Epidemic Typhus

What is Epidemic Typhus?

Epidemic typhus (Synonyms: lousy typhus, military typhus, typhoid fever, European typhus, prison fever, camp fever; epidemic typhus fever, louse-born typhus, jail fever, famine fever, war fever-English, Flecktyphus kfieber – German; typhus epidemique, typhus exanthematique, typhus historique – French; tifus exantematico, dermotypho – ucn.) – an acute infectious disease characterized by a cyclical course, fever, rose-petechial exanthema, damage to the nervous and cardiovascular systems, preservation of rickettsia in the body of convalescence for many years.

Causes of Epidemic Typhus

The causative agents of epidemic typhus are R. prowazekii, common in all countries of the world, and R. canada, whose circulation is observed in North America. Rickettsia Provacheka is somewhat larger than other rickettsiae, gram-negative, has two antigens: a surface-mounted species-specific (common with the Museum rickettsia) thermostable, soluble antigen of lipoid polysaccharide-protein nature, under it is a species-specific insoluble thermolabile protein-polysaccharide complex. Rickettsia Provacheka quickly die in a humid environment, but they are stored for a long time in the feces of lice and in the dried state. They tolerate low temperatures well, die when heated to 58 ° C in 30 minutes, to 100 ° C in 30 s. They die under the influence of commonly used disinfectants (lysol, phenol, formalin). Highly sensitive to tetracyclines.

The isolation of typhus into an independent nosological form was first made by Russian doctors Y. Shchirovsky (1811), Y. Govorov (1812) and I. Frank (1885). A detailed distinction between typhoid fever and typhus (according to clinical symptoms) was made in England by Murchison (1862) and in Russia by S.P. Botkin (1867). The role of lice in the transmission of typhus was first established by N. F. Gamaleya in 1909. The blood contamination of patients with typhus was proved by the experience of self-infection by O. O. Mochutkovsky (the blood of a patient with typhus was taken on the 10th day of illness, introduced into the skin of the forearm, O.O. Mochutkovsky’s disease occurred on the 18th day after self-infection and proceeded in a severe form). The incidence of typhus increased sharply during wars and national disasters, the number of cases was in the millions. Currently, a high incidence of typhus has persisted only in some developing countries. However, the long-term persistence of rickettsia in patients previously suffering from typhus and the periodic occurrence of relapses in the form of Brill-Zinsser disease does not exclude the possibility of epidemic outbreaks of typhus. This is possible if social conditions worsen (increased population migration, head lice, poor nutrition, etc.).

The source of infection is a sick person, starting from the last 2-3 days of the incubation period and up to the 7-8th day from the moment of normalization of body temperature. After that, although rickettsia can persist for a long time in the body, convalescence is no longer a danger to others. Typhus is transmitted through lice, mainly through clothes, less often through the head. After feeding the patient with blood, the louse becomes contagious after 5-6 days and until the end of life (i.e. 30-40 days). Human infection occurs by rubbing feces of lice into skin lesions (combing). There are known cases of infection by blood transfusion taken from donors in the last days of the incubation period. Rickettsia circulating in North America (R. sapada) is transmitted by ticks.

Pathogenesis during Epidemic Typhus

The gates of infection are minor skin lesions (often scratching), after 5-15 minutes rickettsia penetrate the blood. Rickettsia propagation occurs intracellularly in the vascular endothelium. This leads to swelling and desquamation of endothelial cells. The cells that get into the blood stream are destroyed, and the released rickettsia affect new endothelial cells. The most rapidly growing process of rickettsia breeding occurs in the last days of the incubation period and in the first days of fever. The main form of vascular lesion is warty endocarditis. The process can capture the entire thickness of the vascular wall with segmental or circular necrosis of the vessel wall, which can lead to blockage of the vessel by the resulting thrombus. So there are peculiar typhoid granulomas (Popov’s nodules). With a severe course of the disease, necrotic changes predominate, with a mild – proliferative. Vascular changes are especially pronounced in the central nervous system, which gave reason to IV Davydovsky to consider that each typhus is non-purulent meningoencephalitis. Vascular damage is associated not only with clinical changes on the part of the central nervous system, but also changes in the skin (hyperemia, exanthema), mucous membranes, thromboembolic complications, etc. After suffering from typhus, a rather strong and long-lasting immunity remains. For some convalescents, this is non-sterile immunity, since Prokachek rickettsia can persist for decades in the body of convalescents and, when the body’s defenses are weakened, cause long-term relapses in the form of Brill’s disease.

Symptoms of Epidemic Typhus

The incubation period ranges from 6 to 21 days (usually 12-14 days). In the clinical symptoms of typhus, the initial period is distinguished – from the first signs to the appearance of the rash (4-5 days) and the peak period – until the body temperature drops to normal (lasts 4-8 days from the onset of the rash). It should be emphasized that this is a classic trend. When antibiotics of the tetracycline group are prescribed, after 24-48 hours the body temperature normalizes and other clinical manifestations of the disease disappear. Typhus is characterized by an acute onset, only in some patients in the last 1-2 days of incubation there may be prodromal manifestations in the form of general weakness, fatigue, depression of mood, heaviness in the head, and a slight increase in body temperature is possible by evening (37.1-37 , 3 ° C). However, in most patients, typhus begins acutely with an increase in temperature, which is sometimes accompanied by chilling, weakness, severe headache, and a decrease in appetite. The severity of these signs progressively increases, the headache intensifies and becomes intolerable. A peculiar arousal of patients is early detected (insomnia, irritability, verbosity of responses, hyperesthesia of the sensory organs, etc.). In severe forms, there may be a violation of consciousness.

An objective examination shows an increase in body temperature to 39-40 ° C, the maximum level of body temperature reaches in the first 2-3 days from the onset of the disease. In classical cases (that is, if the disease is not stopped by prescribing antibiotics) on the 4th and 8th day, many patients had incisions in the temperature curve, when for a short time the body temperature drops to a subfebrile level. The duration of fever in such cases often ranges from 12-14 days. When examining patients from the first days of the disease, there is a kind of hyperemia of the skin of the face, neck, upper chest. Scleral vessels are injected (“red eyes on a red face”). Sooner (from the 3rd day), a symptom characteristic of typhus occurs – Chiari-Avtsyn spots. This is a kind of conjunctival rash. Elements of a rash with a diameter of up to 1.5 mm with blurry fuzzy borders are red, pink-red or orange, their number is more often 1-3, but may be more. They are located on the transitional folds of the conjunctiva, often the lower eyelid, on the mucous membrane of the cartilage of the upper eyelid, conjunctiva sclera. These elements are sometimes difficult to consider due to severe sclera hyperemia, but if 1-2 drops of 0.1% adrenaline solution are instilled into the conjunctival sac, hyperemia disappears and Chiari-Avtsyn spots can be detected in 90% of patients with typhus (Avtsyn’s adrenaline test )

An early sign is the enanthema, which is very characteristic and is important for early diagnosis. It was described by N. K. Rosenberg in 1920. On the mucous membrane of the soft palate and tongue, usually at its base, as well as on the front arches, you can notice small petechiae (up to 0.5 mm in diameter), their number is more often 5-6, and sometimes more. A careful examination of the Rosenberg enanthema can be detected in 90% of patients with typhus. It appears 1-2 days before the appearance of skin rashes. Like Chiari-Avtsyn spots, it persists until the 7th-9th day of illness. It should be noted that with the development of thrombohemorrhagic syndrome, similar rashes can appear in other infectious diseases.

With severe intoxication in patients with typhus, a peculiar coloration of the skin of the hands and feet can be observed, it is characterized by an orange tint, this is not yellowness of the skin, especially since there is no subictericity of sclera and mucous membranes (where, as you know, yellowness manifests itself earlier). Associate Professor of the Department of Infectious Diseases I.F. Filatov (1946) proved that this color is due to a violation of carotene metabolism (carotene xanthochromia).

The characteristic rash, which determined the name of the disease, appears more often on the 4th-6th day (most often it is noticed on the morning of the 5th day of illness), although the most typical period of occurrence is the 4th day. The appearance of a rash indicates the transition of the initial period of the disease to the high season. A characteristic feature of typhoid exanthema is its petechial roseole nature. It consists of roseola (small red spots with a diameter of 3-5 mm with blurry borders that do not rise above the skin level, roseola disappear with pressure on the skin or stretch it) and petechiae – small hemorrhages (diameter about 1 mm), they do not disappear when the skin is stretched . There are primary petechiae that appear on the background of previously unchanged skin, and secondary petechiae that are located on roseola (when the skin is stretched, the roseoleous component of exanthema disappears and only a point hemorrhage remains). The predominance of petechial elements and the appearance of secondary petechiae on most roseols indicates a severe course of the disease. Exanthema in typhus (unlike typhoid fever) is characterized by abundance, the first elements can be seen on the lateral surfaces of the trunk, upper half of the chest, then on the back, buttocks, less rash on the hips and even less on the legs. It is extremely rare for a rash to appear on the face, palms and soles. Roseola quickly and without a trace disappear from the 8th-9th day of illness, and at the site of the petechia (like any hemorrhage), a color change is noted, first they are bluish-violet, then yellowish-greenish, disappear more slowly (within 3-5 days). The course of the disease without a rash is rare (8-15%), usually in children.

Significant changes in the respiratory system in patients with typhus are usually not detected, there are no inflammatory changes in the upper respiratory tract (the redness of the pharyngeal mucosa is caused not by inflammation, but by injection of blood vessels). In some patients, increased breathing (due to excitation of the respiratory center) is noted. The appearance of pneumonia is a complication. Changes in the circulatory system are observed in most patients. This is manifested in tachycardia, a decrease in blood pressure, muffling of heart sounds, ECG changes, a picture of an infectious-toxic shock may develop. The defeat of the endothelium causes the development of thrombophlebitis, sometimes blood clots also form in the arteries, in the period of convalescence there is a threat of pulmonary embolism.

In almost all patients, an enlargement of the liver is detected quite early (from the 4th-6th day). An increase in the spleen is detected somewhat less frequently (in 50-60% of patients), but at an earlier time (from the 4th day) than in patients with typhoid fever. Changes in the central nervous system are characteristic manifestations of typhus, which has long been noticed by Russian doctors (“nervous mass horny”, in the terminology of Y. Govorov). From the first days of the disease, the appearance of a severe headache, a peculiar arousal of patients, which manifests itself in verbosity, insomnia, is irritated by light, sounds, touching the skin (hyperesthesia of the senses), there may be violent attacks, attempts to escape from the hospital, impaired consciousness, delirious condition, impaired consciousness, delirium, the development of infectious psychoses. In some patients, from the 7-8th day of the disease, meningeal symptoms appear. In the study of cerebrospinal fluid, there is a slight pleocytosis (not more than 100 leukocytes), a moderate increase in protein content. Damage to the nervous system is associated with the appearance of signs such as hypomimia or amimia, smoothness of nasolabial folds, deviation of the tongue, difficulty in protruding it, dysarthria, impaired swallowing, nystagmus. In severe forms of typhus, Govorov-Godelier symptom is detected. It was first described by Y. Govorov in 1812; Godelier described it later (1853). The symptom is that at the request to show the tongue, the patient sticks it out with difficulty, jerky movements and the tongue cannot stick out further than the teeth or lower lip. This symptom appears quite early – before the appearance of exanthema. Sometimes it is detected with a milder course of the disease. Some patients have a general tremor (trembling of the tongue, lips, fingers). At the height of the disease, pathological reflexes, signs of a violation of oral automatism (Marinescu-Radovici reflex, proboscis and distansorial reflexes) are detected.

The duration of the course of the disease (if antibiotics were not used) depended on the severity, with mild forms of typhus, typhoid fever lasted 7-10 days, recovery came quite quickly, and there were usually no complications. With moderate forms, the fever reached high numbers (up to 39-40 ° C) and lasted for 12-14 days, exanthema was characterized by the predominance of petechial elements. Complications may develop, but the disease, as a rule, ended in recovery. In severe and very severe cases of typhus, high fever was observed (up to 41-42 ° C), pronounced changes in the central nervous system, tachycardia (up to 140 beats / min and more), and a decrease in blood pressure to 70 mm Hg. Art. and below. The rash is hemorrhagic in nature, along with petechiae, larger hemorrhages and severe manifestations of thrombohemorrhagic syndrome (nosebleeds, etc.) may also appear. Erased forms of typhus were also observed, but they often remained unrecognized. The above symptoms are characteristic of classic typhus. When prescribing antibiotics, the disease stops within 1-2 bitches.

Complications. Rickettsia Provacheka parasitize in the vascular endothelium, in connection with this, various complications can occur – thrombophlebitis, endarteritis, pulmonary thromboembolism, cerebral hemorrhage, myocarditis. Predominant localization in the central nervous system leads to complications in the form of psychosis, polyradiculoneuritis. The addition of a secondary bacterial infection can lead to the addition of pneumonia, otitis media, mumps, glomerulonephritis, etc. With antibiotic therapy, when all manifestations of the disease pass very quickly, and even with mild forms of the disease, pulmonary thromboembolism is almost the only cause of death, as a rule, this has already happened in the recovery period, at normal body temperature, often the complication was provoked by the expansion of the motor activity of the convalescent.

Diagnosis of Epidemic Typhus

The diagnosis of sporadic cases in the initial period of the disease (before the appearance of a typical exanthema) is very difficult. Serological reactions also become positive only from the 4th to 7th day from the onset of the disease. During epidemic outbreaks, the diagnosis is facilitated by epidemiological data (information about the incidence, the presence of overstatement, contact with patients with typhus, etc.). With the appearance of exanthema (i.e., from the 4th to 6th day of illness), a clinical diagnosis is already possible. The timing and nature of the rash, facial flushing, Rosenberg enanthema, Chiari-Avtsyn spots, changes in the nervous system – all this makes it possible to differentiate primarily from typhoid fever (gradual onset, inhibition of patients, changes in the digestive system, later onset of exanthema in the form of a roseolo-papular monomorphic rash, lack of petechiae, etc.). It is necessary to differentiate from other infectious diseases that occur with exanthema, in particular, with other rickettsioses (endemic typhus, tick-borne rickettsiosis of North Asia, etc.). Some differential diagnostic value has a blood picture. In typhoid fever, moderate neutrophilic leukocytosis with a stab shift, eosinopenia and lymphopenia, and a moderate increase in ESR are characteristic.

Various serological reactions are used to confirm the diagnosis. The Weil-Felix reaction — the agglutination reaction with the OXig protea — retained some significance, especially when the antibody titer increased during the course of the disease. More often they use CSC with a rickettsial antigen (prepared from Provacheka rickettsia), the diagnostic titer is considered to be 1: 160 and higher, as well as an increase in the antibody titer. Other serological reactions are also used (the reaction of microagglutination, hemagglutination, etc.). In the memorandum of the WHO meeting on rickettsiosis (1993), an indirect immunofluorescence reaction was recommended as the recommended diagnostic procedure. In the acute phase of the disease (and the convalescence period), antibodies are associated with IgM, which is used to distinguish from antibodies as a result of a previous illness. Antibodies begin to be detected in blood serum from the 4th to 7th day from the onset of the disease, the maximum titer is reached after 4-6 weeks from the onset of the disease, then the titers slowly decrease. After suffering from typhus, Rickettsia Provachek for many years remain in the body of the convalescence, this leads to a long-term preservation of antibodies (they are also associated with IgG for many years, albeit in low titers). Recently, for diagnostic purposes, trial therapy with tetracycline group antibiotics has been used. If during the administration of tetracycline (in usual therapeutic doses) after 24-48 hours normalization of body temperature does not occur, then this allows to exclude typhus (if fever is not associated with any complication).

Treatment for Epidemic Typhus

The main etiotropic drug is currently the tetracycline group antibiotics, and with intolerance, chloramphenicol (chloramphenicol) is also effective. More often, tetracycline is prescribed orally at 20-30 mg / kg or for adults 0.3-0.4 g 4 times a day. The course of treatment lasts 4-5 days. Less commonly prescribed chloramphenicol 0.5-0.75 g 4 times a day for 4-5 days. In severe forms, the first 1-2 days, you can prescribe chloramphenicol sodium succinate intravenously or intramuscularly, 0.5-1 g 2-3 times a day, after normalization of body temperature, they switch to oral administration of the drug. If, against the background of antibiotic therapy, a complication due to the layering of a secondary bacterial infection (for example, pneumonia) joins, then, taking into account the etiology of the complication, an appropriate chemotherapy is additionally prescribed.

Etiotropic antibiotic therapy has a very quick effect and therefore many methods of pathogenetic therapy (vaccine therapy developed by Professor P. A. Alisov, long-term oxygen therapy, justified by V. M. Leonov, etc.) currently have only historical significance. Of pathogenetic drugs, it is mandatory to prescribe a sufficient dose of vitamins, especially ascorbic acid and P-vitamin preparations, which have a vasoconstrictive effect. To prevent thromboembolic complications, especially in risk groups (these primarily include the elderly), the appointment of anticoagulants is necessary. Their appointment is necessary to prevent the development of thrombohemorrhagic syndrome. The most effective drug for this purpose is heparin, which should be prescribed immediately after the diagnosis of typhus and the continuation of its intake for 3-5 days.

Heparin (Irrelevant), synonyms: Heparin sodim, Heparin BC, Heparoid. Available in the form of a solution in bottles of 25,000 units (5 ml). It should be borne in mind that tetracyclines to some extent weaken the effect of heparin. Enter intravenously in the first 2 days at 40,000-50,000 units / day. It is better to administer the drug drip with glucose solution or divide the dose into 6 equal parts. From the 3rd day, the dose is reduced to 20,000-30,000 units / day. If embolism has already arisen, the daily dose on the first day can be increased to 80,000-100,000 units. The drug is administered under the control of the blood coagulation system.

Forecast. Before the introduction of antibiotics into practice, the prognosis was serious, many patients were dying. Currently, in the treatment of patients with tetracyclines (or chloramphenicol), the prognosis is favorable even in severe cases of the disease. Lethal outcomes were observed very rarely (less than 1%), and after the introduction of anticoagulants into practice, fatal outcomes were not observed.

Prevention of Epidemic Typhus

For the prevention of typhus, typhoid fever, early diagnosis, isolation and hospitalization of patients with typhus are of great importance, careful sanitization of patients in the hospital’s emergency room and disinsection of the patient’s clothes are necessary. For specific prophylaxis, a formalin-inactivated vaccine containing killed Provacheka rickettsia was used. Vaccines were used during the increased incidence and were effective. Currently, with the presence of active insecticides, effective methods of etiotropic therapy and low morbidity, the value of typhoid vaccination has significantly decreased.