Influenza: Diagnosis, Treatment, Prevention - V.D. Moskalyuk 2010

General information about influenza and other ARVI
Etiological heterogeneity of acute respiratory diseases

Against the Background of acute respiratory diseases (ARD), respiratory tract infections are commonly caused by various predominantly coccal microflora, legionellae, Mycoplasmas, chlamydiae, and rickettsiae (C. Rubin et al., 1997; R.I. Khaitov et al., 2000). They trigger the onset of nasopharyngitis, acute tonsillitis, and Bronchitis. Pathogens of these groups are more likely than Viruses to lead to The Development of Pneumonia (O.M. Litvinova et al., 1995; M.C. Ruzek et al., 1997; V.D. Moskaliuk et al., 2004).

Respiratory infections affect all age groups of the population (A. Nakane et al., 1981; M.A. Andreichyn, 1996; T.P. Salazar et al., 2002). To date, a significant number of viruses (over 250 types) belonging to 9 different viral nosological groups are known (Influenza, parainfluenza, adenovirus, respiratory syncytial, picornavirus, coronavirus, reovirus, enterovirus, and herpesvirus infections). These are closely associated with human respiratory tract diseases and cause the development of acute respiratory viral infections (ARVI) (A.N. Slepushkin et al., 2001; I. Pestun et al., 2002). Viruses worsen the course of chronic bacterial respiratory infections (L.A. Luchikhin, 2002; O.V. Demikhovska et al., 2004; S.D. Zhogolev et al., 2006).

In adults, ARVI are most frequently caused by the following viruses: Influenza Viruses (3 types, including multiple type A serotypes), Adenoviruses (7 subgroups, each containing 1 to 19 serotypes), respiratory syncytial virus, parainfluenza viruses (5 serotypes), rhinoviruses (113 human serotypes and 2 bovine serotypes), Coronaviruses (4 groups with numerous serotypes), ECHO and Coxsackie enteroviruses (up to 70 serotypes), Herpesviruses (8 types, some with various serotypes), and reoviruses (K.D. Ryman et al., 2000; N.S. Zhuravska et al., 2002).

This list excludes diseases accompanied by a respiratory syndrome but characterized by specific clinical manifestations (such as rash in measles or chickenpox, and generalized lymphadenopathy in infectious mononucleosis). It refers exclusively to conditions with remarkably similar clinical presentations, which in many cases significantly impedes clinical Differential Diagnosis (V.V. Berezhnoi et al., 2003).

Non-viral ARD in adults are most commonly caused by the following microorganisms: opportunistic coccal microflora (acute pharyngitis, bronchitis, tonsillitis); legionellae; mycoplasmas; and rickettsiae.

According to Zh.I. Vozianova (2002), the diagnoses of ARVI, and even more so ARD, are highly vague. At the same time, such formulations are overly convenient as they allow clinicians to avoid specific diagnosis while appearing "up to date." Even mildly expressed respiratory symptoms (which, as noted earlier, are not always of infectious origin) are deemed sufficient to label the condition as "ARD." It is not without reason that these groups of infections are referred to as "mass graves"—they conceal medical errors stemming from ignorance, carelessness, or levity, which are utterly unacceptable in the medical profession.

Scientific publications very often feature the phrase "influenza and ARVI." As previously mentioned, this is an incorrect and even harmful formulation because it fails to provide the slightest understanding of the true relationship between influenza and other acute respiratory viral infections (given that influenza is also an ARVI, albeit one for which routine specific prophylaxis is available) (Zh.I. Vozianova, A.M. Pechinka, 2002).

When etiological confirmation of respiratory pathology is impossible, it is more logical to use the formulation "influenza and other ARVI," though very cautiously. In cases of ARVI, an individual with clinical symptoms always becomes a source of infection. Pathogen shedding begins already during the incubation period, but the greatest danger arises precisely during the acute phase. The duration of virus shedding can range from 1–2 months or even longer (J.S. Jong et al., 1998; K.I. Grigoriev, A.M. Zaprudnov, 2002).

The airborne transmission route of the pathogen and high population susceptibility to virtually all ARVI-causing viruses determine their primary epidemiological feature—the speed and breadth of their spread (A.O. Rudenko, 1999).

The potential for airborne dissemination, as well as the mass infection of people indoors, is practically unlimited. These rates increase significantly during epidemic outbreaks of ARVI, particularly under conditions of high population density, which is especially typical of the autumn-winter and winter-spring periods. Repeated episodes of ARVI, even during seasonal spikes in morbidity, are caused by the lack of cross-Immunity not only between different virus groups but also among individual serotypes within the same species of pathogen. Furthermore, It is important to note that these pathogens are quite stable in the environment, surviving from 1–8 hours up to 7 days or longer (Zh.I. Vozianova, A.M. Pechinka, 2002).

Many ARVI-associated viruses are characterized by chronic carriage—persistence; however, its significance (aside from adenoviruses) in spreading infection has not been proven. Nevertheless, viral persistence and latency, combined with a vast array of serotypes, make their eradication practically impossible (S.O. Pestka, J.A. Langer, K.C. Zoon, C.E. Samuel, 1987; R. Nerome, Y. Hiromoto, S. Sugita et al., 1998).

In addition to the droplet transmission mechanism, other routes of spread are possible for certain ARVI. A fecal-oral mechanism can occur in adenoviral infections, while contact transmission is characteristic of respiratory syncytial virus (RSV) infection. Unusual transmission routes—via various transplants—have also been identified. This latter route has proven particularly significant for the herpesvirus group (Yu.V. Lobzin, N.I. Lvov, 2001).

ARVI is characterized by 2 forms of the epidemic process: sporadic cases and epidemic outbreaks. In addition, certain types of ARVI tend to acquire a nosocomial infection pattern. This primarily applies to RSV infection. According to some data, up to 20–40% of infants hospitalized for other reasons contract nosocomial RSV infection in the hospital Setting. These outbreaks are distinguished by high contagiousness (A.P. Alexenko, D.W. Leaman, R.M. Roberts, 1997; I.V. Loskutova, I.O. Shapovalova, V.O. Tereshyn, Y.A. Sotska, 2002).

Most ARVI types are characterized by seasonality, with peak incidence rates recorded in autumn and winter, whereas enteroviral infection peaks in spring and summer. However, isolated outbreaks—such as parainfluenza or adenoviral infection—may occur during the summer months. These outbreaks can trigger the activation of both epidemic and latent strains due to a decrease in human immune defenses influenced by external or internal factors (excessive solar radiation, physical exhaustion). In such cases, the infectious process in ARVI often takes a subclinical or inapparent course rather than a clinically overt one, where disease symptoms are absent, yet a fourfold or greater increase in pathogen-specific antibody titers is detected in Blood serum. Inapparent forms are most frequently recorded in adults, accounting for up to 55–73% of infection cases (E.M. Bennett, J.R. Bennink, J.W. Yewdell et al., 1999).

The epidemic process of ARVI is influenced by biological, social, and environmental factors, which remain insufficiently studied to date. Landscape, biocenotic, climatic, and other conditions either promote or hinder the persistence of ARVI pathogens. For instance, adenoviral infection occurs more frequently in northern regions and less frequently in the south. No such pattern has been established for parainfluenza (A.M. Naykhin, S.A. Artemyeva, L.V. Bosak, L.G. Katorgina, 1995; R. Pyhll, N. Ikonen, T. Forsten et al., 1995).

Given the high contagiousness of ARVI, clinical differential diagnosis is critically important, as it should guide the Isolation of the most contagious patients adhering to specific isolation periods and ensure the proper placement of patients within the hospital. These measures are pivotal in halting the spread of the infection (F.I. Ershov, S.S. Grigoryan, T.A. Semenenko et al., 1991; M.V. Pashenkov, B.V. Pinegin, 2002).

While clinical differential diagnosis among viral respiratory infections has little impact on the Treatment regimen (which is predominantly pathogenetic), distinguishing bacterial and other non-viral infections from viral ones is of substantial importance: they require not only active etiological treatment, but in some cases specific serotherapy as well (F.I. Ershov, E.P. Tazulakhova, 1999; F.I. Ershov, 2003).

According to Zh.I. Vozianova, all ARVI types are characterized by:

1. Complaints of varying degrees of general intoxication symptoms, catarrhal symptoms (throat tickling), and much less frequently — sore throat, rhinitis, and dry cough. These symptoms indicate involvement of the upper respiratory mucosa at all levels. Each specific type typically causes the most severe damage to one or two sections of the Upper Respiratory Tract. Consequently, each viral infection exhibits its own target lesion zone and distinct clinical symptoms.

2. In the vast majority of cases, viral infections are characterized by symptoms of catarrhal inflammation: moderate hyperemia, primarily of the fauces, soft palate, uvula, and posterior pharyngeal wall, accompanied by granularity (enlarged lymphoid follicles — Morozkin's sign), hyperemia of the nasal passage mucosa, and to a lesser extent, the Tonsils. Only rarely do ARVI cases feature productive changes on the tonsils; pus in the tonsillar lacunae can be detected in adenoviral infection and characteristically in infectious mononucleosis, yet even in these instances, such changes are predominantly driven by mixed pathology (a combination with bacterial tonsillar involvement). Unfortunately, our knowledge regarding such coinfections in other illnesses remains very scarce. Sputum is invariably serous or seromucous. The appearance of pus is a sign of a secondary bacterial complication.

3. Many viral infections are characterized by the development of Conjunctivitis and episcleritis, the severity of which depends on the specific disease and its gravity, with discharges also being serous rather than purulent.

4. In a complete blood count, ARVI typically manifests as leukopenia or normocytosis with a band neutrophil shift, lympho-monocytosis, and a normal ESR level. Mild leukocytosis may occur solely in adenoviral infection, though accompanied by the same blood formula changes (A.M. Naykhin, S.A. Artemyeva, L.V. Bosak, L.G. Katorgina, 1995; O.A. Melnikov, L.V. Averkieva, 2004).

5. Radiologically, ARVI cases uncomplicated by pneumonia or acute respiratory distress syndrome frequently reveal enhanced pulmonary vascular markings.

Acute respiratory diseases caused by Legionella, Mycoplasma, and Chlamydia occupy an intermediate position between ARVI and coccal-Etiology acute respiratory illnesses in terms of their clinical manifestations and laboratory profile (Zh.I. Vozianova, A.M. Pechinka, 2003).

The distinctive features of these acute respiratory diseases include: they most commonly occur during the non-epidemic period of the year (summer and autumn); the onset varies from acute to gradual, but catarrhal symptoms appear from the very first day of illness; upper respiratory tract involvement is accompanied by serous or seromucous discharge; relative bradycardia is possible; conjunctivitis and episcleritis occur rarely; blood tests show neutrophilic leukocytosis of varying severity and an elevated ESR; progression to pneumonia or relapse is possible.

Significant difficulties arise when conducting the clinical Cytology/practical/136.html">DIFFERENTIAL DIAGNOSIS OF acute respiratory viral infections (ARVI) (Zh.I. Vozianova, V.I. Piven, I.V. Shestakova et al., 2004). This is due to the fact that diseases with different etiological factors share very similar clinical symptoms. Having precise knowledge of the ARVI pattern within a country and in specific foci is one of the most critical conditions for successfully developing and implementing new Methods for combating and preventing these infections. Based on the speed of obtaining results, these methods are divided into rapid assays (duration less than 1 hour), medium-duration methods (more than 1 hour, less than a day), and standard diagnostic methods, which take several days to complete (V.A. Isakov, 2002).

Rapid diagnostic methods for ARVI make it possible to prescribe targeted etiotropic therapy to patients in a timely manner, which is most effective During the first 2 days of the illness (V.D. Moskalyuk, 2004).

In addition to rapid diagnostic assays, medium-duration diagnostic methods are also employed (Zh.I. Vozianova, A.M. Pechinka, 2003).

1. Enzyme-linked immunosorbent assay (ELISA): detects IgM and IgG Antibodies. This is the most promising and accurate approach.

2. Indirect hemadsorption test.

3. Polymerase Chain Reaction.

Focusing on medium-duration methods, which are among the most advanced, it should be noted that the polymerase chain reaction can be effectively utilized only in its quantitative format. This is due to the potential simultaneous presence of multiple viruses on mucous membranes and the extremely high sensitivity of the reaction (Zh.I. Vozianova, A.M. Pechinka, 2003). Standard diagnostic methods include:

1. Virological examination (using chicken embryos, laboratory animals, Cell cultures, and neutralization tests).

2. Analysis of the rise in specific antibody titers in paired serum samples collected dynamically (with an interval of 10-14 days between samples) — utilizing indirect hemagglutination inhibition, hemagglutination inhibition, Complement fixation tests, etc.

3. Fluoroimmunoassay using Monoclonal Antibodies.

4. Nucleic acid molecular Hybridization method.

Standard diagnostic methods are accurate yet time-consuming, and therefore they are most commonly applied in scientific research. Serological Methods for determining dynamic antibody titers can be used in clinical practice; however, establishing an etiotropic diagnosis this way will not alter the course of treatment, but rather serves to identify the Circulation of specific viruses (Zh.I. Vozianova, A.M. Pechinka, 2003).

Laboratory Diagnostics for such acute respiratory infections are predominantly serological. Most frequently, enzyme immunoassay is used to detect specific IgM and IgG, along with the indirect immunofluorescence assay (for legionellosis), the dynamic complement fixation test, and polymerase chain reaction. All of these require specialized equipment and expensive Reagents, meaning not every medical institution can afford such testing. Conventional (classical) bacteriological diagnostics are rarely used due to the technical complexities of the method, The Need for specialized culture media, and its low efficacy (E.N. Gorban, N.D. Tronko, I.P. Pasteur et al., 1996).