Smallpox: epidemiology, pathogenesis, forms

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

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Epidemiology of smallpox

The source and reservoir of the pathogen is the patient from the last days of the incubation period until complete recovery (patients pose the greatest danger from the 3rd to 8th day of illness).

The mechanism of smallpox infection is aerosol. The pathogen is transmitted by airborne droplets or airborne dust. Transmission factors: air, dust, underwear and bed linen infected with the virus. Infection is possible through the conjunctiva, damaged skin; in pregnant women - transplacental infection of the fetus. Corpses of those who died from smallpox also pose an epidemic danger. The natural susceptibility of people reaches 95%. After the disease, as a rule, persistent immunity develops, but a second disease is also possible (in 0.1-1% of those who have had it). Smallpox is a highly contagious disease. A high level of morbidity with an epidemic nature and cyclical increases every 6-8 years was recorded in countries of Africa, South America and Asia. Children aged 1-5 years were most often infected. In endemic countries, an increase in morbidity was noted in the winter-spring period.

The last case of smallpox was reported on October 26, 1977. In 1980, WHO certified the eradication of smallpox worldwide. In 1990, the WHO Committee on Orthopoxvirus Infections recommended, as an exception, vaccination of researchers working with pathogenic orthopoxviruses (including smallpox virus) in specialized laboratories and in monkeypox outbreaks.

When smallpox patients are identified or when the disease is suspected, restrictive measures (quarantine) are established in full. Contact persons are isolated in a specialized observation department for 14 days. For emergency prevention of smallpox, methisazone and ribavirin (virazol) are used in therapeutic doses with the simultaneous use of smallpox vaccine.

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What causes smallpox?

Smallpox is caused by a large DNA-containing virus Orthopoxvirus variola of the Poxviridae family of the Orthopoxvirus genus. The brick-shaped virions are 250-300x200x250 nm. The virion has a complex structure. On the outside is a membrane that forms when leaving the cell. The outer lipoprotein membrane, which includes glycoproteins, is assembled in the cytoplasm around the core. The nucleoprotein complex, enclosed in the inner membrane, consists of proteins and one molecule of double-stranded linear DNA with covalently closed ends.

The smallpox virus has four main antigens: the early ES antigen, which is formed before the synthesis of viral DNA; the genus-specific LS antigen, which is a non-structural polypeptide; the group-specific nucleoprotein NP antigen (which produces virus-neutralizing antibodies), which consists of a number of structural polypeptides; the species-specific hemagglutinin, a glycoprotein, which is localized in the lipoprotein membrane of the virion.

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

• during reproduction in the cytoplasm of epithelial cells, specific cytoplasmic inclusions are formed - B inclusions (virosomes) or Guarnieri bodies;
• On the chorion-allantoic membrane of chicken embryos, the virus multiplies, forming clearly defined, monomorphic, dome-shaped, white pockmarks;
• has moderate hemagglutinating activity;
• causes cytopathic action and the phenomenon of hemadsorption in the cells of the transplanted line of pig embryo kidneys.

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

Pathogenesis of smallpox

With the aerosol mechanism of infection, the cells of the mucous membrane of the nasopharynx, trachea, bronchi and alveoli are affected. Within 2-3 days, the virus accumulates in the lungs and penetrates into the regional lymph nodes, where it actively replicates. Through the lymphatic and bloodstream (primary viremia), it enters the spleen, liver and free macrophages of the lymphatic system, where it multiplies. After 10 days, secondary viremia develops. The cells of the skin, kidneys, central nervous system, and other internal organs are infected and the first signs of the disease appear. The tropism of the virus for the cells of the skin and mucous membranes leads to the development of typical smallpox elements. Dystrophic changes develop in the parenchymatous organs. In hemorrhagic smallpox, the vessels are affected with the development of DIC.

Symptoms of smallpox

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

The course of smallpox is divided into four periods: prodromal (2-4 days), rash period (4-5 days), suppuration period (7-10 days) and convalescence (30-40 days). During the prodromal period, the temperature suddenly rises to 39-40 C with chills, the following symptoms of smallpox occur: severe headache, myalgia, pain in the lumbar region and abdomen, nausea, and sometimes vomiting. In some patients, on the 2-3 day, typical symptoms of smallpox appear in the area of the femoral triangle of Simon and the thoracic triangles: measles-like or scarlet fever-like prodromal rash (rose rack). From the 3-4 day of the disease, against the background of a decrease in temperature, a true rash appears, indicating the beginning of the rash period. The rash spreads centrifugally: face → torso → limbs. The elements of the rash undergo a characteristic evolution: macula (pink spot) → papule → vesicle (multi-chambered vesicles with an umbilicated depression in the center, surrounded by a hyperemic zone) → pustule → crusts. In one area, the rash is always monomorphic. There are more exanthema elements on the face and extremities, including the palmar and plantar surfaces. Enanthema is characterized by the rapid transformation of vesicles into erosions and ulcers, which is accompanied by pain when chewing, swallowing and urinating. From the 7th to 9th day, during the period of suppuration, vesicles turn into pustules. The temperature rises sharply, and intoxication symptoms increase.

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

Classification of smallpox

There are several clinical classifications of smallpox. The most widely used is the Rao classification (1972), recognized by WHO committees, and the classification by the severity of clinical forms.

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

Type (shape)	Subtypes (variant)	Clinical features	Mortality, %
			In unvaccinated people	In vaccinated people
Normal	Drain	Confluent rash on the face and extensor surfaces of the extremities, discrete - on other parts of the body	62.0	26.3
	Semi-drain	Confluent rash on the face and discrete rash on the body and limbs	37.0	84
	Discrete	The pockmarks are scattered all over the body. Between them is unchanged skin.	9.3	0.7
Modified (varioloid)	Drain Semi-drain Discrete	It is characterized by an accelerated course and the absence of intoxication symptoms.	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	Drain Semi-drain Discrete	Flat rash elements	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 appearance of a rash	96.8	89.8

Classification of severity of clinical forms of smallpox with the main features of the course

Form	Severity	Clinical features
"Great smallpox" (Variola major)
Hemorrhagic (Variola haemorrhagica s. nigra)	Heavy	1 Smallpox purpura (Purpura variolosa) hemorrhages are observed already in the prodromal period. A fatal outcome is possible before the rash appears. 2 Hemorrhagic pustular rash "black smallpox" (Variola haemorrhagica pustulosa - variola nigra) phenomena of hemorrhagic diathesis occur during the period of suppuration of pustules
Plum (Variola confluens)	Heavy	The elements of the rash merge to form continuous blisters filled with pus.
Common (Variola vera)	Medium-heavy	Classical Current
Varioloid - smallpox in vaccinated people (Variolosis)	Easy	In the prodromal period, the symptoms are weakly expressed. Subfebrile fever lasts 3-5 days. The period of rashes occurs on the 2nd-4th day of the disease: macules turn into papules and vesicles without the formation of pustules
Smallpox without rash (Variola sine exanthemate)	Light	General intoxication, headache, myalgia and pain in the sacrum are weakly expressed. Body temperature is subfebrile. The diagnosis is confirmed serologically
Smallpox without fever (Variola afebnlis)	Easy	There are no symptoms of intoxication. Accelerated progression
"Small pox" (Variola minor)
Alastrim - white smallpox (Alastrim)	Easy	In the prodromal period, all symptoms are expressed, but on the 3rd day from the onset of the disease, the temperature normalizes and a vesicular rash appears, giving the skin the appearance of being covered with splashes of lime solution. Pustules do not form. The second feverish wave is absent.

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Complications of smallpox

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

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Mortality

The mortality rate for classic (ordinary) smallpox and alastrim among the unvaccinated averaged 28% and 2.5%, respectively. For hemorrhagic and flat smallpox, 90-100% of patients died, for confluent smallpox - 40-60%, and for moderately severe - 9.5%. No fatal outcomes were recorded for varioloid, smallpox without rash, and smallpox without fever.

Diagnosis of smallpox

Smallpox diagnostics consists of virological examination of papule scrapings, rash contents, mouth smears, and nasopharynx smears using chicken embryos or sensitive cell cultures with mandatory identification in RN. ELISA is used to identify virus antigens in the material being examined and to detect specific antibodies in blood serum taken during hospitalization and 10-14 days later.

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Differential diagnosis of smallpox

Differential diagnostics of smallpox is carried out with chickenpox, monkeypox, vesicular rickettsiosis (characterized by primary affect and regional lymphadenitis), pemphigus of unknown etiology (characterized by Nikolsky's symptom and the presence of acantholytic cells in smears-imprints). In the prodromal period and with smallpox purpura - with febrile diseases accompanied by a small-point spotted or petechial rash (meningococcemia, measles, scarlet fever, hemorrhagic fever).

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Treatment of smallpox

Regime and diet

Patients are hospitalized for 40 days from the onset of the disease. Bed rest (lasts until the crusts fall off). Air baths are recommended to reduce itching of the skin. The diet is mechanically and chemically gentle (table No. 4).

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Drug treatment of smallpox

Etiotropic treatment of smallpox:

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

Pathogenetic treatment of smallpox:

• cardiovascular drugs;
• vitamin therapy;
• desensitizing agents;
• glucose-salt and polyionic solutions;
• glucocorticoids.

Symptomatic treatment of smallpox:

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

Outpatient observation

Not regulated.

What is the prognosis for smallpox?

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