Opportunistic infections are a large group of infectious diseases that develop in patients with various types of immunodeficiency and are uncharacteristic for people with normal immune status. Pathologies affect any organ system and cause the corresponding symptoms. Common clinical manifestations include prolonged subfebrility, lymphadenopathy, asthenic syndrome. Diagnosis of opportunistic infections includes serological, molecular genetic, bacteriological and other methods of detection of pathogenic pathogens. Treatment programs combine long-term etiotropic therapy with immunocorrection methods.
A00-B99 Some infectious and parasitic diseases
The problem of opportunistic infections (OPI) is becoming more and more urgent, which is caused by an increase in the number of HIV-infected people, the development of effective, but aggressive methods of treating cancer pathology. At the same time, many people are asymptomatic carriers of OPI pathogens: 60% are infected with cytomegalovirus, 90% with herpesviruses of types 1 and 2, about 30% with toxoplasma. Given the clinical polymorphism and the absence of specific symptoms, the diagnosis and treatment of opportunistic diseases is a serious multidisciplinary problem.
For the manifestation of opportunistic infections, infection with a pathogenic microorganism is necessary: a virus, a bacterium, a fungus or a protozoan. More than 20 typical pathogens of OPI are known, and this list is constantly being supplemented in modern infectology. The disease occurs when a latent focus is activated, less often it is a consequence of the current infection. Of paramount importance is the violation of the immune status due to the following pathologies:
- HIV infection. The most common reason, because at a certain stage of a decrease in the number of CD4 cells, OPI develop in every patient. Infectious diseases are used to diagnose HIV infection and determine the stage of the disease, so in this context they are called AIDS-associated or AIDS-indicator pathologies.
- Malignant neoplasms. The pathophysiology of any tumor process involves the suppression of the patient’s own immune system and a decrease in its response to foreign agents. At the same time, the number of T cells decreases, the processes of phagocytosis are inhibited. The problem is most pronounced in hemoblastoses – leukemias and lymphomas.
- Chronic somatic pathology. Inhibition of the activity of cellular and humoral immunity occurs in endocrine diseases (diabetes mellitus, hypothyroidism), renal insufficiency, severe inflammatory pathologies of the gastrointestinal tract.
- Iatrogenic factors. The use of cytostatics and other types of immunosuppressants is an important predictor of the development of opportunistic infections. A similar situation is observed in a group of patients after radiation therapy, organ and bone marrow transplantation.
- Primary immunodeficiency. This group includes all types of immune insufficiency that are genetic in nature or occur in utero under the influence of teratogens. They manifest themselves in early childhood, manifest themselves as protracted opportunistic diseases that are difficult to treat.
Although the causative agents of opportunistic infections are taxonomically heterogeneous, common features of their pathogenicity and virulence play an important role in the development of diseases. The properties of microorganisms that cause OPI include the possibility of long-term and even lifelong persistence in the human body, intracellular parasitism, a tendency to damage cells of the monocyte-macrophage system.
Infections are activated with immunodeficiency of any etiology and are prone to chronic course with periodic exacerbations, damage to vital organs. Opportunistic diseases are characterized by lymphogenic and hematogenic dissemination of microorganisms, the formation of ectopic foci. The patient’s own immunity is not able to provide proper resistance to the infectious agent, medicines are not always effective.
The complexity and danger of opportunistic infections also lies in the fact that they are able to suppress natural immunity. In recent years, they have been talking about the possibility of lifelong immunosuppression with the persistence of herpesviruses. Thus, a vicious circle is formed when immunodeficiency provokes the activation of OPI pathogens, which exacerbate the phenomena of immune deficiency and potentiate further multiple organ disorders.
There is no unified systematization of opportunistic infections today. Conditionally, pathogens are grouped into 3 groups: pathogens that affect people with impaired immunity and healthy people; microbes that occur only with immunodeficiency; vaccine strains of microorganisms. The classification of OPI according to the type of pathogen is generally accepted:
- Viral. Reactivation of latent pathogens against the background of immunodeficiency is typical for representatives of the herpesvirus family: cytomegalovirus, Varicella-Zoster virus, type 8 herpesvirus associated with Kaposi’s sarcoma.
- Bacterial. Opportunistic infections include infections caused by mycobacteria: tuberculosis and atypical mycobacteriosis. There are also staphylococcal infestations, bartonellosis, clostridiosis.
- Protozoal invasions. Cerebral toxoplasmosis, isosporiasis, cryptosporidiosis and microsporidiosis pose a great danger to immunocompromised patients.
- Mycoses. The most popular pathogen of this group is candida fungi, which cause up to 64% of mycoses in HIV–infected people. No less formidable is pneumocystosis. Fungal infections also include cryptococcosis, histoplasmosis.
In infectology, there is a general group of clinical signs that occurs with any variant of OPI. The most typical symptom is long-term subfebrility, which occurs for no apparent reason and worries the patient for more than 1 month. Often, an increase in temperature occurs after an acute respiratory viral infection or intestinal infection, which act as a trigger factor for the activation of an opportunistic disease.
The second alarming symptom is lymphadenopathy – an increase in lymphatic catch. Most often, the lymphoid tissue of the cervical-submandibular, axillary and inguinal zones is involved in the process. The lymph nodes reach a diameter of about 1 cm, have a dense elastic consistency, are not soldered to the surrounding tissues and are painless when felt.
The third group of general symptoms of opportunistic infections is asthenic syndrome. It includes weakness, increased fatigue, decreased tolerance of mental and physical exertion. Often patients complain of night sweats, dizziness and headaches, sleep disorders. With the long-term existence of such signs, cognitive dysfunction, emotional depression, and a persistent decrease in performance are observed.
A patient with immunosuppression should be alerted by cough and shortness of breath – typical signs of tuberculosis and pneumocystis pneumonia (PCP), decreased visual acuity – a possible manifestation of cytomegalovirus retinitis, prolonged diarrhea – a sign of cryptosporidiosis, microsporidiosis. Burning and dryness of the oral cavity in combination with erosions and white patches on the mucous membranes indicate oropharyngeal candidiasis.
Opportunistic diseases do not have a clearly defined tropism. The same type of pathogen can cause myocarditis, pleurisy, arthritis, meningitis and other nosological forms. They often mimic the symptoms of chronic somatic diseases, with which patients visit doctors of various specialties for a long time and to no avail. The exception is pneumocystosis, which mainly affects the lungs with the development of PCP.
Opportunistic infections are severe and potentially fatal diseases. Among patients with end-stage HIV infection, OPIS account for 90% of the mortality structure, the remaining 10% are due to Kaposi’s sarcoma, lymphomas and other non-infectious consequences of AIDS. Mortality in cerebral toxoplasmosis is about 33%, in cryptococcal meningitis – 20-30%, in pneumocystis pneumonia – 10-20%.
Of particular concern is the combination of several types of opportunistic diseases in one patient. Microbial associations are more characteristic of the late period and the chronic course of the underlying pathology that caused immunodeficiency. Combined infection is typical for immunocompromised patients undergoing inpatient treatment: in 40-50% of patients in the postoperative period, in 70-80% with peritonitis and pleurisy.
The spread of opportunistic infections negatively affects the reproductive health of the population. They cause many cases of miscarriage, embryopathies and fetopathies, delays in intrauterine development. Children born to mothers with OPI are at risk of developing neonatal diseases, perinatal encephalopathies.
The examination of patients is carried out by a multidisciplinary team of doctors, which includes an infectious disease specialist, an immunologist, an oncologist and other narrow-profile specialists. It is of great clinical importance to clarify the time and conditions of the appearance of symptoms, the nature of the course of the disease, the presence of risk factors for immunodeficiency states. The following diagnostic methods are used to confirm opportunistic infections:
- Instrumental visualization. Taking into account the leading clinical symptoms, chest and abdominal radiography, abdominal ultrasound, CT or MRI of the brain are performed. If necessary, bronchoscopy and colonoscopy, lumbar puncture are prescribed. If possible, invasive diagnostic methods are avoided in patients with immunosuppression.
- Serological testing. Clinically significant for the acute process or exacerbation of latent infection is an increase in antibody titers by 4 or more times in IFT. To determine the prescription of infection, especially for CMV and other herpesviruses, the avidity of antibodies is determined. ELISA is also performed for IgM antibodies.
- PCR diagnostics. The molecular genetic method remains the “gold standard” for determining most infections. Different types of biomaterial are used for its implementation. Due to the high sensitivity, PCR detects even single copies of opportunistic pathogens in the sample.
- Microbiological crops. For the cultivation of microorganisms, special culture media are used, taking into account the intended pathogen. When receiving colonies of pathogens, they are tested for sensitivity to antimicrobial drugs in order to choose the right treatment.
- Immunogram. For the diagnosis of cellular immunodeficiency, the number of different types of T-lymphocytes plays an important role, the ratio of CD4/CD8 cells is the immunoregulatory index. The humoral link of immunity is assessed by the level of CD19 (a marker of B-lymphocytes), the concentration of different classes of immunoglobulins.
In the course of treatment, practitioners of infectious diseases face such nuances as multiple drug resistance of pathogens, heterogeneity of the pathogen population, low activity of natural immune factors. The basis of therapy is the reception of etiotropic antimicrobial drugs: antibiotics, antimycotics, antiprotozoal and antiviral. Treatment of OPI has a number of features:
- mainly combinations of 2-3 drugs are prescribed to increase their effectiveness;
- the duration of antimicrobial therapy increases by 1.5-2 times or more in comparison with the treatment of infectious diseases in immunocompetent individuals;
- when selecting therapy, they focus not only on the clinical picture of the disease, but also on the current immune status of the patient;
in viral infections, etiotropic drugs are necessarily prescribed, whereas in people without immunosuppression, antiviral agents are used only according to indications.
Successful treatment of OPI requires the maximum possible restoration of immune function. In the group of patients with HIV infection, protocols of antiretroviral therapy are prescribed to increase the number of CD4 cells and improve long-term prognosis. Personal schemes of immunomodulators, experimental directions of immunotherapy and regenerative medicine with the use of stem cells are used in the management of cancer patients.
Prognosis and prevention
The course of any infection against the background of immunosuppression is complex and unpredictable, however, improved treatment protocols make it possible to achieve stable remission or even complete cure. Prognostically unfavorable factors include elderly and senile age, incorrectly selected therapy, the inability to perform immunocorrection of the underlying disease.
With immunodeficiency, primary drug prevention of opportunistic infections is indicated. Sulfonamides, macrolides‑azalides, antifungal agents are used. With a positive Mantoux test or recent contact with a tuberculosis patient, chemoprophylaxis is prescribed for a period of 6 months. Also, patients are recommended to strictly observe anti-epidemic measures, in the period of severe immunosuppression, it is necessary to stay in sterile boxes.