Smallpox: epidemiology, pathogenesis, forms

Smallpox (Latin variola, variola major) is an anthroponous, especially dangerous viral infection with an aerosol mechanism of transmission of the pathogen, characterized by severe intoxication, a two-wave fever, and vesicular-pustular exanthema and enanthema.

[1], [2], [3], [4], [5], [6], [7],

Epidemiology of smallpox

The source and reservoir of the pathogen is a patient from the last days of the incubation period to complete recovery (the maximum danger is presented by patients from the 3rd to 8th day of the disease).

The mechanism of infection of smallpox is aerosol. Transmission of the pathogen occurs by airborne or airborne dust. Transfer factors: virus-infected air, dust, underwear and bedding. Possible infection through conjunctiva, damaged skin; in pregnant women - transplacental infection of the fetus. The epidemic danger is also represented by corpses of people who died from smallpox. The natural susceptibility of people reaches 95%. After the transferred disease, as a rule, stable immunity develops, but it is possible and repeated disease (in 0.1-1% of patients who have recovered). Smallpox is a highly contagious disease. A high incidence rate with epidemic character and cyclical upturns was recorded every 6-8 years in countries of Africa, South America and Asia. Children were more often infected at the age of 1-5 years. In endemic countries, the incidence rate was noted in the winter-spring period.

On October 26, 1977, the last case of smallpox was registered. In 1980, WHO certified the eradication of smallpox around the world. The WHO Committee on Orthopoxviral Infections in 1990 recommended, as an exception, vaccination to researchers working with pathogenic orthopoxviruses (including variola virus) in specialized laboratories and in smallpox smallpox pockets.

When detecting patients with natural smallpox or when suspected of a disease, establish regime-restrictive measures (quarantine) in full. Contact persons are isolated in a specialized observatory for 14 days. For emergency prophylaxis of smallpox, metisazone and ribavirin (virazole) are used in therapeutic doses with simultaneous application of smallpox vaccine.

[8], [9], [10], [11], [12], [13],

What causes smallpox?

Smallpox is caused by a large DNA-containing virus Orthopoxvirus variola of the family Poxviridae of the genus Orthopoxvirus. The dimensions of brick-like virions are 250-300x200x250 nm. Virion has a complex structure. Outside, the shell is located, which is formed when you leave the cell. The outer lipoprotein membrane, which includes glycoproteins, is collected in the cytoplasm around the core. The nucleoprotein complex, enclosed in the internal membrane, consists of proteins and one double-stranded linear DNA molecule with covalently closed ends.

The variola virus has four major antigens: an early ES antigen, which is formed before the synthesis of viral DNA begins; rhodospecific LS-antigen. Related to non-structural polypeptides; group-specific nucleoprotein NP-antigen (produces the formation of virus-neutralizing antibodies), consisting of a number of structural polypeptides; species-specific hemagglutinin - glycoprotein. Localized in the lipoprotein coat of the virion.

The main biological properties that are important in the laboratory diagnosis of smallpox:

• when cytoplasm of epithelial cells is multiplied, specific cytoplasmic inclusions are formed: B inclusions (virosomes) or Gvarnieri bodies;
• on the chorion-allantoic membrane of chick embryos, the virus multiplies with the formation of clearly limited monomorphic dome-shaped smallpoxes;
• has moderate hemagglutination activity;
• causes a cytopathic effect and a phenomenon of haemadsorption in cells of the transplanted kidney line of a pig embryo.

The causative agent of smallpox is highly resistant to environmental factors. In small pox at room temperature, the virus persists up to 17 months; at a temperature of -20 ° C - 26 years (observation period), in a dry environment at 100 ° C inactivated after 10-15 minutes, at 60 ° C - after 1 hour. Bends under the action of 1-2% chloramine solution after 30 minutes, 3% solution of phenol - after 2 hours.

The pathogenesis of smallpox

When the aerosol mechanism of infection affects cells of the mucous membrane of the nasopharynx, trachea, bronchi and alveoli. Within 2-3 days the virus accumulates in the lungs and penetrates into the regional lymph nodes, where it actively replicates. On the lymphatic and bloodways (primary viremia), it enters the spleen, liver and free macrophages of the lymphatic system, in which it multiplies. After 10 days, secondary viremia develops. Infected skin cells, kidneys, central nervous system, other internal organs and appear the first signs of the disease. Typical for the virus, tropism to the cells of the skin and mucous membranes leads to the development of typical poppy elements. Changes in the dystrophic character develop in the parenchymal organs. With hemorrhagic smallpox, the vessels are affected with the development of ICE.

Symptoms of smallpox

The incubation period of smallpox lasts an average of 10-14 days (from 5 to 24 days). With varioloid - 15-17 days, with alastrime - 16-20 days.

The course of smallpox is divided into four periods: prodromal (2-4th day), rash (4-5 days), suppuration (7-10 days) and reconvalescence (30-40 days). In the prodromal period, the temperature suddenly increases with fever to 39-40 C, the following symptoms of smallpox occur: severe headache, myalgia, pain in the lumbar region and abdomen, nausea, sometimes vomiting. Some patients on 2-3 days in the region of the femoral triangle of Simon and thoracic triangles appear typical symptoms of smallpox: korepodobnaya or scarlet feverish prodromal rash (rose rack). With a 3-4-day sickness against the background of a drop in temperature, a true rash appears, indicating the beginning of the rash period. The rash is spread centrifugally: the face → trunk → extremities. Elements of the rash undergo a characteristic evolution: macula (pink spot) → papule → vesicle (multi-chambered vesicles with umbilicus in the center, surrounded by a zone of hyperemia) → pustules → crusts. On one site the rash is always monomorphic. On the face and extremities, including the palmar and plantar surfaces, the exanthema elements are larger. Enanthema is characterized by the rapid transformation of vesicles in erosion and ulcers, which is accompanied by painfulness during chewing, swallowing and urination. From 7-9 days, during the period of suppuration, vesicles become pustules. The temperature rises sharply, the phenomena of intoxication increase.

By the 10th and 14th days, the pustules begin to dry out and turn into yellowish-brown, then black crusts, which is accompanied by an excruciating cutaneous itching. By the 30-40th day of the disease, in the period of convalescence, peeling occurs, sometimes lamellar, and the crusts fall away with the formation of scars of a radiant structure of pink color, subsequently pale, giving the skin a rough appearance.

Classification of smallpox

There are several clinical classifications of smallpox. The most widespread classification was Rao (1972), recognized by WHO committees, and the classification according to the severity of clinical forms.

Classification of the clinical types of smallpox (variola major) with the main features of the flow according to Rao (1972)

Type (form)	Subtypes (variant)	Clinical Features	Mortality,%
			In unvaccinated	In vaccinated
Usual	Drainage	Drain rash on the face and extensor surfaces of the limbs, discrete - on other parts of the body	62.0	26.3
	Sleuth	Drain rash on the face and discrete - on the body and limbs	37.0	84
	Discrete	Spines scattered throughout the body Between them - unchanged skin	9.3	0.7
Modified (varioloid)	Drainage Sleuth Discrete	It is characterized by an accelerated course and the absence of intoxication phenomena	0	0
Smallpox without rash		Against the background of fever and prodromal symptoms, there is no smallpox rash. The diagnosis is confirmed serologically	0	0
Flat	Drainage Sleuth Discrete	Flat elements of the rash	96.5	66.7
Hemorrhagic	Early	Hemorrhages on the skin and mucous membranes already in the prodromal stage	100.0	100.0
	Late	Hemorrhages on the skin and mucous membranes after the onset of rash	96.8	89.8

Classification by severity of clinical forms of smallpox with the main features of the flow

The form	Degree of severity	Clinical Features
"Big Pox" (Variola major)
Hemorrhagic (Variola haemorrhagica s. Nigra)	Heavy	1 Purple purpura (Purpura variolosa) hemorrhages are noted already in the prodromal period Possible fatal outcome before the onset of rash 2 Hemorrhagic pustuleznaya rash "black pox" (Variola haemorrhagica pustulosa - variola nigra) phenomena of hemorrhagic diathesis occur during the period of suppuration of pustules
Drain (Variola confluens)	Heavy	Elements of the rash merge to form solid bubbles filled with pus
Ordinary (Variola vera)	Medium-heavy	The classical current
Varioloid - smallpox in vaccinated (Variolosis)	Lightweight	In the prodromal period, symptoms are poorly expressed. Subfebrile fever lasts 3-5 days. The period of rashes occurs on the 2nd-4th day of the disease: the macula is transformed into papules and vesicles without the formation of pustules
Smallpox without rash (Variola sine exanthemate)	Light	General intoxication, myalgia headache and pain in the sacrum are mild. Body temperature is subfebrile. The diagnosis is confirmed serologically
Smallpox without temperature (Variola afebnlis)	Lightweight	Symptoms of intoxication are absent. Accelerated current
"Smallpox" (Variola minor)
Alastrim is a smallpox (Alastrim)	Lightweight	In the prodromal period all the symptoms are expressed, but on the third day after the onset of the disease the temperature normalizes and a bubble rash appears, giving the skin the appearance of a lime solution covered with a spray. Pustules are not formed. The second fever wave is absent.

[14], [15], [16], [17], [18], [19]

Complications of smallpox

• Primary: infectious-toxic shock, encephalitis, meningoencephalitis, panophthalmitis.
• Secondary (associated with the attachment of bacterial infection): iritis, keratitis, sepsis, bronchopneumonia, pleurisy, endocarditis, phlegmon, abscesses, etc.

[20], [21], [22], [23], [24], [25], [26], [27], [28], [29]

Mortality

The lethality with classical (usual) natural smallpox and alastrime among the unvaccinated was on average 28% and 2.5%, respectively. With hemorrhagic and flat smallpox, 90-100% of patients died, with a draining smallpox - 40-60%. And with an average - 9.5%. With varioloid, smallpox without rash and smallpox without temperature, no lethal outcomes were recorded.

Diagnosis of smallpox

The diagnosis of smallpox consists in virological examination of scrapings from papules, contents of rash elements, swabs from the mouth, from the nasopharynx spend on chick embryos or sensitive cell cultures with mandatory identification in PH. To identify antigens of the virus in the test material and to detect specific antibodies in blood serum taken at hospitalization and 10-14 days later. Use ELISA.

[30], [31], [32], [33], [34], [35], [36],

Differential diagnosis of smallpox

Differential diagnosis of smallpox is carried out with chicken pox, smallpox monkeys, vesicle rickettsiosis (differs in primary affect and regional lymphadenitis), pemphigus of unclear etiology (Nikolsky's symptom and presence of acantholytic cells in smears-prints). In the prodromal period and with smallpox purpura - with feverish diseases accompanied by a small spot spot or petechial rash (meningococcemia, measles, scarlet fever, hemorrhagic fever).

[37], [38], [39], [40], [41],

Treatment of smallpox

Diet and diet

Patients are hospitalized for 40 days from the onset of the illness. Bed rest (lasts until the crusts fall off). To reduce the itching of the skin, air baths are recommended. Diet - mechanically and chemically sparing (table number 4).

[42], [43], [44],

Medicinal treatment of smallpox

Etiotropic treatment of smallpox:

• metisazon for 0.6 g (children - 10 mg per 1 kg of body weight) 2 times a day for 4-6 days:
• ribavirin (virazol) - 100-200 mg / kg once a day for 5 days;
• antipoietic immunoglobulin - 3-6 ml intramuscularly;
• prevention of secondary bacterial infection - semisynthetic penicillins, macrolides, cephalosporins.

Pathogenetic treatment of smallpox:

• cardiovascular drugs;
• vitamin therapy;
• desensitizing agents;
• Glucose-salt and polionic solutions;
• glucocorticoids.

Symptomatic treatment of smallpox:

• analgesics;
• hypnotics;
• local treatment: oral cavity 1% solution of sodium bicarbonate 5-6 times a day, and before meals - 0.1-0.2 g of benzocaine (anestezina), the eye - 15-20% solution of sulfacyl sodium 3-4 times a day , eyelids - 1% solution of boric acid 4-5 times a day, elements of rash - 3-5% solution of potassium permanganate. During the formation of crusts, 1% menthol ointment is used to reduce the itching.

Dispensary supervision

Not regulated.

What is the prognosis of smallpox?

Smallpox has a different prognosis, which depends on the clinical form of smallpox.