface of the meninges. The pathological process often involves the basal surface, leading to the development of cerebral edema and death.
Symptoms of the disease
The onset of the disease often has characteristic indicators; they demonstrate symptoms very slowly, so it is not immediately possible to determine an accurate diagnosis. But the patient develops headaches, fever, vomiting and drowsiness.
Vomiting may be repeated, and each time you feel worse. The patient’s body temperature will remain at 37.2 and 37.9. Also, one of the symptoms of cryptococcal meningitis is that the patient loses his appetite, has a complete aversion to food, is in a lethargic state, constantly wants to sleep, fatigue occurs very quickly, reaction seems sluggish. Patients often experience sensitivity to light and anxiety.
Prevention of cryptococcal meningitis
After a course of treatment, the risk of recurrence of the disease cannot be excluded. To avoid recurrence of infection, treatment with Fluconazole orally is used at a dose of 400 mg per day for 2 months. Subsequently, the dose is reduced to 200 mg per day. The course of treatment at this dose continues until the CD4 level rises above 100. If symptoms of relapse appear, it is necessary to repeat Fluconazole.
Antifungal drug
As a result, let us clarify that cryptococcal meningitis in our time is detected mainly in patients with HIV infection with a CD4 count below 100. A mild form of cryptococcal meningitis is treated with Fluconazole according to the given scheme. For moderate disease, Amphotericin B is used, preferably liposomal called Ambisome. After a course of treatment, prophylactic use of Fluconazole is recommended to avoid recurrence of infection.
Diagnosis of meningitis
It is extremely difficult to diagnose such a disease, since the symptoms are very vague, there are no clear signs of meningeal syndrome, and this, in turn, makes it difficult to make a correct diagnosis. In order to find out what is wrong with the patient, it is necessary to conduct the following studies:
- Examination by a neurologist. The doctor will monitor the patient, find out if there are any meningeal symptoms, assess the level of consciousness, and also find out if there are signs that would indicate damage to the spinal cord.
- A lumbar puncture is performed. This procedure allows you to determine liquid pressure, also understand the degree of transparency of the cerebrospinal fluid and evaluate its color. After this, the liquid is sent for microscopy, where, in case of disease, fungal spores are found.
- MRI of the head. This procedure is performed in order to avoid cerebral expressions.
Tests are sent to the laboratory to verify the pathogen and determine its sensitivity to antimycotic drugs.
Once symptoms of cryptococcal meningitis are identified, treatment should be initiated immediately.
Crypto meningitis: treatment
Antimycotic (antifungal) drugs are used to treat cryptococcal meningitis. The action of the antimycotic drug is based on the disruption of protein formation after integration into the ribonucleic acid of the pathogen. The drug inhibits fungal DNA synthesis and thymidylate synthetase activity. Drugs with a fungistatic effect form pores in the fungal cell membrane, disrupt the cellular structure and cause the death of the pathogen. Combination antifungal therapy makes it possible to delay the development of fungal resistance to drugs.
Depending on the severity of the patient’s condition and the presence of concomitant diseases, the doctor prescribes treatment: etiotropic therapy is carried out, intracranial pressure is adjusted to avoid the development of cerebral edema. Diagnosis of cryptococcal meningitis is difficult; often this type of meningitis is diagnosed in late stages due to the absence of pronounced meningeal symptoms.
With timely treatment of cryptococcal meningitis, the development of severe complications can be avoided. The risk group for cryptococcosis includes people who have had serious illnesses, who have been taking certain groups of drugs for a long time, and those with AIDS and malignant diseases. The appearance of symptoms such as constant headache, weakness, nausea may be the first sign of the disease. At the Yusupov Hospital, neurologists, therapists and other specialists provide consultations. Treatment of severely ill patients is carried out in the intensive care unit. After illness, patients can undergo recovery in a rehabilitation center. You can make an appointment with a doctor by calling: Yusupov Hospital.
A course of treatment
Therapy should not be carried out under any circumstances without consulting a specialist. The course of treatment is determined by the doctor and has three directions:
- Monotherapy. It is carried out using a slow drip of medication to the patient. If there are indicators that require more intensive administration of the drug, then therapy may take from 1.5 to 2.5 months. This treatment lasts until the cerebrospinal fluid is completely sanitized.
- Combined treatment. This type of procedure involves a combination of several drugs intended for complex therapy. This method is considered the most effective in patients with streptococcal infection. The combination of drugs is prescribed individually; at the moment, no specific set has been established.
- Anti-relapse therapy. This measure is necessary as a preventive measure so that the disease does not recur. Just as the main treatment is carried out, the therapy for relieving symptoms is also carried out. Doctors are engaged in stopping vomiting, normalizing internal pressure, and fighting convulsive syndrome, which often occurs in patients with meningitis.
Treatment of cryptococcal meningitis
Cryptococcal meningitis in mild initial form is treated with antifungal tablets Fluconazole or Itraconazole.
To treat the disease in acute and moderate severity, the following treatment methods are used:
- As a treatment method for increased intracranial hypertension, lumbar puncture is used, which prevents brain damage.
- Administration of Amphotericin B through the central vein, the daily dose of which is 0.3–0.5 mg/kg. It is administered intravenously by drip or jet injection. To reduce the side effect of an increase in temperature to 38.0–40.0 °C, give Tylenol or Ibuprofen 30 minutes before the infusion. Amphotericin is produced (Russia) in 10 ml bottles containing 50 thousand units of lyophilisate for preparing a solution. This broad-spectrum antimicrobial drug kills fungi. Amphotericin B has a toxic effect on renal function, which recovers several months after the end of treatment. Side effects also include hypokalemia, anemia and magnesemia.
Medicine for systemic use
Modern forms of liposomal Amphotericin B, packaged in thick-walled vials, have fewer side effects. The American company Gilead Sciences Inc. produces a drug called Ambisome. Release form: bottles of 50 mg of dry substance for preparing a solution. Ambisome does not have a toxic effect on the kidneys and has few side effects, therefore it is used for renal failure.
- For patients without immunodeficiency, Amphotericin B is prescribed in combination with Flucytosine for the treatment of severe cryptococcal meningitis. The daily dose of Flucytosine is 150 mg/kg in 4 divided doses. The course of treatment is 1.5 months.
If symptoms are identified and the diagnosis of meningitis is confirmed at an early stage, the standard treatment regimen consists of Amphotericin B with oral Fluconazole capsules for 2 weeks. Moderate disease requires treatment with Amphotericin B with or without Flucytosine.
Complications
In 40 out of 100 patients, meningitis occurs with disturbances in the functioning of internal organs. This leads to nausea and frequent vomiting. This infectious process begins to develop and penetrates the membrane of the spinal cord or brain, and thus radicular syndrome appears.
If the disease has transitioned to an infectious-inflammatory level, then in this case the cerebral tissues begin to acquire new symptoms, and a serious disturbance of consciousness occurs. This fungal disease is very dangerous as it can affect the brain, leading to coma or death.
Diagnostics
To diagnose the disease, a number of measures are carried out; a visual examination of the patient is not enough:
- taking anamnesis;
- laboratory blood test for the presence of antibodies;
- fungal culture culture;
- CT or MRI of the brain.
CT or MRI of the brain for the diagnosis of cryptococcal meningitis.
The main diagnostic method remains puncture of the cerebrospinal fluid.
They take it in two ways:
- lumbar puncture;
- lumbar puncture.
This type of diagnosis is the most informative, and can confirm or refute the diagnosis 100%.
