Urgent states in patients with infectious diseases with fecal-oral mechanism of transmission. General description of group of infectious diseases with the droplet mechanism of transmission. Influenza (flu). Other ARVI (acute respiratory viral infections): parainfluenza, adenoviral disease, respiratory-syncytial infection, rhinoviral infection. Infectious diseases which run across with the clinic of atypical pneumonia: respiratory mycoplasmosis, ornithosis (psittacosis parrot fever), legionellosis (legionnaires’ disease).

Influenza (flu). Other ARVI (acute respiratory viral infections): parainfluenza, adenoviral disease, respiratory–syncytial infection, rhinoviral infection.

Definition

Influenza is acute infectious disease which occurs in epidemics and is caused by a virus, it is characterized by an abrupt onset and such manifestations as general intoxication and  affection of the respiratory tract mucosa.

http://www.cdc.gov/flu/other_flu.htm

Together with the diseases of the cardiovascular system and tumors, influenza takes the leading position in the human pathology. Influenza and other acute respiratory diseases constitute about 75% of all infectious diseases, and 85 – 90% in epidemics, thus resulting in great social and economic damage. Thus, in Ukraine in the epidemic period 1968 – 1972 the economic damage equaled about $120 million. The main thing is that besides relatively mild cases of the disease, there are severe cases resulting in disability and sometimes death when children or old people contract a disease. According to the USA statistics influenza takes the tenth position concerning fatal outcomes.

http://virus.stanford.edu/uda/

History

The first pandemic which spread from Asia to Europe and America was registered in 1580. There have been 23 great epidemics and pandemics since that time. During the pandemic of 1780 – 1782 the modern term «flu» or «influenza» appeared (from the French word «Gripper» meaning catch, envelope, Latin «influere», Italian «influenza» meaning penetrate, invade, instill).

In the manuscripts of the 14 – 15^th centuries eight epidemics are mentioned, their names are “mass epidemic”, “fatal infection”, “catarrhal fever”, “infectious fever”, “quick catarrh”, etc. Even the names show the essence of the disease. In spite of it, the authenticity of the information is not absolute.

It is impossible to determine the regularity of epidemics in the past. In some cases they were of local character affecting the population of few countries. In other cases influenza spread pandemically and affected the population of several continents.

Details of the patient’s history aid in differentiating a common cold from conditions that require targeted therapy, such as group A streptococcal pharyngitis, bacterial sinusitis, and lower respiratory tract infections. The table below contrasts symptoms of URI with symptoms of allergy and seasonal influenza (adapted from the National Institute of Allergy and Infectious Diseases).

Table. Symptoms of Allergies, URIs, and Influenza

Symptom	Allergy	URI	Influenza
Itchy, watery eyes	common	rare; conjunctivitis may occur with adenovirus	soreness behind eyes, sometimes conjunctivitis
Nasal discharge	common	common	common
Nasal congestion	common	common	sometimes
Sneezing	very common	very common	sometimes
Sore throat	sometimes (postnasal drip)	very common	sometimes
Cough	sometimes	common, mild to moderate, hacking cough	common, dry cough, can be severe
Headache	uncommon	rare	common
Fever	never	rare in adults, possible in children	very common, 100-102°F or higher (in young children), lasting 3-4 days; may have chills
Malaise	sometimes	sometimes	very common
Fatigue, weakness	sometimes	sometimes	very common, can last for weeks, extreme exhaustion early in course
Myalgias	never	slight	very common, often severe
Duration	weeks	3-14 days	7 days, followed by additional days of cough and fatigue

Viral nasopharyngitis

Symptoms of the common cold usually begin 2-3 days after inoculation. Viral URIs typically last 6.6 days in children aged 1-2 years in home care and 8.9 days for children older than 1 year in daycare. Cold symptoms in adults can last from 3-14 days, yet most people recover or have symptomatic improvement within a week. If symptoms last longer than 2 weeks, consider alternative diagnoses, such as allergy, sinusitis, or pneumonia.

• Nasal symptoms: Rhinorrhea, congestion or obstruction of nasal breathing, and sneezing are common early in the course. Clinically significant rhinorrhea is more characteristic of a viral infection rather than a bacterial infection. In viral URI, secretions often evolve from clear to opaque white to green to yellow within 2-3 days of symptom onset. Thus, color and opacity do not reliably distinguish viral from bacterial illness.
• Pharyngeal symptoms: These include sore or scratchy throat, odynophagia, or dysphagia. Sore throat is typically present in the first days of illness, although it lasts only a few days. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable sensation of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in a dry mouth, especially after sleep.
• Cough: This may represent laryngeal involvement, or it may result from upper airway cough syndrome related to nasal secretions (postnasal drip). Cough typically develops on the fourth or fifth day, subsequent to nasal and pharyngeal symptoms.
• Foul breath: This occurs as resident flora process the products of the inflammatory process. Foul breath may also occurs with allergic rhinitis.
• Hyposmia: Also termed anosmia, it is secondary to nasal inflammation.
• Headache: This symptom is common with many types of URI.
• Sinus symptoms: These may include congestion or pressure and are common with viral URIs.
• Photophobia or conjunctivitis: These may be seen with adenoviral and other viral infections. Influenza may evoke pain behind the eyes, pain with eye movement, or conjunctivitis. Itchy, watery eyes are common in patients with allergic conditions.
• Fever: This is usually slight or absent, but temperatures can reach 39.4°C (103°F) in infants and young children. If present, fever typically lasts for only a few days. In influenza infection, fevers may result in temperatures as high as 40°C (104°F).
• Gastrointestinal symptoms: Symptoms such as nausea, vomiting, and diarrhea may occur in persons with seasonal or H1N1 influenza, especially in children. Nausea and abdominal pain may be present in individuals with strep throat and viral syndromes.
• Severe myalgia: This is typical of influenza infection, especially in the setting of sudden-onset sore throat, fever, chills, nonproductive cough, and headache.
• Fatigue or malaise: Any type of URI can produce these symptoms. Extreme exhaustion is typical of influenza infection.

Bacterial pharyngitis

History alone is rarely a reliable differentiator between viral and bacterial pharyngitis. If symptoms persist beyond 10 days or progressively worsen after the first 5-7 days, a bacterial illness is suggested. Assessment for group A streptococci warrants special attention. A personal history of rheumatic fever (especially carditis or valvular disease) or a household contact with a history of rheumatic fever increases a person’s risk. Fever increases the suspicion for infection with group A streptococci, as does the absence of cough, rhinorrhea, and conjunctivitis, because these are common in viral syndromes. Other factors include occurrence from November through May and a patient age of 5-15 years.

• Pharyngeal symptoms: Sore or scratchy throat, odynophagia, or dysphagia are common. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable feeling of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Group A streptococcal infections often produce a sudden sore throat.
• Secretions: These may be thick or yellow; however, these features do not differentiate a bacterial infection from a viral one.
• Cough: It may be due to laryngeal involvement or upper airway cough syndrome related to nasal secretions (postnasal drip).
• Foul breath: This symptom may occur because resident flora process the products of the inflammatory process. Foul breath may also occur with allergic rhinitis.
• Headache: While common with group A streptococci and mycoplasma infections, it also may reflect URI from other causes.
• Fatigue or malaise: These may occur with any URI. Extreme exhaustion is typical of influenza infection.
• Fever: While usually slight or absent, temperatures may reach 38.9°C (102°F) in infants and young children.
• Rash: A rash may be seen with group A streptococcal infections, particularly in children or adolescents younger than 18 years.
• Abdominal pain: This symptom may occur in streptococcal disease or with influenza and other viral conditions.
• History of recent orogenital contact: This is relevant in cases of gonococcal pharyngitis. However, most gonococcal infections of the pharynx are asymptomatic.

Acute viral or bacterial rhinosinusitis

The presentation of rhinosinusitis is often similar to that of nasopharyngitis because many viral URIs directly involve the paranasal sinuses. Symptoms may have a biphasic pattern, wherein coldlike symptoms initially improve but then worsen. Acute bacterial rhinosinusitis is not common in patients whose symptoms have lasted fewer than 7 days. Unilateral and localizing symptoms raise the suspicion for sinus involvement.

• Nasal discharge: This may be persistent and purulent, and sneezing may occur. Mucopurulent secretions are seen with both viral and bacteria infections. Secretions may be yellow or green; however, the color does not differentiate a bacterial sinus infection from a viral one, because thick, opaque, yellow secretions may be seen with uncomplicated viral nasopharyngitis. Rhinorrhea is typically minimal or does not respond to decongestants or antihistamines. Congestion and nasal stuffiness predominate in some individuals.
• Hyposmia or anosmia: This may occur secondary to nasal inflammation.
• Facial or dental pressure or pain: In older children and adults, symptoms tend to localize to the affected sinus. Frontal, facial, or retroorbital pain or pressure is common. Maxillary sinus inflammation may manifest as pain in the upper teeth on the affected side. Pain radiating to the ear may represent otitis media or a peritonsillar abscess.
• Oropharyngeal symptoms: Sore throat may result from irritation from nasal secretions dripping on the posterior pharynx. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Mouth breathing may especially be noted in children. Dry mouth may be prominent, especially after sleep.
• Halitosis: Foul breath may be noted because resident florae process the products of the inflammatory process. This symptom may also occur with allergic rhinitis.
• Cough: Upper airway cough syndrome related to nasal secretions (postnasal drip) may result in frequent throat clearing or cough. Rhinosinusitis-related cough is usually present throughout the day. The cough may also be most prominent on awakening, occurring in response to the presence of secretions that have gathered in the posterior pharynx overnight. Daytime cough that lasts more than 10-14 days suggests sinus disease, asthma, or other conditions. Nighttime-only cough is common iumerous disorders, and many forms of cough are most noticeable at night. Upper airway cough syndrome related to nasal secretions occasionally precipitates posttussive emesis. Clinically significant amounts of purulent sputum may suggest bronchitis or pneumonia.
• Fever: This is more likely to occur in children than adults with rhinosinusitis. Fever may occur concomitantly with purulent nasal secretions in persons with sinus disease. In those with viral URI, fever, if present, typically precedes the development of purulent nasal secretions.
• Fatigue or malaise: These may be seen with any URI.

Epiglottitis

This condition is more often found in children aged 1-5 years who present with a sudden onset of symptoms:

• Sore throat
• Drooling, odynophagia or dysphagia, difficulty or pain during swallowing, globus sensation of a lump in the throat
• Muffled dysphonia or loss of voice
• Dry cough or no cough, dyspnea
• Fever, fatigue or malaise (may be seen with any URI)

Laryngotracheitis

• Nasopharyngeal symptoms: Nasopharyngitis often precedes laryngitis and tracheitis by several days. Odynophagia or dysphagia may be reported. Swallowing may be difficult or painful. Patients may experience a globus sensation of a lump in the throat.
• Hoarseness or loss of voice: This is a key manifestation of laryngeal involvement.
• Dry cough: In adolescents and adults, laryngotracheal infection may manifest as severe dry cough following a typical URI prodrome. Mild hemoptysis may be present.
• Barking cough: Children with laryngotracheitis or croup may have the characteristic brassy, seal-like barking cough. Symptoms may be worse at night. Diphtheria also produces a barking cough.
• Whooping cough: The classic whoop sound is an inspiratory gasping squeak that rises in pitch, typically interspersed between hacking coughs. The whoop is more common in children. Coughing often comes in paroxysms of a dozen coughs or more at a time and is often worst at night. The cough may persist for several weeks.
• Posttussive symptoms: Posttussive gagging or emesis may be present after paroxysms of whooping cough. Subconjunctival hemorrhage may result from severe cough. Rib pain, with pinpoint tenderness worsening with respiration, may result from rib fracture associated with severe cough.
• Dyspnea and increased work of breathing: Symptoms may be worse at night because of changes in airway mechanics while the patient is recumbent. Apnea may be a chief feature in infants with pertussis, or whooping cough. Apnea may also result from upper airway obstruction due to other causes.
• Other symptoms: Myalgias are characteristic in influenza infection, especially in the setting of hoarseness with sudden sore throat, fever, chills, nonproductive cough, and headache. Fever may be present, but it is not typical in persons with croup. Fatigue or malaise may occur with any URI.

Etiology

http://emedicine.medscape.com/article/219557-overview#aw2aab6b2b3aa

During the influenza pandemic of 1918 – 1919 filter-passing virus was more often considered to be influenza pathogen. This notion was confirmed by the classical experiments carried out by P. Zeiter who infected himself with washing off taken from the nasopharynx of an influenza patient and bacteriologically filtered.

In 1933 English scientists W. Smith, K. Andrews, P. Loudlow isolated influenza virus from a sick person, starting a new stage in the scientific study of the influenza etiological structure. In 1940 T. Frensis and T. Magil isolated a virus which was quite different from the ones isolated earlier. It was suggested to name the first virus – influenza type A virus, and the virus isolated by T. Frensis – type B. In 1947 R. Tailor isolated and described a new type of influenza virus which was later named type C.

The influenza pathogen belongs to the group of orthomyxoviruses. Virions have a ball form and a diameter of 100 – 120 nm, they have a core of a tightly turned spiral of ribonucleic acid in the case of protein molecules (Fig. 1).

On the external capsule there are glycoproteids in the form of a fence of pins: hemagglutinins (HA) and neuraminidase (NA) causing the development of a specific immunity after the disease.

The influenza virus quickly dies at drying, high temperature, it is resistant to low temperatures, extremely sensitive to ultraviolet rays and many disinfectants.

Influenza B virus has a more stable antigenic structure and doesn’t change so often. It has one neuraminidose but different hemagglutinins.

The most stable in relation to antigens is virus C. It causes only sporadic diseases and small outbreaks. It is spread mostly in Ukraine, Moldova and other southern regions.

Fig. 1. Influenza virions

http://emedicine.medscape.com/article/219557-overview#a0156

Epidemiology

 Influenza remains the most spread mass disease nowadays, which does not recognize any borders and affects great masses of the population (up to 50 % and more) at short periods of time. The influenza contagious character was noticed even in 1735 by Gexgame during the epidemic in Scotland, he called the disease «epidemicus».

A sick person is the only source of the disease. The epidemiological role of virus carriers has not been studied well. The virus quickly multiplies in the epithelial tissue of the respiratory tract mucous membrane of a sick person and in 24 – 48 hours there is an aerosol cloud with a great concentration of influenza virus around a patient at sneezing and coughing. As the immunity of a specific type forms very quickly, the virus disappears from the organism of a sick person on the fifth day of the disease.

Influenza infection is spread with the help of small particle aerosol dispersion. The mechanism of virus spreading is based on the condition that the virus is in the air for a long time, it has an ability to keep its infectious force under unfavorable conditions of the environment and the ability of virus particles to move with air at long distances and penetrate different parts of respiratory tracts infecting a person.

The influenza virus of full value can live and be infectious in the air for 2 -3 hours. It can live for 1 -2 days on the furniture and other surfaces. The ultraviolet rays, humidity decrease and temperature increase and other factors shorten the virus life time. The virus lives within the limits of 1 -3 meters. The speed of influenza spreading depends on the speed of people moving on the territory. The considerable increase of transportation, the movement of great numbers of people within separate countries, between countries and continents ensures a constant possibility of the virus spreading at considerable distances and the ability to infect people in any part of the globe.

There are small local epidemics and pandemics. The epidemics last 10-14 weeks.

The majority of people are naturally susceptible to influenza. The sick rate depends on many factors. First of all, on the level of the population specific immunity and on the circulation of the influenza virus serotypes.

The number of the influenza cases among adults has considerably decreased during the last years, as for the children aged 7 -14 the number of influenza cases is growing slowly but steadily.

The influenza B sick rate tends to grow in all the age groups.

http://emedicine.medscape.com/article/219557-overview#a0104

Pathogenesis

After penetrating the respiratory tracts, the virus sticks to the epithelial cells which have receptors – things of the lipid and carbohydratic nature. When the virus fixes on the cell surface receptors some complex enzymatic processes begin to occur, they ensure its penetration a cell in which it reproduces. This complex multistage process results in the cell death, and new virions born in the cells occupy new areas of the mucous membranes. The virus multiplication cycle lasts 7-10 hours. Every virion which penetrated a cell gives birth to 1000 virions and there will be 10²⁷ of them in a day. That’s why the influenza incubation period is so short.

Influenza viruses are encapsulated, negative-sense, single-stranded RNA viruses of the family Orthomyxoviridae. The core nucleoproteins are used to distinguish the 3 types of influenza viruses: A, B, and C. Influenza A viruses cause most human and all avian influenza infections.

The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most significant surface proteins include hemagglutinin (H) and neuraminidase (N).

Hemagglutinin and neuraminidase are critical for virulence, and they are major targets for the neutralizing antibodies of acquired immunity to influenza. Hemagglutinin binds to respiratory epithelial cells, allowing cellular infection. Neuraminidase cleaves the bond that holds newly replicated virions to the cell surface, permitting the spread of the infection.^[12]

Major typing of influenza A occurs through identification of both N and H. Sixteen N and 9 H types have been identified. All hemagglutinins and neuraminidases infect wild waterfowl, and the various combinations of H and N results in 144 combinations and potential subtypes of influenza. The most common subtypes of human influenza virus identified to date contain only hemagglutinins 1, 2, and 3 and neuraminidases 1 and 2. These variants result in much of the species specificity due to differences in the receptor usage (specifically sialic acid, which binds to hemagglutinin and which is cleaved by neuraminidase when the virus exits the cell).

The variants are used to identify influenza A virus subtypes. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2. H3N2 and H1N1 are the most common prevailing influenza A subtypes that infect humans. Each year, the trivalent vaccine used worldwide contains influenza A strains from H1N1 and H3N2, along with an influenza B strain.

The viral RNA polymerase lacks error-checking mechanisms and, as such, the antigenic drift from year to year is sufficient to ensure a significant susceptible host population. However, the segmented genome also has the potential to allow re-assortment of genome segments from different strains of influenza in a co-infected host.

Interspecies spread

In addition to humans, influenza also infects a variety of animal species. More than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. Influenza B has also been reported in seals, and influenza C, rarely, in pigs.

Some of these influenza strains are species specific. Species specificity of influenza strains is partly due to the ability of a given hemagglutinin to bind to different sialic acid receptors on respiratory tract epithelial cells. Avian influenza viruses generally bind to alpha-2,3-sialic acid receptors, whereas human influenza viruses bind to alpha-2,6-sialic acid receptors.

In this context, the term avian influenza (or “bird flu”) refers to zoonotic human infection with an influenza strain that primarily affects birds. Swine influenza refers to infections from strains derived from pigs.

New strains of influenza may spread from other animal species to humans, however. Alternatively, an existing human strain may pick up new genes from a virus that usually infects birds or pigs.

Antigenic drift and shift

Influenza A is a genetically labile virus, with mutation rates as high as 300 times that of other microbes. Changes in its major functional and antigenic proteins occur by means of 2 well-described mechanisms: antigenic drift and shift.

Antigenic drift is the process by which inaccurate viral RNA polymerase frequently produces point mutations in certain error-prone regions in the genes. These mutations are ongoing and are responsible for the ability of the virus to evade annually acquired immunity in humans. Drift can also alter the virulence of the strain. Drift occurs within a set subtype (eg, H2N2). For example, AH2N2 Singapore 225/99 may reappear as with a slightly altered antigen coat as AH2N2 New Delhi 033/01.

Antigenic shift is less frequent than antigenic drift. In a shift event, influenza genes between 2 strains are reassorted, presumably during co-infection of a single host. Segmentation of the viral genome, which consists of 10 genes on 8 RNA molecules, facilitates genetic reassortment. Because pigs have been susceptible to both human and avian influenza strains, many believe that combined swine and duck farms in some parts of Asia may have facilitated antigenic shifts and the evolution of previous pandemic influenza strains.

The re-assortment of an avian strain with a mammalian strain may produce a chimeric virus that is transmissible between mammals; such mutation products may contain hemagglutinin and/or neuraminidase proteins that are unrecognizable to the immune systems of mammals. This antigenic shift results in a much greater population of susceptible individuals in whom more severe disease is possible.

Such an antigenic shift can result in a virulent strain of influenza that possesses the triad of infectivity, lethality, and transmissibility and can cause a pandemic. Three such influenza pandemics have occurred in recorded history: the 1918 Spanish influenza (H1N1) pandemic and the pandemics of 1957 (H2N2) and 1968 (H3N2). Smaller outbreaks occurred in 1947, 1976, and 1977.

Avian influenza

To date, the vast majority of cases of avian influenza have been acquired from direct contact with live poultry in emerging nations. Hemagglutinin type H5 attaches well to avian respiratory cells and thus spreads easily among avian species. However, attachment to human cells and resultant infection is more difficult. The reasons why humans can be infected with H5 are poorly understood. Some of the earliest cases of human infection with H5N1 were observed during an outbreak of severe respiratory disease in Hong Kong in 1997. The outbreak was successfully contained with the slaughter of the entire local chicken population (around 1.5 million birds). However, only 18 human cases were reported, 6 of them fatal.

Note the image below.

Colorized transmission electron micrograph shows avian influenza A H5N1 viruses (gold) grown in MDCK cells (green).

Colorized transmission electron micrograph shows avian influenza A H5N1 viruses (gold) grown in MDCK cells (green). Image courtesy of Centers for Disease Control and Prevention.

Since then, H5N1 has been found in chickens, ducks, and migratory fowl throughout Asia and is now spreading west through Europe and North Africa. Human cases are following the route of the avian spread, but H5N1 has also been found in dead birds in several countries without any reported human cases (eg, the United Kingdom, Germany; see image below).

Global map of countries where avian influenza (bird and human infections) has been reported. Image courtesy of PandemicFlu.gov.

As of fall 2008, more than 390 human cases had been documented and more than 246 persons had died following H5N1 outbreaks among poultry and resulting bird-to-human transmission. Most human deaths due to bird flu have occurred in Indonesia. Sporadic outbreaks among humans have continued elsewhere, including China, Egypt, Thailand, and Cambodia.

To date, avian influenza remains a zoonosis, with no sustained human-to-human transmission. Family clusters have been reported but appear to be almost always related to common exposures; however, limited human-to-human spread through close proximity could not be officially ruled out. In September 2004, one case in Thailand probably involved daughter-to-mother transmission; the mother died.

At present, the poor transmissibility of the virus from human to human limits the extent of disease due to avian H5N1 influenza. The virus is continuing to undergo genetic changes, however, and experts are concerned that additional point mutations could convert H5N1 to a strain that is easily transferred from human to human. Such a strain has the potential to spread rapidly and precipitate a catastrophic worldwide pandemic.

The pathophysiology of avian influenza differs from that of normal influenza. Avian influenza is still primarily a respiratory infection but involves more of the lower airways than human influenza typically does. This is likely due to differences in the hemagglutinin protein and the types of sialic acid residues to which the protein binds.

Avian viruses tend to prefer sialic acid alpha(2-3) galactose, which, in humans, is found in the terminal bronchi and alveoli. Conversely, human viruses prefer sialic acid alpha(2-6) galactose, which is found on epithelial cells in the upper respiratory tract. One group has reported that ex vivo cultures of human tonsillar, adenoidal, and nasopharyngeal tissues can support replication of H5N1 avian influenza.

Although this results in a more severe respiratory infection, it probably explains why few, if any, definite human-to-human transmissions of avian influenza have been reported: infection of the upper airways is probably required for efficient spread via coughing and sneezing. Many are concerned that subtle mutation of the hemagglutinin protein through antigenic drift will result in a virus capable of binding to upper and lower respiratory epithelium, creating the potential for pandemic spread.

In contrast to human influenza, most deaths associated with avian influenza have been due to primary viral pneumonia, with no evidence of secondary bacterial infection.

Reservoirs for avian influenza A

Waterfowl, including ducks and geese, are considered to be the natural reservoirs for avian influenza A. Most infections in these birds are believed to be asymptomatic. However, because these viruses can also infect and cause disease in domestic poultry and because of the potential economic implications, substantial attention has been given to avian influenza.

 

If there were no obstacles for reproduction, the entire tissue of the respiratory tract would be affected in 1-2 days and it would result in a lethal outcome. It happens in rare cases – «quick influenza» develops and a patient dies in 2 days. But it doesn’t usually happen so, because a cell, in which virus reproduces, produces and secretes interferon. This interferon gets into the neighboring cells and after that they are not defenseless against the virus invasion. Interferon prevents virus protein from synthesis. The further development of virus infection depends on the struggle of these two forces -virus genome and cell interferon: either it stops at the very beginning or the disease lasts a short time and a patient gets well or the infection spreads in the lungs and fatal pneumonia develops.

The cells affected by a virus are rejected and the products of their decomposition are absorbed, causing a general feverish disease. At the same time in the submucous membrane there develop inflammatory processes with distinctive circulatory disorders, that clinically manifests by hemorrhage syndrome.

When the process spreads in the lung tissue, in severe cases with the development of influenza pneumonia, there are signs of general edema with scattered or confluent foci of hemorrhage.

Under these conditions the influenza virus easily penetrates the blood and virusemia develops. However, virusemia at influenza doesn’t last long, as the virus quickly dies under the influence of nonspecific immunity factors -interferon, complement, properdin, β-lysines, β-inhibitors, histones, leukins, etc.

It is quite possible that the affection of the internals at influenza is connected with virusemia. However, the great maiority of authors doubt the specificity of such affections, as there are no specific receptors in all the other organs, and they think that in the pathogenesis of affections the leading role doesn’t belong to the cytopathogenic phenomena, it belongs to the organism reaction to toxic products or other substances, which appear at the influenza virus reproduction process.

Besides, it is a fact that even in the mild cases of the disease there are signs of the organism hem poetic and immune system considerable depression. The number leukocytes in blood decreases and their functions are suppressed. Macrophages become less active. Due to it bacteria and viruses become more active and the accompanying diseases take an acute form. Influenza «opens» the gate for the enemy, that’s why it is called after Tarpeya, a legendary traitor, who opened the gate of Rome for the enemies. So influenza infection is mostly a combined virus-bacterial or virus-virus infection.

In conclusion it is necessary’ to note that interferon production is very important for the disease outcome in the struggle between viruses and the organism protective forces. Antibodies of class IgM appear only at the end of the first week of the disease when the organism wins the first main battle, and antibodies of class IgG in two weeks.

Pathologic Anatomy.

There are three main groups of pathoanatomic changes at influenza: the first one – primary changes, caused by the virus itself; the second ones – secondary changes, caused by influenza virus in combination with cocci and bacterial flora; the third ones – late changes in patients who had influenza and died of complications or worsening of other diseases.

The most important morphological signs of the first group are dystrophic changes of the respiratory epithelium and lungs with distinctive disorders of microcirculation; sharp plethora, edema and pericellular infiltration of submucous membrane and thickening of basal membrane.

The interalveolar septum of lung tissue are considerably thickened due to plethora and edema with leukocytic-lymphoid infiltration. The walls of small vessels and capillaries are thickened, in some vessels there are fibrous and leukocyte thromboses. The cells of alveolar epithelium became partially hyperplastic, in some places – died, there is a small microphagic exudate in the alveoli lumens.

In the second group there remain signs of pure influenza infection, but more or less they are prevailed by the purulent affections of the respiratory system and serious blood circulation disorders in the lungs. Pyo-hemorrhagic and pyo-necrotic tracheitis with a destruction of epithelium is developed in trachea. The lung tissue is low-pneumatic, the surface of the incision is motley, with alternation of large dark-red and gray foci. During microscopy massive foci of pyo-hemorrhagic pneumonia are found.

In the third group there are different kinds of pneumonia with various inflammatory exudate: purulent, pyo-hemorrhagic and abscess, plethora, edema and in some places hemorrhages into parenchymal organs, and also changes, which are characteristic of the accompanying chronic diseases.

http://emedicine.medscape.com/article/219557-clinical#showall

Clinical  manifestations

The incubation period at influenza is short – from several hours to 2 -3 days. Its duration depends on the dose and toxic characteristics of the virus. The incubation period is short if the dose is big and the virulence is considerable. Thus, its duration has a prognostic meaning for a doctor.

There have been different opinions about the preliminary symptoms of the disease. It should be admitted that there is a prodromal period, which is characterized by an elevated temperature for a short period of time (2-3 hours), slight malaise, chilliness, myalgias. These symptoms don’t last long and are usually ignored by both a patient and a doctor. The disease begins to develop on the next day. In some patients the disease develops so fast that a practically healthy person becomes seriously ill in several minutes or hours.

The first symptoms are chilliness (always more or less manifested), high temperature, headaches, dizziness, a syncope condition, fever, malaise, pains in different parts of the body i.e. the symptoms of general intoxication. The headache is located in the forehead, temples and over the brows, it can be of different intensity. There is an early distinctive symptom – pain in the eye pupils especially intense at the eye movement or pressing, hyperemia of conjunctivas and sometimes scleras. Dizziness and syncope conditions are characteristic of teenagers and old people. The fever which is one of the main symptoms of influenza does not last long – 1-4 days (in 86% patients). The ‘two-humped’ character of the temperature is connected with the condition when the chronic infection takes an acute form or a secondary flora joins. Such symptoms as unconsciousness, delirium, convulsions and meningeal manifestations are characteristic of children at intense toxicosis.

Such symptoms as malaise, pains in the limbs and muscles, bones or in the whole body appear during the first hours of the disease and disappear when fever and other signs of toxicosis decrease. Adynamia, malaise can be considerable and are manifested from the first day of the disease. The skin on the face is hyperemic during the first 2-3 days, in severe cases they become pale with cyanotic shade. It is often a bad prognostic sign. Sweating is a characteristic feature. Intoxication is a characteristic feature of influenza, its degree and frequency vary in case of different microbes. In different epidemics there is hemorrhage syndrome, in 10 -20% cases, its symptoms are nasal bleeding, sometimes reciprocal, hemorrhage in the fauces, metrorrhagia, short hemoptysis and gum bleeding sickness. Cough appears during the first days of the disease, dry, excruciating, heart-rending which is accompanied by the feeling of tickling, scratching behind the breast bone. Almost all the patients have a catarrhal syndrome which has such symptoms as rhinitis, pharyngitis, tracheitis. There are often such combined affections of the mucous membrane as rhinopharyngitis, laryngotracheitis, tracheobronchitis, etc. They usually appear in the first days of the disease. Such symptoms as herpetic rash is quite frequent, but appears; on the  3^rd-4^th  day. Photophobia and lacrimation are finite rare.

There are no specific changes on the skin. Different kinds of rash which were described result from other reasons (taking drugs, accompanying diseases). As it has been mentioned before, quite often there is herpetic rash, theoretically there is a possibility of petechiae, hemorrhages, if we take into consideration the affection of vessels and their hyperpermeability. There can be random rash.

A natural manifestation of the influenza infection is the affection of the respiratory organs, as different pathological processes take place in them, they are located on a certain level, but sometimes affect the entire area. The affection of the upper respiratory tracks is accompanied with hyperemia and swelling of mucous membrane, sometimes with slight hemorrhages. There is nasal obstruction, rough breathing, and discharge of different nature and consistence: mucous, mucopurulent and sttaguinolent – in severe cases. During rhinoscopy swelling and hyperemia of mucous membrane can be seen, especially at the middle turbinated bone. At the same time accessory nasal sinus can be affected (maxillary sinusitis, frontal sinusitis, eustachitis with the development of otitis) with different nature of affection – from catarrhal to purulent.

During fauces examination the hyperemia of tonsils, uvula palatina and posterior wall of the throat could be found. Sometimes there are granules with vascular injection and hemorrhages on the soft palate. The development of influenza laryngitis and false croup is extremely dangerous, especially in children. Patients become pale, cyanosis develops, they often breathe with the help of additional musculature, the voice remains. Lethal outcomes are not rare, because not only larynx is affected, but trachea and bronchi as well, they are full with croupous superposition. The swelling of the mucous membrane of trachea and bronchi results in their permeability and leads to the deterioration of lung ventilation. Depending on the severity of the disease the degree of manifestations is different – from the hidden forms, which can be found with the help of pharmacological tests (aerosolic injection of eusporinum) to the severe forms accompanied with dyspnea and cyanosis. The most common and dangerous complication of influenza is pneumonia. It is necessary to mention, that even during the first days of the disease there are roentgenologic strengthening of the vessel picture in the inferiomedial parts, that looks like indistinct infiltrate, and hurried breathing, shortening of the percussion sound and appearance of so called «conductive» rhonchi, resemble pneumonia. But they often disappear without any traces in 2 – 3 days. It may not be pneumonia, but some circulatory disorders. Not everything is clear in the problem of pneumonia origin. After the detection of pathogen it was considered that during the first three days pneumonia is of virus etiology, on the 3 -5 day – virus-bacterial, later – bacterial etiology. There is a picture of the so called «big motley lung» on the section. Hemorrhage pneumonia foci of different sizes can be seen along the whole length, they are small and large and separated by some parts of unaffected tissue. The foci of festering appear quite early. The rough beginning with severe toxicosis, catarrhal syndrome, significant and diverse changes in the lungs, are characteristic of influenza infection, which is complicated with pneumonia.

Diverse changes in the cardiovascular system have been described. The vascular system is usually affected, and sometimes considerably, it is probably connected with a toxic action of influenza virus on capillary vessels. Dilation of capillaries, turbid background, sometimes formation of the arterial aneurysms, are seen at the capillaroscopy. Arterial and venous pressure decreases, especially in case of pneumonia, the speed of blood flow slows down. The pulse is very often corresponds the fever, there is sometimes tachycardia, especially at the beginning of the disease, in some cases there is bradycardia. The heart sounds are muffled, heart borders are widened, slight systolic murmur and sometimes extrasystoles appear. All these manifestations disappear when the general condition of the patient becomes better. There is elongation of the PQ interval, decreasing and notching, and sometimes inversion of the wave T at different abductions on the ECG. These disorders are interpreted as toxic and dystrophic. They are unstable and disappear in 1 – 2 weeks. The myocarditis described at influenza is disputed by other authors. More severe and diverse disorders are found in patients with chronic affections of the cardiovascular system (coronary atherosclerosis, rheumatic heart diseases, etc.). These disorders are not pathognomonic for influenza, and arise because of the aggravation of the main disease under the influence of influenza infection.

There are various affections of the nervous system during the influenzal infection. The functional disorders of the vegetative nervous system are distinctively manifested. We have already got acquainted with such symptoms as sweating, changes of the pulse rate, dizziness, etc. However, all these changes quickly disappear. At the same time serious affections of the central and peripheral nervous systems are observed, they are manifested as meningitis, meningoencephalitis, radiculitis, neuritis, etc. The rate of these complications is different in different epidemic outbreak. The pathogenesis of these diseases is still a difficult question. Side by side with the theories of the toxic and parainfectious factors in their development, it is possible, that the virus invasion plays a significant role.

The complications in the digestive system are less often, and there are evidently no specific disorders, although fur, dryness in the mouth, decreased appetite, and heaviness in the epigastrium are observed. These symptoms are characteristic not only of influenza, but of any disease with fever. And now such forms of influenza as gastrointestinal, intestinal and abdominal which were the results of diagnostic mistakes are mentioned in conversations but not in literature.

The changes in the urinary tracts are manifested as pyelitis, pyelocystitis and sometimes nephritis, which result from metabolic-dystrophic manifestations of fever and bacterial superinfection.

The described affections of the endocrine system (adrenal gland, thyroid and pancreas glands) are very rare and it is not possible to completely exclude the influence of influenza virus in these cases.

The changes in the hemogram are manifested as leukopenia or normocytosis. If there are no complications and accompanying diseases, there is absence or decrease of the eosinophils, neutropenia and relative lymphocytosis in the hemogram at influenza (the percentage of lymphocytes increases whereas their absolute number is the same). ESR is normal or insignificantly increased. The connection of the bacterial complications is accompanied with leukocytosis and neutrophilia. It is important to take into account the absolute number of elements of white blood in the dynamic of the disease.

http://emedicine.medscape.com/article/219557-differential

Differential diagnosis

Besides careful clinical and epidemiological findings, modern methods of lab diagnostics are used for influenza diagnosis and differential diagnosis of other diseases.

Diagnosis does not seem to be difficult during epidemic outbreaks. However, at the same time besides influenza there 30-60% patients with the respiratory tracts affection syndrome are registered, they are not of the influenza etiology, and clinical diagnosis is even more difficult during a non-epidemic period. As we see, influenza doesn’t have specific symptoms which are characteristic of it only, but there are 3 strongly pronounced symptoms: abrupt onset with chilliness, general intoxication and the affection of the upper respiratory tracts. But they also accompany other acute respiratory diseases, and that is why there are many cases when patients with the diagnosis «influenza» are taken to hospital, but they have different other infectious and non-infectious diseases. That is why it is always important first of all to take into account the epidemic situation in the region.

A short incubation period is characteristic of influenza that is why the contacts with sick people, especially in the foci 1-3 days before the disease should be taken into account. If it is possible it is advisable to make up a general conception of the disease clinical picture in the people the patient contacted.

A careful and detailed physical examination of the patients, analysis and a comparative evaluation of the reveled changes with the consideration of the time past from the disease onset is also of great importance. It is important to remember that the preceding therapy can have a considerable influence on the natural disease course, sometimes changing or allaying some symptoms, and in other cases, on the contrary, resulting in the development of the new symptoms with are not typical of influenza. These can be various manifestations of the medication disease: skin rash, lymphoadenopathy, the toxic affection of the liver, hemogenic system, development of asthmatic syndrome, etc. Only a careful analysis of all the clinical symptoms can reveal the main syndromes, the peculiar mosaic of which is characteristic of one or another nosological form.

There is not any typical temperature curve. A relatively short febrile temperature reaction (5-6) days with a quick rise and maximum values during the first 2-3 days and shortened lysis should be considered to be more or less typical if the fever lasts longer than this period, it is always necessary to think of a possibility of another disease or joining of a complication. The usage of antibiotics, analgetics, sulfanilamides and glucocorticoides can considerably change a natural course of the temperature curve.

An intoxication syndrome is the main in influenza, and various symptoms of the syndrome can be expressed in different ways and occur in different combinations. A headache and general malaise are the most frequent. But they are typical of many other diseases, mainly the infectious ones, and do not have a diagnostic value. In influenza there is no skin rash except a herpetic one. In acute meningitis of different etiology there is a complete or incomplete meningeal syndrome and typical changes of the spinal liquor. It is not meningitis but meningism that is typical of the severe hypertoxic form of influenza, meningism is characterized with incomplete meningeal syndrome, liquor hypertension without any inflammatory changes in the spinal liquor, the spinal puncture solves the diagnostic problem in these cases.

The development of edema swelling of brain – is accompanied by sopor, coma, convulsions, olygopnoe and bradycardia. These condition should be distinguished from coma and convulsion syndrome of another nature. A general malaise, dizziness, fainting, asthenisation, do not have a diagnostic value, but in combination with a headache and retroorbital pains as well as with catarrhal symptoms might help diagnose influenza. Nasal bleeding is the most frequent manifestation of the hemorrhagic syndrome in influenza, but they also occur in-other diseases and can help in diagnostics only in combination with other characteristic symptoms. The appearance of the blood admixture in sputum is almost always a bad symptom. Acute hemorrhagic toxic edema of the lungs is one of the variants of hypertoxic influenza, its clinical symptoms are asphyxia, cyanosis, bubbling breathing and liquid pink foamy sputum. It must be distinguished from poisoning connected with breathing in vapors of poisonous substances, acute left ventricular heart insufficiency. Taking into account the epidemic situation, high temperature, intoxication and tracheitis can help diagnose influenza.

The appearance of sputum containing blood (pus and blood) in influenza, which is complicated by pneumonia, often testifies about the latter’s staphylococcus nature. The pleura is often involved in the pathological process, severe respiratory and cardiovascular insufficiency develops. Hemorrhagic pneumonia and influenza should be distinguished from the croup pneumonia. In croup pneumonia there are no symptoms of the upper respiratory tract affection which are characteristic of influenza, the disease has a sudden onset with pains in the side and sudden temperature rise, there is “liver” dullness over the affected lobe and bronchial breathing with the following development of moist rale, the sputum is rusty though there can be admixture of crimson blood in it.

The fever and vomiting, which are observed in influenza may be diagnosed as alimentary toxic infection of salmonelesis or another etiology. But in influenza there are other symptoms of intoxication which are considerably expressed, they are combined with the nose stuffing, tickle in the throat, pain behind the sternum and dry cough. Sometimes even in influenza there are pains in the upper part of abdomen stipulated by mialgia. Diarrhea often occurs in this disease. That is why in case of moderate toxicosis, vomiting, pains in the abdomen and frequent watery stool with an admixture of slime and blood it is necessary to think of some acute alimentary disease, but not influenza.

The development of symptoms of the upper respiratory tract in influenza makes one distinguish this disease from other acute respiratory diseases caused by adenoviruses respiratory–syncytial viruses, paragrippal viruses, rhinoviruses, reoviruses, coronaviruses, ECHO–viruses, Koksaky viruses, mycoplasma pneumonia.

The catarrhal syndrome in influenza develops later and is less expressed than intoxication. Tracheitis, to be more exact laryngotracheitis is the main syndrome in influenza. Scattered dry rale together with hard breathing develop when the inflammatory process spreads along the bronchial tree. The symptoms of laryngotracheitis stay even in case of the development of pneumonia or other complications, this helps to suspect influenza as the main disease. Rhinitis and pharyngitis in influenza do not always occur and have peculiarities in the form of dryness and stagnant hyperemia of the nose and throat mucous membranes, absence of scanty discharge from the nose, spontaneous nasal bleeding.

Adenoviral infection is characterized by a more prolonged incubation period (7-14) days.

Adenovirus, a DNA virus, was first isolated in the 1950s in adenoid tissue–derived cell cultures, hence the name. These primary cell cultures were ofteoted to spontaneously degenerate over time, and adenoviruses are now known to be a common cause of asymptomatic respiratory tract infection that produces in vitro cytolysis in these tissues.

A virus image from the International Committee on Taxonomy of Viruses, in The Big Picture Book of Viruses, available at http://www.virology.net/Big_Virology/BVDNAadeno.html.

An extremely hardy virus, adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic throughout the year. Possessing 52 serotypes, adenovirus is recognized as the etiologic agent of various diverse syndromes. It is transmitted via direct inoculation to the conjunctiva, a fecal-oral route, aerosolized droplets, or exposure to infected tissue or blood.

The virus is capable of infecting multiple organ systems; however, most infections are asymptomatic. Adenovirus is often cultured from the pharynx and stool of asymptomatic children, and most adults have measurable titers of anti-adenovirus antibodies, implying prior infection. Adenovirus is known to be oncogenic in rodents but not in humans.

Adenovirus has been associated with both sporadic and epidemic disease and, with regard to infections among military recruits, is a significant cause of economic cost and morbidity because of the cessation of vaccine production in 1996.

Of most recent interest is the role of adenoviruses as vectors in vaccination and in gene therapy. Adenoviruses can infect various cells, both proliferating and quiescent, and thus hold the promise of targeting many different tissues and diseased cell lines.

The genome of adenovirus is well known and can be modified with relative ease to induce lysis or cytotoxicity of a specified cell line without affecting others.

The virus itself can be engineered to remove its replicative capacity by removing essential genes. Additionally, specific genes can be inserted into the virus that then can repair defective metabolic, enzymatic, or synthetic pathways in the host. Suicide gene systems that convert nontoxic systemically delivered prodrugs to active chemotherapeutic agents have been delivered via adenoviral vectors directly into cancer cells. However, the greatest challenge in viral gene therapy, as might be expected, is the immune response to the viral vector itself.

The complex mechanisms by which viral vectors may be incorporated into gene therapy and the rapid growth in this field put further discussion beyond the scope of this text.

The fact that there are simultaneous cases with various clinical picture in the foci of adenoviral infection is a characteristic feature; the clinical picture: acute rhinitis, rhinopharyngitis, pharyngoconjunctivatis, covering conjunctivitis, exhantema, hepatolienal syndrome, etc. A less acute than in influenza onset, moderate intoxication in spite of the high and sometimes prolonged temperature reaction is typical of the adenoviral infection.         However the syndrome of intoxication is less important as compared with the expressed catarrhal changes on the part of upper respiratory tract and conjunctiva, which are of exudative character. The pathological process sort of “crawls over” from one zone to another, and the involvement of each new are of the respiratory tract is accompanied with a temperature rise which results in the two or three top character of the temperature curve. Together with this or some time later peculiar tonsillitis may develop together with exudative pharyngitis which manifests itself with edema and bright hyperemia of the back wall of the throat, on which one can see hypertrophic lymph follicles. If the disease starts with rhinitis (it can be limited by it), the discharge from the nose can be abundant, serouse. Laryngitis and tracheitis in contrast to influenza are not characteristic of adenoviral infection.

History

Because the manifestations of adenovirus infections are protean, the major syndromes are discussed separately. The major syndromes (1) acute respiratory disease (ARD), (2) pharyngoconjunctival fever, (3) epidemic keratoconjunctivitis, (4) acute hemorrhagic cystitis, (5) gastroenteritis, and (5) adenoviral infections in immunocompromised hosts.

Given the range of manifestations, the varying levels and effects of immunosuppressive therapies, and rapid advances in molecular methods of detection, a comprehensive review of adenovirus infection in the immunosuppressed host is beyond the scope of this article; however, the author plans to report the most salient features and general updates here. The reader is encouraged to review the literature for more detail regarding infection in specific settings.

• Acute respiratory disease (predominantly adenovirus types 1, 2, 5, and 6; occasionally, 3 and 7)
• As with many other viral syndromes, ARD is more common in spring and winter months. Approximately half of adenovirus respiratory infections do not cause symptoms. Adenoviruses account for 10% of all childhood lower respiratory tract infections.
• The contagiousness of adenovirus is facilitated by very high levels of viral particles (100,000-1,000,000/mL) in the sputum or oral secretions of infected adults. Additionally, adults who lack antibody may be infected by the inhalation of as few as 5 virions in droplet nuclei.
• Fever, rhinorrhea, cough, and sore throat, usually lasting 3-5 days, are typical symptoms of adenoviral ARD. Causes of sore throat may include pharyngitis, adenoiditis, or tonsillitis. Tonsillitis and otitis media were reported in up to 60% and 30%, respectively in a series of young children with serotype 4 predominance. Prolonged fevers, leukocytosis, and elevations in C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also noted in over half of cases, suggesting potential for confusion of this viral syndrome with bacterial infections.
• Lower respiratory tract infections, including tracheobronchitis, bronchiolitis, and pneumonia, may mimic respiratory syncytial virus infection or influenza. Notably, conjunctivitis in the presence of bronchitis suggests adenoviral infection.
• Fatal pneumonia is uncommon but is more likely ieonates and has been associated with serotypes 3, 7, 14, 21, and 30.
• Encephalitis, hepatitis, and myocarditis are uncommon.
• From the 1950s to 1971 (prevaccine era), adenoviruses accounted for significant acute disease in 70% of military recruits. Adenovirus serotypes 4 and 7 were primarily involved. A live enteric-coated oral vaccine against these serotypes was introduced in 1971 and reduced adenovirus-related respiratory illness by more than 95% in recruits and thus attenuated outbreaks. Vaccine production ceased in 1996 for economic reasons, and vaccination administration was limited to high-risk periods until supplies ran out in 1999. In 1997, a large epidemic of more than 500 cases associated with serotypes 3 and 7 occurred in US Navy recruits. Most recent analyses suggest that serotype 4 has caused most military outbreaks since 1999, with the exception of Ad14.
• Adenovirus serotype 14
• Ad14, referred to as the “super cold” in the media, has caused rare outbreaks of ARD since 1955.
• Between May 2006 and June 2007, 141 cases of Ad14 infection were reported in clusters in New York, Oregon, Texas, and Washington. Almost 40% of affected persons were hospitalized, almost half in intensive care, with a 5% overall mortality rate. The cases in Texas involved military trainees at Lackland Air Force Base, and subsequent cases were reported at Lackland, three other Texas military bases, and one eye culture in a civilian unassociated with the military. Adenovirus may be isolated from children with whooping cough syndrome in the presence or absence of Bordetella pertussis infection; however, whether adenovirus is an etiologic cause of the syndrome remains unclear.
• Pharyngoconjunctival fever (predominantly serotypes 3, 4, and 7)
• This syndrome most often affects school-aged children. Contagious iature, sporadic outbreaks of adenovirus infection occur in small groups, especially summer camps in the setting of an inadequately chlorinated water source such as a pool or lake. Interestingly, water sample cultures are ofteot confirmatory. Spread occurs via the respiratory route and contact with ocular secretions during the acute illness.
• The classic presentation is characterized by fever, sore throat, coryza, and red eyes. Upper respiratory tract symptoms may precede ocular findings or may be absent.
• Acute conjunctivitis may occur with or without pharyngitis or a respiratory syndrome. Encephalitis may occur but is rare.
• Conjunctivitis usually begins in one eye and then spreads to the other, although both eyes may be affected simultaneously. Severe pain is atypical, but mild pain or discomfort, tearing, pruritus, and morning crusting are common.
• It usually is self-limited to 5 days (incubation period is 5 d).
• Uncommonly, an exanthem or diarrhea may occur.
• Epidemic keratoconjunctivitis (predominantly serotypes 8, 19, and 37)
• This is highly contagious, with approximately 10% transmission in household contacts via hands and fomites. Transmission has also been associated with instrumentation, industrial trauma (shipyard workers [ie, shipyard eye], welders, airborne particles), contaminated ophthalmic solutions, and the hands of health care workers. Corneal trauma facilitates infection.
• After an 8-day incubation period, an insidious onset of unilateral red eye occurs, spreading to involve both eyes. Patients have photophobia, tearing, and pain (indicating corneal involvement). Children may have fever and lymphadenopathy.
• Malaise and headache are reported.
• Inflammation may persist for weeks, and residual scarring and visual impairment may occur.
• Acute hemorrhagic cystitis (serotypes 11 and 21)/nephritis
• Acute hemorrhagic cystitis usually affects children aged 5-15 years but may also affect immunosuppressed adults (eg, from kidney or bone marrow transplantation, AIDS). Boys are affected more often than girls.
• Dysuria, frequency, and grossly bloody urine are reported. Hematuria is self-limited to 3 days, and other symptoms resolve later. Symptoms may be more prolonged in hematopoietic stem cell recipients.
• Nephritis has occurred in recipients of hematopoietic stem cell transplants and is associated with fever, hematuria, and flank pain.
• Gastroenteritis (most commonly associated with serotypes 40 and 41, but others may be involved)
• Enteric adenovirus infection is a common cause of infantile diarrhea in the daycare setting, but less common than rotavirus infection and, in some settings, less common than infection with astroviruses. It can also affect adults; in addition, a nosocomial outbreak in a hematology unit has been reported. Adenoviruses replicate readily in the human intestine and may be cultured from asymptomatic individuals; thus, their presence in the setting of a diarrheal syndrome may be incidental.
• Many serotypes are fastidious in culture. Serotypes 40 and 41 had been termed “noncultivatable.” However, they have been cultured in the setting of diarrheal syndromes using newer cell lines. Monoclonal antibody assays, enzyme-linked immunosorbent assay, and electron microscopy support the association of these strains with enteric disease. However, one cannot assume that enteric disease is limited to these strains. In fact, various serotypes of adenovirus have been associated with infectious diarrheal syndromes in recipients of hematopoietic stem cell transplants.
• Fever and watery diarrhea are usually limited to 1-2 weeks.
• Mesenteric adenitis and intussusception have been associated with nonenteric adenovirus serotypes (ie, types 1, 2, 3, 5, 6). Approximately 40% of infants with intussusception have positive findings from cultures of stool or mesenteric lymph nodes for nonenteric serotypes, and most have no evidence of infection with enteric strains (ie, 40, 41). The role of adenovirus in this setting is unclear. Mesenteric lymphadenitis or hyperirritable small bowel associated with nonenteric adenoviral infection has been postulated to lead to intussusception. However, most patients with intussusception have no evidence of adenoviral infection (based on culture, serology, or histopathologic viral inclusion findings); thus, intussusception may be related to multiple etiologies.
• Adenoviral infections in immunocompromised hosts (multiple serotypes)
• Adenovirus is increasingly known to cause disease during the posttransplantation period in patients who have received hematopoietic stem cell transplants. Risk factors for adenovirus disease include allogeneic stem cell transplantation, T-cell depletion and nonmyeloablative conditioning regimens such as high-dose alemtuzumab (Campath) antibody therapy, lymphopenia, young age, and graft versus host disease. Prolonged neutropenia or immunosuppression also enhances the risk of adenoviral infections. Manifestations may vary but include hemorrhagic cystitis/nephritis, pneumonitis, hepatitis/liver failure, and gastroenteritis, particularly during the acute posttransplantation period prior to engraftment. In one series, nephritis was associated with acute renal failure in more than 90% of patients. Adenovirus should be considered in patients with a fever, hematuria, flank pain, and worsening renal function.
• Uncommonly, T-cell immunodeficiency related to HIV infection has been associated with adenoviral infections, particularly in infants and children infected with HIV. Pneumonitis and hemorrhagic cystitis are cited most often. Cholecystitis, severe hepatitis, and liver failure have been reported.
• Immunosuppression in recipients of solid organ transplants has also been associated with the above syndromes, as has diffuse adenoviral infection of the allograft itself. Both allograft loss and recovery have been reported. Adenoviral infection following pediatric lung transplantation has been reported.
• Importantly, note that a prior history of adenoviral infection in a patient with recovered immunocompetence may herald recurrence when the patient again becomes immunosuppressed. A high level of suspicion for adenovirus is warranted in these cases.
• General considerations
• Pulmonary infiltrates are often diffuse and reticulonodular, but they may be lobar.
• Hematuria may occur in the setting of nephritis or hemorrhagic cystitis.
• Abnormal transaminase levels, which may be dramatic, may indicate adenoviral hepatitis.
• Diarrhea may indicate adenoviral gastroenteritis.

Clinical manifaststion:

• Acute respiratory disease
• Exudative pharyngitis and conjunctivitis may be seen.
• Pulmonary rhonchi and rales may be found on auscultation.
• Pharyngoconjunctival fever
• Fever, coryza, pharyngitis (may be exudative), follicles in bulbar, and/or palpebral conjunctivae (typically mild granular appearance) may be observed.
• Cervical lymphadenopathy may be seen.
• Preauricular lymphadenopathy (ie, Parinaud syndrome), with small lymph nodes palpable just anterior to the ear is not common; however, its presence in the setting of a viral conjunctivitis is very suggestive of adenovirus infection.
• Epidemic keratoconjunctivitis
• Severe follicular keratoconjunctivitis has been reported (conjunctiva may be granular). Hemorrhagic conjunctivitis develops in some cases.
• Palpebral edema is a finding.
• Preauricular lymphadenopathy is not common but is a pathognomonic finding with adenovirus infection.
• Visual haziness or impairment resulting from keratitis or corneal involvement may develop and may persist for months to years.
• Acute hemorrhagic cystitis/nephritis
• No significant features are described in the setting of hemorrhagic cystitis, other than evidence of blood in the urine. Fever is generally absent.
• Flank pain and fever are seen iephritis.
• Gastroenteritis: Patients with severe gastroenteritis may have signs of dehydration.
• Adenoviral infections in immunocompromised hosts: Features include dyspnea, dry cough, pulmonary rhonchi and rales, grossly bloody urine, and diarrhea.

If the adenoviral infection is complicated by pneumonia, in adults it has approximately the same course as a moderate severe affection of the lungs in influenza and can be cured by usual antibacterial therapy. The adenoviral infection itself preserves its main clinical features, which allow to distinguish it from influenza. In case of the combination of influenza and adenoviral infection the disease has the symptoms characteristic of both nosological forms.

The respiratory-syncytial infection (RS) in adults is usually a sporadic disease, which equally effects all the age groups.

Infection with respiratory syncytial virus (RSV; see the image below), which manifests primarily as bronchiolitis or viral pneumonia, is the leading cause of lower respiratory tract infections (LRTIs) in infants and young children.

Electron micrograph of respiratory syncytial virus (RSV). RSV is most common cause of bronchiolitis and pneumonia in children younger than 1 year. Image courtesy of Centers for Disease Control and Prevention.

The clinical entity of bronchiolitis was described at least 100 years ago. In 1956, Morris and colleagues initially isolated RSV from chimpanzees with upper respiratory tract infections (URTIs) and identified the virus as the causative agent of most epidemic bronchiolitis cases. Subsequently, RSV has been associated with bronchiolitis and LRTI in infants. Multiple epidemiologic studies have confirmed the role of this virus as the leading cause of LRTI in infants and young children.

The peak incidence of severe RSV disease is at age 2-8 months. Overall, 4-5 million children younger than 4 years acquire an RSV infection each year.

In contrast to influenza the disease does not often have acute onset. The intoxication syndrome is expressed moderately or slightly. The temperature is subfebrile or moderately febrile. The changes of the upper parts of the respiratory tract are slightly expressed. The symptoms of acute bronchitis which are often accompanied with bronchial spastic component (continuous cough that is dry or has some scanty sputum, scattered dry rale and rare medium bubbling moist rale, prolonged inhaling, difficult exhalation, swelling of the lungs and others) dominate. The liver gets involved more often in the respiratory-syncytial viral infection in adults than in other acute respiratory diseases. At the high point of the disease it is enlarged and sensitive at pulpation, the Orthner symptom becomes positive (pain at beating on the costal arc).

Paragrippal diseases in adults like RS-infection have a more gradual onset the intoxication is slight or moderate as well as the temperature reaction, which in fact lasts longer than in influenza. Rhinitis and pharyngitis are moderately expressed, laryngitis is considered to be typical. There is no syndrome of false croup in adults as compared with children.

The rhinoviral infection occurs only in adults. The disease is characterized with subfebrile or normal temperature, slight intoxication symptoms or their complete absence and expressed exudative inflammation of the nose mucous membrane with abundant rhinorea, which is the main clinical symptom.

The coronaviral infection is also not severe disease, which is difficult to distinguish from a rhinoviral one and which affects not only adults but also children, and besides rhinitis the patients may have slight pharyngitis and even bronchitis.

ECHO- and Koksaky viruses can cause the diseases with affection of the upper respiratory tract. But the involvement of the brain meninx and spinal radices in the pathological process is more characteristic of the enteroviral infection.

Mycoplasma pneumonia can cause a respiratory disease in adults. It has a gradual onset and has a course with both low and febrile temperature, relatively slight symptoms of intoxication, slight affection of the upper parts of the respiratory tract, prolonged and persistent bronchitis.

The disease named “legionaries” disease is given to a new disease, which appeared in 1976 in the USA, its bacteriological nature was proved later. Now it is determined that this disease is widely spread in all the countries. The most cases are registered in the warm season. The elderly man suffering from different chronic diseases or alcoholics who use immunedepressors and smoke a lot fall ill more frequently. The disease takes a course of severe progressive abscedic pneumonia with parapneumonic pleuritis and affection of the parenchimal organs.

Ornitosis and Q-fever are diseases which must be no often differentiated from influenza complicated with pneumonia. Both diseases are not accompanied with affection of the upper respiratory tract but have an expressed intoxication and prolonged fever hepatolienal syndrome and atypical affection of the lungs. Well gathered epidemiological anamnesis (contact with birds or their discharge in ornitosis, contact with different animals usage of raw milk and other diary products, usage of cotton brought from endemic regions, etc. in Q-fever) helps to diagnose the disease.

It is necessary to say in conclusion that the differential diagnostics of influenza and its complications in spite of the seeming simplicity is actually quite difficult. The basis of diagnostics and differential diagnostics should be a careful analysis of clinical epidemiological data which can allow either to suspect influenza or doubt this diagnosis. The most simple clinical investigation of blood, urine and spinal liquor help in the diagnostics. The serological, bacteriological and immunefluorescent methods of investigation are of primary importance.

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Diagnosis

The virusological methods of diagnostics are used to isolate and identify the influenza virus. As a rule these methods are used to find out the nature of the outbreaks but not the sporadic cases of the disease because they are very laborious and less sensitive as compared with the serologic methods.

The infection of the chicken embryos is universal method of the primary isolation and cultivation of influenza virus. This method is more accessible and sensitive than the infection of the laboratory animals. It is performed by insertion of the virus containing material in the amniotic or allantoic cavities and causes the infection of organs and tissues of the chicken embryo with the following accumulation of the influenza viruses in the embryos liquid. The presence of the influenza virus in the allantoic or amniotic liquid is stated by the hemagglutination reaction (GAR). The simultaneous erythrocytes of the chicken an guinea pig testifies in favor of the viruses A and B presence, various the agglutination of only chicken erythrocytes suggests the presence of virus type C. In case of the erythrocyte agglutination absence it is necessary to make 2-3 additional passages by the way of embryos infection with the mixture of allantoic and amniotic liquid from the previous passage. In case of the negative results of GAR after the passages the investigation of the material is finished.

The methods of the influenza virus isolation in the tissue culture are preliminary and demand the following pathogen cultivation on the chicken embryo. The trypsineted cultures from the kidneys of monkeys and human foetus are the most suitable for the influenza virus isolation.

The serological diagnostics of influenza ensures an accurate determination of etiology by the way of revealing the quantitative growth of specific antibodies in the disease dynamics in blood. The serological diagnostics is especially important in case of the atypical or symptomless course of the influenza infection. In such cases the discovery of antiinfluenza antibodies in the blood of the examined people in the dynamics of the increasing concentration independently of virusological investigation is the only truthful of the influenza virus participation in the development of the disease and its cooperation with the human organism. Among the methods of influenza serological diagnostic the reaction of hemagglutination inhibition (RHAI) and the reaction of complement banding (CB) is the most widely spread.

The immunefluorescent method is recommended by WHO as one of the reliable means of quick deciphering of the etiology of acute respiratory diseases. The sorting of patients with acute respiratory diseases is done on the bases of the immunefluorescent method data, it is especially important for the prevention of the cross infection of children of an early age. Being widely used this method is an important and reliable means of control of the etiological structure of the acute respiratory diseases in different periods according to the epidemic situation. The essence of the immunefluorescent method is in specific reaction of antigen-antibody which reveal the presence of viral antigens in the cells by the way of joining antibodies to them, the antibodies are connected with the fluorescent mark, which lights in the ultraviolet rays.

Treatment.

Among antiviral agents which are indicated at influenza type A, Remantadin is recommended in such doses: at 1-st day  0,1 gr. 3 times per day, at 2-nd and 3-rd day  0,1 gr. 2 times, at 4-th   0,1 gr after meal.

The positive effect at influenza of type A and B is at using Adampromin. Synthetic preparation Ribamidil (Ribavirin) has positive influence on viruses of grippe of types A and B which is indicated at a daily dose 0,3 – 0,6 gr. during 5 days, however in clinical conditions rather inconsistent data are received. Perspective combined indication of Ribavirin with Remantadin or Adampromin as medical aerosols is represented. Adampromin influences on viruses of an influenza A and B. Similar antiviral property have Midantan, Deitiforin, Arbidole.

As agent of a choice can be a human leukocytic interferon:  3 – 5 drops in each nasal meatus through 1 – 2 hours not less than 5 times per day during 2 – 3 days or as aerosole with the same frequency.  Treatment of virus rhinitis includes:– Unguent of Oxolini, grease a mucosa of nose 2 – 3 times per day 3 – 4 days. The preparation is indicated at herpetic superinfection, however its efficiency is low. The specified antiviral agents should be applied in the first days of disease, later they are not effective.

To decrease a body temperature, and to reduce a headache and muscular pain   Analgin, Ascofen, Upsarin with vitamin C, Eferalgan, Paracetamol are indicated. As a preparation of a choice you can use noarcotic analgetic Amison, rendering analgetic, anti-inflammatory, antipyretic and inferonogenic action.  The fever is the major adaptive and protective reaction of organism, induces synthesis of an endogenic interferon. Antipyretic preparations are indicated only at a hyperpyrexia and expressed cerebral and cardiovascular disorders in adegnote dose to lower a body temperature on 1 – 1,5 C.

As the stimulation of endogenic interferonotransformation apply Amixin  0,125 – 0,25 gr. per day for 2 days, then on 0,125 gr. in 48 hours for one week or in the first 2 – 3 days prescribe Mefanam acid 0,5 gr. 2 times per day. For patients Polyvitamines, Ascorutin are indicated. At excruciating tussis indicate Codein phosphat, Codterpin, tablets against tussis, at labored nasal respiration – Halazolin, Farmasolin or Naphthyzin, Efedrin hydrochloride, Pinosol, at exaltation and disorders of sleeping – mixture of Behterev, Fenobarbitalum for the night.

In serious cases of influenza and the weakened patient, with  indicated specified agents, infuse antiinfluenza  donor immunoglobulin 3 ml. (I.M.) unitary, sometimes repeatedly in 6 – 12 hours.

In connection with the expressed toxicosis infuse Reopolyglucin,  solution of Albumin,  isotonic solution of  Sodium chloride, 5 % a solution of glucose (I.V.). For prevention of hypertension in a small circle of a circulation and a fluid lungs, it is necessary to infuse no more than 500 – 800 ml of liquids slowly and simultaneously to use diuretic preparations – Furosemid, Diacarb, Etacrinic acid. Appoint Corglykon, Sulfocamphocain,  Euphyllin, inhalations of Oxygen or Carbogen.

Patients with especially serious (hypertoxical) form of influenza should be treated in departament of intensive treatment.  Antiinfluenza gamma-globulin or a serumal polyglobulin indicate  3 – 6 ml. in 4 – 6 hours (in  muscle or even in  vein). Infuse (I.V.) admixture of the following structure: blood plasma –150- 200ml; solution of glucose  40 %  – 20 ml, Mesaton 1 % or Noradrenalin 0,2 %  1 ml.; strophanthin 0,05 %  or Corglykon 0,06 %  0,5- 1 ml.; Furosemid (Lasix) 40 -80 mg; Hydrocortizon  250- 400 mg; Euphyllin 2,4 %  1 ml; ascorbic acid solution 5 %  5- 10 ml; calcy chlorid solution 10 %   10 ml; polyglobulin-3 ml. At disorders of cardiac activity use- Corglykon or  Strophanthin. At increase of hypoxia and  fluid of lungs prescribe to inhale Oxygen-alcohol mixture on extremity impose venous garrots, apply diuretic preparations.

In case of development of acute edema and  brain swelling in a vein infuse Mannit (or. Mannitole, Furosemid (or. Lasix), preparations of a potassium, glucocorticoids.

Widely use tinctura of the herbs, with sudorific, anti-inflammatory, soothing, spasmolytic, expectorating and antimicrobial properties.

The collecting  №1 consists of- root of Altea medicinal (2 parts), buds of a birch white (1 part), flowers of elder black (1 part), a rhizome with roots of Inula (1 part), a grass of St.-John’s wort (7 parts), berries and leaves of a raspberry ordinary (2 parts), a leaves of mint peppery (2 parts),  buds of a pine ordinary (2 parts), a grass of a sage medicinal (2 parts), leaves of Eucaliptus (2 parts);

the collecting №2 consists of- root sweetflag (1 part),  buds of a birch white (2 parts), herbs of Origana ordinary (3 parts), a root of Valeriana medicinal (1 part), a herb of St.-John’s wort  (3 parts),  leaves of Viburn ordinary (2 parts), a seed of flax sowing (2 parts), a herb of a yarrow ordinary (2 parts), fetuses of fennel garden (2 parts). It is necessary to fill 4 or 6 dining spoons of the collecting in a thermos (0,7 – 1 l.) to fill up to top with abrupt boiled water, to sustain 3- 4 houres and to drink all within day in 3 – 4 receptions. Course of treatment by such shock doses lusts 3 – 5 days.  The next days use usual doses- making 2 – 3 dining  spoons of an admixture 0,5 l. of boiled water. Among other medicinal herbs for preparation tinctures it is possible to use leaves of Fragarias wood, Tussilagoes farfara, flowers of Camomily Calendulaes, an elder black, lindens. For inhalations use broths of leaves of sage, Eucalyptus, grasses of thyme, pine buds, buds and young branches currants, birches, raspberries, a root of willow-leaf inula, better acidified- then rinse a mouth, a throat and wash out a nose. Revaitl Garlick Pearls  indicate to rise immunity . The heating of a thorax with the help of Sinapismuses, mustard wrappings or pepper Emplastr is prescribed. The same agents put to a plantar surface of the feet and shins.

Antibiotics at an influenza are indicated in following cases: 1) at serious current of disease (the hypertoxical form with encephalitis if disease begins with a pneumonia); 2) to children of the first 2 years of the life, the pregnant,to weaken patients, to persons of elderly and senile age; 3) at bacterial complications; 4) at accompanying chronic diseases of inflammatory character which may become aggravated at influenza. In other cases antibiotics contrindicative, as they strengthen allergization of organism and enlarge frequency of various complications.

Treatment of bacterial complications is necessary to start, before getting results of bacterial inoculation and definitions of sensitivity on antibiotics of the allocated microflora. At the pneumonia indicate benzylpenicillin or one of semisynthetic Penicillins. At a hypersensibility of organism to these preparations use Erythromicin, Oleandomycin or Doxycyclin. At ambulatory treatment also frequently indicate one of the combined preparations – Oletetrin, Tetraolen, and at more serious current of pneumonia – Vancomycin, Tienam and antiinfluenza a gamma-globulin or a polyglobulin. The expressed effect is spotted at a combination of preparations of Tetracyclines or Cefalosporines with semisynthetic Penicillins and Gentamicin, infused parenterally. At unsuccessful treatment after 5 – 7 days choose antibiotic in view of sensitivity of microflora of sputum. Alternative preparations may be a Fusidin – Natry, Bactrim, Nitroxolin.

    At serious bacterial complications of influenza apply Macrolides of II – III generations: Sumamed, Claritromicin, Cefalosporines of III -IV generations – Cefotaxim, Cefoperason, Cedex, Cefpirom, combinations of Cefalosporines and Penicillins with inhibitors of β-lactamazes ( acid Clavulanic, Sulbactam, Tasobactam) and Aminoglicosides. Preparations of a choice may be Ftorhinolones – Ofloxacin, Ciprofloxacin, Pefloxacin and others, which have high antibacterial activity and wide spectrum of action, including influence on polyresistant of Gram-negative and Gram-positive bacteries.

 Use  antitussive (Glaucini hydrochloride, Libexin, Tusuprex), expectorating ( terpin hydrate, Natrii benzoic, broth of a herb of Termopsis, a root of althaea, mucolytic (Acetylcystein, Bronchoclar, Bromhexin, Ambroxole, Lasolvan, Fluditec) agents, physical methods of treatment.

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http://emedicine.medscape.com/article/219557-medication#showall

ADENOVIRAL INFECTION

Definition

Adenoviral infection is a disease developing mainly in children and having the symptoms of the mucus affection of the respiratory tract, eyes. intestines as well as lymphoid tissue.

Historic Reference

The pathogens of the adenoviral diseases were first isolated in 1953 by W. Rowe and his staff from the tissues of the surgically extracted glands and adenoids. The belonging of the isolated viruses to the respiratory infection pathogens was established in 1954 when M. R. Hilleman and J. H. Werner discovered the increase of the neutralizing complement binding to them antibodies in the blood serum. In April of 1954 F. Neva and J. F. Enders isolated a similar virus from the excrement of a two-year-old child who had a fever accompanied by conjunctivitis, pharyngitis and the increase of the neck and groin lymph nodes. A year later R. J. Huebner and W. P. Rowe reported on the isolation of more than 100 cultures of viruses from the nasopharynx, conjunctiva and excrement of the patients who had different forms of the acute febrile diseases of the respiratory tract.

In 1956 the commission at the International committee of the nomenclatures that studied viruses named the isolated viruses “Adenoviruses” as they had first been isolated from the adenoids and the diseases caused by them got the name “adenoviral diseases”.

http://www.cdc.gov/adenovirus/about/overview.html

In 1962 J. Trentin and his co-author R. Huebner together with their co-authors made some experiments on the newbom hamsters that showed that the adenoviruses were oncologically active.

The adenoviruses constitute a family of Adenoviridae including two clans: Mastadenovirus (M) (mammal) of more than 90 kinds and Aviadenovirus (A) (birds) – 18 kinds. The gene of the adenoviruses is a lineal double spiral DNA. They are thermolabile, get destroyed at 56° C in 30 minutes, stable to pH 5-9. They can be preserved in the frozen form. They can be lyophilized without losing the infectious titer (Fig. 2).

 

Fig. 2. Adenovirus

Epidemiology

The adenoviral diseases are registered everywhere all the year round, more often in the cold seasons. The natural reservoir of the adenoviruses for humans is a human. The infection is spread by both the people with the clinically expressed disease and virus carriers. The adenoviruses are excreted from the respiratory tract till the 25^th day of the disease, and from excrement for two months. Though the main way of the infection transmission is an airborne one, an alimentary way cannot be excluded. In the period of the epidemic spread the adenoviruses can also be isolated from the sewage. The diseases can be observed both in the form of the epidemic outbreaks and sporadic cases. The epidemic process during the outbreaks develops slowly. At first the single cases of the disease and then a more rapid growth. Taking into account the meaning of the separate serotypes in the pathology and the peculiarities of the epidemic process the adenoviruses are divided into epidemic, latent and a group which role in the pathology is unclear. The adenoviruses of the latent group also cause acute diseases but in this case there is a less intensive coverage of people at outbreaks, a higher per cent of the latent infection and a mild course are observed.

http://virus.stanford.edu/adeno/adeno.html

Pathogenesis

The adenoviruses usually affect different organs and tissues: the respiratory tract – eyes, lymphoid tissues, intestines and urinary bladder.

The upper parts of the respiratory tract and conjunctivas are the most frequent entrance gates. The virus penetrates the lower parts from the upper part through the bronchial paths and causes atypical pneumonia in adults and children. The virus intensively reproduced in the parenchyma of the lungy and in the cells of the upper respiratory tract. Virusemia is one of the stages of the adenoviral infection. Because of virusemia the virus can penetrate not only the lower respiratory tract but also other organs and tissues by a hematogenic way. In the diseases connected with the adenoviruses of the academic type, virusemia is observed in the acute period from the 1^st to the 8th day. In the latent type cases the period of virusemia lasts up to 2-3 weeks.

The viruses are supposed to affect the endothelium of the vessels and thus cause the exudative type of affection, inclination towards the prolapse of fibrin, necrotic changes in the mucus membrane (exudative pharyngitis, tonsillitis. film conjunctivitis).

Irrespective of the fact that an adenoviral disease has only respiratory or respiratory and intestines symptoms the reproduction of the adenoviruses is observed in the small intestine for longer periods of time (10 days and longer) than in the respiratory tract.

An association of the adenoviruses with the immune deficiency conditions has been described. They were isolated from the urine and excrements of the AIDS patients as well as from the urine of the patients who were ill with other immune deficiency illnesses.

Lymphadenopathy has such symptoms as the increase of the tonsils, periphery lymph nodes, liver, spleen, tracheobronchial. bronchopulmonal and mesenteric nodes.

http://emedicine.medscape.com/article/211738-overview#showall

Clinical manifestations

The disease caused by the adenoviruses is characterized by the polymorphism of the clinical manifestations, that do not develop simultaneously. There are symptoms of the affection of the respiratory tract, eyes, intestines mucous membrane, the disease is accompanied by a prolonged fever and a moderately expressed intoxication. The incubation period lasts 5-7 days with the fluctuations from 4 to 12 days. The adenoviral infection is mainly characterized by a gradual development of the disease with the accumulation of the clinical symptoms, the replacement of some symptoms by others and the prevalence of the local symptoms over the general ones. Besides, an acute onset of the disease is also possible. As a rule the expressed catarrhal symptoms with a labored nasal breathing come to the foreground. The intoxication is expressed by flabbiness, adynamia, the appetite worsening, moderate and inconstant headaches, sometimes vomiting. The rise of the temperature is usually gradual, in the beginning 37.2°C. on the following days – 38° C and sometimes higher. The duration of the fever is 5-7 days less often – up to 12 days.

The acute respiratory disease is the most frequent clinical manifestation. There are usually no pathognomonic symptoms. In the beginning its diagnostics is considerably difficult, especially, in the first cases because they do not practically differ from catarrh caused by different other pathogens. The onset can be acute or gradual. Already on the first day there is a labored nasal breathing, and on the second-third day an abundant serous or serous-mucous discharge. There develops hyperemia of the nasopharynx mucous membrane, edema of the uvula, hyperplasia of the lymphoid tissue, especially, on the back wall of the throat. There is sometimes a vesicular rash on the mucous membrane of the mouth cavity. The submandibular lymph nodes and the ones on the back of the neck are enlarged. The cough is usually dry, it becomes rough, barking when laryngitis develops. sometimes the voice becomes hoarse, but there is no aphonia. In contrast to influenza croup develops in the first hours of the disease. The physical manifestations in the lungs are absent or they are poorly expressed.

Acute Pharyngitis. It is usually in the cold season of the year that the disease is observed, the general condition often remains satisfactory. The main complaint is a pain in the throat at swallowing. Moderate hyperemia of the airfoils, back wall of the throat with hyperplasia of the lyinphoid tissue can be noticed during the throat examination. The mucous membrane of the throat, airfoils, uvula, tonsils is loosened, edematic. On the surface of the tonsils there is a thin whitish patch in the form of dots which covers the tonsils. The exudate often spreads beyond the borders of the airfoils to the soft palate, back wall of the throat. The patches disappear during 5-6 days, but the edema of the mucous membranes of the throat and rhinitis usually remain longer. At the same time the peripheral lymph nodes are often enlarged. The cough is frequent, but not constant, it is moist, less often dry.

Pharyngoconjunctival  fever is the most typical clinical variant of the adenoviral infection. The term “pharyngoconjunctival fever” (FCF) was proposed by J. A. Bell and his co-authors (1965) while describing an outburst in the children’s summer camp. They also most fully described the clinical form characterized by the triad: fever, pharyngitis with the enlargement of the lymph nodes and conjunctivitis. As a rule the disease starts with the increase of the temperature which often increases up to 39-40°C and remains for 2-10 days (5-6 days on the average). There is a lytic temperature decrease. The main complaints of the patients are redness and uncomfortable sensation in the eyes, watery eyes. affection of the throat, headache. Somnolence and malaise often develop at the end of the feverish condition. Nausea, vomiting, diarrhea and nasal bleeding are observed very rarely. The bone-muscle aches and weakness are often observed in adults. During the throat examination the hyperemia of the back wall of the throat and lymphatic toll ides on it is observed. The submaxillary lymph nodes are often enlarged even it there is no pain in the throat. The disease is accompanied by the one-side nonpuruleiit follicular conjunctivitis, which remains from several days to three weeks and is manifested by the injection of the eye and eyelid vessels. The enlargement of the parotid lymph nodes is sometimes observed. There is no photophobia and pain in the eyes. The iris of the eye and cornea are usually not involved in the process. The exudale is almost always serous. The clinical symptoms (fever, pharyngitis and conjunctivitis) are manifested in different combinations. The pharyngoconjunctival fever in the form of sporadic cases or outbursts is registered in different countries.

Eye Affection. The intensely expressed inflammation of the conjunctiva with bright hyperemia and scarce discharge is a peculiarity of adenoviral conjunctivitis. The inflamed mucous membrane of the conjunctiva looks like a “conflagration without a fire”. Unlike in conjunctivitis of another etiology only the lower eyelid is usually affected. In the beginning the inflammatory process in the eye develops only on one side and only later the second eye gets involved in the process, but the changes in it are less expressed. There are such forms of the eye affection as catarrhal follicular. membranous conjunctivitis and keratoconjunctivitis. The last ones usually develop in adults; a long recurring course is typical of them.

In case of the catarrhal form hyperemia. tissue infiltration, edema of the eyelids and conjunctiva are observed. The edema and the infiltration of the tissues usually disappear in 2-5 days. but the hyperemia of the conjunctiva remains up to three weeks, sometimes – up to a month.

In case of the follicular form of conjunctivitis along with conjunctiva infiltration and edema of the eyelids there is abundant eruption of the large follicles on the conjunctiva. There is no discharge or it is scarce. One third of the patients have a hemorrhage into the sclera of the eyeball. The hemorrhage dissolves slowly, during 7-9 days. and then during 3-4 days a vessels’ netting “sclera injection'” can be observed. Sometimes the hemorrhages are so large that the eye looks like a rabbit’s one (Fig.3).

Fig.3. Conjunctivitis

In case of membranous conjunctivitis the tissue infiltration, eyelid edema are much more expressed (often a patient cannot even open the eye) than in catarrhal or follicular forms, and the edema of the eyelids is soft in contrast to the diphtheritic one. The hemorrhages into the conjunctiva and sclera of the eye are more massive. The gray dense films appear on the 4-6 day of the disease. The bleeding surface remains after their removal. The discharge is scanty, very often there is sanioserous discharge. Parents say that “the child cries with bloody tears”.

In case of keratoconjunctivitis the disease has an acute onset and is manifested by hyperemia and the conjunctiva edema. On the 2-3 rd day together with the eyelid edema, redness of the eyeball conjunctiva, lachrymal muscle and semilunar fold. Hemorrhages appear on the eyelid conjunctiva and the hypodermic fold. In some cases the films appear on the eyelid conjunctiva. The abundant eruption on the eyelid conjunctiva and transitional folds of the superficial follicles is very typical. The discharge is usually scanty. The enlargement and tenderness of the parotid and sometimes submandibular lymph nodes are important diagnostic symptoms (Fig.4).

 

Fig.4. Keratoconjunctivitis

The typical changes in the cornea appear on the 7-14th day of the disease. Their appearance often coincides with the disappearing of the inflammatory processes in the conjunctiva. On the cornea, usually in the center, in the pupil zone. there are delicate subepithelial round infiltrates, which do not tend to ulceration. The disease is sometimes accompanied by the temperature increase. Quite often the patients complain of a headache and general malaise. A patient considers the dimness of the cornea to be a foreign body. photophobia. and vision disorder. In half of the patients only one eye is affected, but in some time (7-10 days) the second eye can get involved in the process. The disease lasts from 8-10 days to 6-7 weeks. The foci of dimness on the cornea dissolve slowly, during 3 months. In some cases the dimness remains for a long time and causes the vision worsening.

 Pneumonia. Among different forms of the adenoviral diseases pneumonia causes the greatest alarm, especially, in the children of the young age. Clinically the symptoms of the pneumonia in case of the adenoviral infection are expressed quite distinctly. The disease has an acute onset with the temperature increase up to 38-39°C; the temperature curve is usually irregular, with oscillations, quite often the fever period has a lingering character up to 20 days and longer. The temperature reaction is not expressed or absent in the children of the first months. Pneumonia is accompanied by the expressed catarrhal manifeslations in the upper respiratory tract. The fauces mucous membrane is hyperemi, edematic, the tonsils are enlarged and in some cases they are covered with whitish fur. The nasal discharge is abundant. The discharge is mucous or mucopurulent. The cough is painful, often excruciating, dry or with the discharge of the mucopurulent sputum. During the first days of the disease the physical changes in the lungs may not be found, they usually develop later. From the 3-4th day of the disease along with the shortening of the resonance with the tympanic inflection there is a big amount of dry and mixed moist rale. The rale can disappear, and then come back again. Sometimes an asthmatic component joins these manifestations. The massive affection of the lung tissues is revealed during the X-ray examination. The inflammatory foci flow together. they dissolve slowly. A tendency to relapses, exacerbation and a slow reparation of the inflammatory process in the lungs are characteristic of adenoviral pneumonia. A severe course of pneumonia with an unfavorable outcome is usually observed in the children of the early age, and in other patients who are weakened by previous diseases or accompanied diseases. Pleuritis and abscesses can complicate pneumonia, but it occurs comparatively rarely.

The changes of some inner organs and systems, which are typical of the adenoviral disease (lymphadenopathy, hepalosplenic syndrome, changes in the cardiovascular, nervous system, hematological changes, etc.). are more expressed in case of pneumonia and occur more often comparing with the uncomplicated course of the disease. Sometimes pneumonia is accompanied by conjunctivitis which is characteristic of the adenoviral disease, that helps in the etiologic diagnostics.

 

 

 

Diagnosis and Differential Diagnosis

 The problems in the differential diagnostics of the diseases which form this group are due to the fact that different viruses can cause similar clinical syndromes and first of all the syndrome of the acute disease of the respirator, tract.

The differential diagnostics is possible only in case of the typical course of the disease during the clinical recognition of the nosologic forms taking into consideration the peculiarities of the location of the pathological process, the degree of the toxicosis, the presence and expressiveness of the catarrhal manifestations as well as changes in other organs and systems.

Times, in contrast to influenza in the adenoviral diseases the local limited outbreaks are registered, the incubation period in the infected patients is longer, the catarrhal manifestations with an abundant discharge are considerably expressed, there are typical changes in the fauces, the lymph nodes, liver and spleen are enlarged, relapses occur later.

In contrast to paragrippe the onset of the adenoviral diseases is often acute. the exudative component is more expressed, there is lymphoadenopathy. one-side conjunctivitis.

The clinical diagnostics of the RS infection is based on the primary affection of the lower parts of the respiratory tract, quite often with an asthmatic component and respiratory insufficiency. The changes in the upper parts are less expressed.

The confirmation of the diagnosis is based on the laboratory investigations. The collection of the material and the investigation methods are the same as in case of other viral infections of the respirators tract.

Treatment.

Treatment will carry out in view of gravity of current and the clinical form of disease. Localy use the etiotropic  preparation Desoxyribonucleasa which is instilated into  conjunctival bag and nasal courses as the solution. Apply also a solution of Oxolin, Oxolin Unguent, or Florenal for pawning edges of blepharons and for greasing mucosa of nose. As agent of a choice use solution of  human interferon as inhalations, dispersion or drops in a nose through every 1 – 2 houres during 2 – 3 days. Efficiency of treatment above, than earlier it is begun. Among inductores of interferon and imunomodulatores indicate amixin, amizin, cycloferon, proteflazid, erbisol. At serious forms of disease use human placental or serumal immunoglobulin (3 – 6 ml. unitary), at absence of effect give repeatedly in 6 – 8 houres or oext day. According to the indications apply infusions of 5 % of  solution of a glucose with ascorbic acid. Reopolyglucin,  salt solutions, humidified Oxygen are used through a nasal catheter.

    Recommend a hot drinks of tinctura of Raspberries, Lime color, flowers of a black Elder, tea with lemon. For inhalations use warm broths of leaves of eucalypt,  sage, pine buds, grasses of thyme, buds of a birch (separately or in admixture), for a gargle of pharynx and an oral cavity give broths of flowers Chamomiles, Calendula, grasses of a Yarrow, Sage.

In case of rhinitis  we instill into nose vasoconstrictive preparations,such as: naphthyzin ,  ephedrin hydrochloride, pharmasolin. For cupping of inflammatory process apply into nasopharynx Faringosept or Falimint. Among others agents recommend Pectusin or Terpin hydrate, Ascorutin,Calci of gluconate, Methyluracil, and also Diazolinum, Suprastin, Tavegil, Gismanal, Zestra, Loratidin, Alegra, Telfast.

In case of bacterial complications antibiotics and others chemotherapeutic agents are indicated in view of kind of the originator and its medicinal sensitivity. Use benzylpenicillin sodic salt, Ampicillin sodic salt, Carbapenicilin dinatri salt, Ampiox, Erythromycin, Oleandomycin phosphas or Doxycyclin hydrochloride, Cefalosporines (Cefazolin, Cefotaxim, Ceftriaxon).http://emedicine.medscape.com/article/211738-medication#showall

http://intranet.tdmu.edu.ua/data/books/And–INF.pdf