ROCKY MOUNTAIN SPOTTED FEVER

Rocky Mountain spotted fever belongs to the large group of spotted fevers -tick and mite-borne zoonotic infections.

Historic reference

Rocky Mountain spotted fever (RMSF) was first described in Idaho in the late nineteenth century. Ricketts established the infectious nature of the illness and demonstrated the role of the tick as the vector in western Montana in 1906.

Etiology

The etiologic agent, Rickettsia rickettsii, belongs to the spotted fever group of rickettsia, which are genetically related but differ from one another in their surface antigenic proteins.

Spotted fever group rickettsial are obligate intracellular bacteria that reside in the cytosol and less often in the nucleus of their host cells. The rickettsiae are small, the cell wall has the ultrastructural appearance of a gram-negative bacterium and contains lipopolysaccharide.

Among the protein antigens of Rickettsia rickettsii, two surface proteins contain heat labile epitopes that seem critical to immunity. Some epitopes of these proteins are species specific, and others are spared among the members of the group.

' The lipopolysaccharide of spotted fever group rickettsiae contains highly immunogenic antigens that are strongly cross-reactive among all members of the group.

Epidemiology

The usual method of transmission in nature is through the bite of the tick. The tick is both the vector and the main reservoir. Dermaceptor variables, the American dog tick, is the prevalent vector in the eastern United States; D. andersoni, the Rocky Mountain wood tick in the western States; Rhipicephalus sanguineous - in Mexico.

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Rickettsia rickettsii is transmitted trans-stadially and transovarially in ticks, thus maintaining the agent in nature. Of three tick stages, larva, nymph, and adult, only the adult Dermaceptor ticks feed on humans.

The tick transmits the disease to humans during feeding. The bite is painless and frequently unnoticed. After the attached tick has fed for 6-Þ hours,rickettsia are released from the salivary glands. An even longer period may be required for reactivation of rickettsial virulence in unfed ticks. Human may also be infected by exposure to infective tick hemolymph during the remove of tick from humans or domestic animals, especially when the tick is crushed between the fingers. Most cases of Rocky Mountain spotted fever are diagnosed during late spring and summer.

Pathogenesis

Rickettsiae introduced into the skin apparently spread via lymphatic and small blood vessels to the systemic and pulmonary circulation where they attach to and enter their target cells, the vascular endothelium, to establish numerous disseminated foci of infection. After entry by induced phagocytosis, the rickettsiae escape from the phagosome into the cytoplasm and less frequently the nucleus. Rickettsiae proliferate intracellular by binary fission and are released than the infected cells via long thin cell projections. The presence of large quantities of rickettsiae in damaged cells supports the concept of direct cell injury. The major pathophysiologic effect of endothelial cell injury is increased vascular permeability, which in turn results in edema, hypovolemia, hypotension and hypoalbuminemia. High quantities of rickettsiae infecting the pulmonary microcirculation increase the vascular permeability and cause noncardiogenic pulmonary edema.

Anatomic pathology

Vascular injury and the subsequent host mononuclear leukocytic response correspond to the distribution of rickettsiae and include interstitial pneumonia, interstitial myocarditis, perivascular glial nodules of the central nervous system, and similar vascular lesions in the rash, gastrointestinal tract, pancreas, liver, skeletal muscles, and kidneys. Severe vascular injury may lead to hemorrhage.

Clinical manifestations

The incubation period ranges from 2 to 14 days, with a medium of 7 days. Rocky Mountain spotted fever is one of the most serious rickettsioses. There is no primary affect. The disease usually begins with fever, myalgia, and headache. Gastrointestinal involvement with nausea, vomiting, abdominal pain, diarrhea, and abdominal tenderness occurs in substantial portions of patients and may suggest gastroenteritis or an acute surgical abdomen.

The rash, the major diagnostic sign, appears in a small fraction of patients on the first day of the disease, usually appearing 3-5 days after the onset of fever. The rash typically begins around the wrists and ankles but may start on the trunk or be diffuse at the onset. Skin necrosis or gangrene develops in 4 %

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of cases as a result of rickettsial damage to the microcirculation. Gangrene involves the digits or limbs and occasionally requires amputation.

Headache is usually quite severe. Focal neurologic deficits, transient deafness, meningismus, and photophobia may suggest meningitis or meningoencephalitis.

Renal failure is an important problem in severe Rocky Mountain spotted fever. Prerenal azotemia related to hypovolemia responds to intravenous hydration; however, acute tubular necrosis may require hemodialysis. Pulmonary involvement is suggested by cough and radiological changes including alveolar infiltrates, interstitial pneumonia and pleural effusion. The liver and spleen are increased. The changes of the central nervous system are typically: the severe diffuse headache, sleeplessness, exiting, delirium and hallucinations, paralysis, decreasing of the hearing and vision, psychical changes, neurosis. This changes may be maintained for a long time (till month and more), but than they disappear without consequences. The duration of the acute period of the disease is 2-3 weeks. The recovery comes slowly, sometime during some months.

There are ambulatory, aborted, typical and malignant (fulminate) forms of the disease. The fulminate form is characterized by severe toxicosis and lethal result during 3-4 days. This form of Rocky Mountain spotted fever was described in the literature as Brazilian typhus fever.

Complications

At present time the complications are observed rarely. It may be hemorrhages, phlebitis, neuritis, myocarditis.

Diagnosis

Serology, the usual method for confirmation of the diagnosis, is retrospective, serum antibodies becoming detectable during convalescence. Four methods for the detection of antibodies to specific rickettsial antigens are indirect hemagglutination, indirect immunofluorescence, latex agglutination and complement fixation. The biological methods may be used (the infection by blood of the patient of guinea-pigs and following detachment of the agent).

Differential diagnosis

The differential diagnosis at the first consultation includes typhoid fever, measles, rubella, respiratory tract infection, gastroenteritis, acute surgical abdomen, viral meningoencephalitis, meningococcemia, leptospirosis, thrombotic thrombocytopenic purpura, infectious mononucleosis and other rickettsial diseases.

Treatment

The methods of the treatment are similar to epidemic typhus fever. Since the introduction of chloramphenicol and the tetracycline, including doxycycline, the lethality of the disease decreased dramatically to 3-7 %.

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Prophylaxis

There are two ways of the prophylaxis: the struggle with ticks and vaccination of persons in the endemic areas (formalized Cox vaccine).

SCRUB TYPHUS (TSUTSUGAMUSHI FEVER)

Scrub typhus is an acute, febrile illness of humans that is caused by Rickettsia tsutsugamushi (R. orientalis), it is transmitted to human by the bite of larval -stage thrombiculid mites.

Historic reference

At the first the disease was described in Japan in 1810 year by Huchimoto which called this disease "tick's disease". Scrub fever occurs over a wide area of Earsten Asia, and the Western Pacific region, from Korea to Australia, and from Japan to India (the areas of the mountains) and Pakistan.

Etiology

Rickettsia orientalis is an obligate intracellular bacterium that grows free in the cytoplasm of infected cells, that has no vacuolar membrane. The organism can best be seen in tissue by using the Giemsa stain. It is rather unusual among rickettsiae because of its large number of serotypes.

Epidemiology

Scrub typhus is a zoonotic infection. The principal reservoir of the infection is thrombiculid mites. The supplementary reservoir is rodents. In endemic areas the infection of the man is happened in the places with scrubs and forests, where the trombiculid mites live. The larval chigger the agent of the disease with blood and transmittes it transovarially to the new generations of the chiggers. So, only the new generation of the chiggers may transfer the agent to the human and animals next year. The disease is registered frequently in July-August.

Pathogenesis

The links of the pathogenesis may be represented in the next form:

1. Inculcation of Rickettsiae into human organism (after the site of the trombiculid mite). In the laboratory conditions it may be penetration of the agent through the mucous membranes of the eyes and by the aerogenic way.

2. Parasitation of the Rickettsiae at the endothelial cells of the vessels with forming of the first affect regional lymphadenopathy.

3. Penetration of the Rickettsiae into the circulative system, development at the endothelial cells of the vessels and forming of the granulomas.

4. Rickettsiaemia with forming of the generalized polyadenitis.

5. Intoxication.

6. Diffusive entering of the agent into parenchimatous organs and tissues.

1.

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7. The development of the inflammatory changes in .the mucous cavities (pericardial, pleuritic, abdominal) and appearance of the exudation.

8. Development of the reactive allergic reactions.

9. Immunological reactions.

Anatomic pathology

The morbid anatomy of scrub typhus have a large similarity with the morbid anatomy of endemic typhus. The primary affect and regional lymphadenopathy are typical.

Clinical manifestation

The period of the incubation is from 5 to 21 day (often 7-11 day). The onset is usually sudden and is characterized by fever, severe headache, and myalgia. There is usually tender lymphoadenopathy in the region of the bite wound or eschar. Temperature usually rises quickly in the first several days of disease to 40-40.5 °Ñ. Early in the course of illness, the pulse is relatively slow. Other symptoms at this time may include ocular pain, conjunctival injection, nonproductive cough, and apathy. After about 5 days of illness, rash occurs on the body and spreads to the extremities; it begins as a macular rash and may become papular. It is sometimes evanescent. At this time, there is generalized lymphoadenopathy and splenomegaly.

In untreated patients, fever subsides after an illness of about 2 weeks. Specific antirickettsial therapy shortens the illness considerably and reduces mortality to essentially nil. Mortality rates have ranged in untreated patients.

Complications

In a small proportion of patients, tremors, delirium, nervousness, slurred speech, deafness, or nuchal rigidity may develop in the second week of illness. Cerebrospinal fluid from such patients is either normal.

Diagnosis

The methods of the laboratory diagnostic are serological. Because of the susceptibility of white mice to R. orientalis, intraperitoneal injection of patient's blood can be used diagnostically.

Differential diagnosis

The differential diagnosis includes typhoid fever, brucellosis, leptospirosis, infectious mononucleosis and flavivirus infection such as dengue fever.

Treatment

Tetracycline or chloramphenicol are both effective in treating scrub typhus; fever dissipates in less than 24 hours in most patients.

Evidence is accumulating that shows single - dose doxycycline therapy to be effective in treating scrub typhus and in preventing relapse (200 mg orally weekly).

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Prophylaxis

Individuals who travel to endemic areas should wear protective clothes and use insect repellants to avoid chigger bites.

An effective vaccine for humans has not been developed.

Q - FEVER

Q-fever is zoonotic infection. It occurs worldwide. Q-fever has acute, subacute and chronic course. It is characterized by polymorphic clinical manifestations.

Historic reference

Derrick, a medical officer of health in Australia in 1935 investigated a febrile illness that affected 20 of 800 employs of Brisbane meat works. He coined the term "Q (or query) fever". Burnet and Freeman showed that the organism isolated from the blood and urine of these patients was a rickettsia. At about the same time Davis and Cox isolated a microorganism from ticks {Dermaceptor andersoni). Later Dyer showed that R. burnetii (Burnet and Freeman's organism) was the same as R. diaporica (Cox's organism) - it is now known as Coxiella burneti. Q-fever has been reported from at least 51 countries on five continents.

Etiology

Coxiella burneti, the etiologic agent of Q fever, is a highly pleomorphic coccobacillus with a gram-negative cell wall. Large and small cell variants exist, and spore stage has been described. Coxiella burneti has ability passing through bacterial filters. They may transform into L-forms by action of antibiotics. Coxiella burneti is steady in the external environment. They don't perish in pasteurization of the milk. They perish only in boiling during 10 minutes. Coxiella burneti may preserve in the dry cultures and secretions during some years.

Epidemiology

The principal reservoir of the agent is the wild animals and domestic animal (92 species), the wild and domestic birds (72 species), ticks (73 species). In animals the agent detaches into external environment with fecal matter. The infection happens by the aerosol rate or in eating of the corpses of the animals. The agricultural animals have the principal epidemiological meaning (cows,sheep, horses, pigs, camels and other). The infection of the human happens by the aerosol rate, alimentary, contactive or transitive rate.

The most common animals reservoirs for this zoonosis are cattle, sheep and goats. These domestic ungulates, when infected, shed the agent in urine, feces, milk and especially in birth products. The placenta of infected sheep contains up to 109 organisms per gram of tissue. Coxiella burneti has also been isolated from human milk, and human placentas.

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Pathogenesis

There are the next links of the pathogenesis:

1. Inoculation of the agent into the organism through the damaged mucous membranes and skin.

2. Lymphagenic spreading of the agent into the circulative system.

3. Primary rickettsiaemia.

4. Dissemination of the rickettsia into the parenchimatous organs of the reticuloendothelial system.

5. Reproduction and development of the rickettsiae in the histiocytes and macrophages.

6. Secondary rickettsiaemia and toxinemia with dissemination in new focuses of reticuloendothelial system.

7. Development of the allergic manifestations.

8. Formation of the immunity and convalescence.

Anatomic pathology

Q-fever is of high quality reticuloendotheliosis without development of panvasculitis. It's anatomic pathology is similar with others rickettsioses. The typical "doughnut granulomas" is seen on liver biopsy. This is a granulomas with a dense fibrin ring surrounded by a central lipid vacuole. C. burnetii has been isolated from the liver of patients with Q-fever hepatitis, but the organism has not been visualized within the hepatic parenchyma.

Clinical manifestation

An incubation period is from 2 till 30 days (in aberage - 20 days). The disease begins acuity. The severe headache, weakness, fever, chills, fatigue, myalgia are observed in the patients. The clinical manifestations are polymorphs. The prolongation of the fever is different ( from 2 till 2-4 weeks). It may be recurrences of the fever through 4-8 days of the normal temperature. It may be the rash on the 6-8 days of the disease without clear localization (rose-spot, papular, petechial).

There are several clinical syndromes as a result of C. burnetii infection:

1. A self-limited febrile illness (2-14 days).

2. Pneumonia.

3. Endocarditis.

4. Hepatitis.

5. Osteomyelitis.

6. Q-fever in the immunocompromised host.

7. Q-fever in infancy.

8. Neurologic manifestation - encephalitis, aseptic meningitis, toxic confusional states, dementia, extrapyramidal disease, manic psychosis.

Self-limited febrile illness - this is probably the most common form of Q-fever. In many areas 11-12 % of individuals have antibodies to C. burnetii -most do not recall pneumonia or other severe illness. It is likely that the age at

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which infection occurs and the dose of the agent determine whether or not Q-fever is a mild self-limited febrile illness. There is also a suggestion that some infections may be totally asymptomatic.

Pneumonia. There are three presentations of this form of Q-fever: atypical pneumonia, rapidly progressive pneumonia, and pneumonia as an incidental finding in a patient with a febrile illness.

Endocarditis - is the prime manifestation of "chronic" Q-fever. Q fever endocarditis is rare in children. The manifestations are the same as those in adults.

Hepatitis. There are three kinds of Q-fever hepatitis:

1. An infectious hepatitis-like picture.

2. As an incidental finding in a patient with acute Q-fever pneumonia.

3. Fever of unknown origin with characteristic granulomas on liver biopsy. Neurologic manifestations, vertebral osteomyelitis and infection in the

immunocompromised host are uncommon manifestations of Q-fever.

In the peripheral blood the leucopenia,lymphocytosis,monocytosis occur,an

accelerated ESR.

Complications

The complications includes hemorrhages, phlebitis, neuritis, myocarditis, vertebral osteomyelitis, bone marrow necrosis, hemolytic anemia.

Diagnosis

In diagnostics the serological methods may be used (reaction of agglutination and compliment fixation) and also the skin-allergic test with allergen (antigen from the killed Coxiella burneti). The materials for recovering of the agent are blood, urine, cerebrospinal fluid, mammary milk, sputum. In diagnostics of Q-fever the biological test may be used on guinea-pigs and white mice.

Differential diagnosis

Differential diagnosis of Q-fever is performed with grippe,epidemic typhus, typhoid fever and paratyphoid, brucellosis, ornithosis, acute pneumonia, sepsis.

Treatment

The most effective etiotropic remedy is antibiotics of the group of tetracycline. Tetracycline is prescribed on 2 gm a day till 7-10 day of the normal temperature. The prescription anti-inflammatory and antihistamine remedies is indicated in connection with allergic reorganization of the organism, especially in prolonged and chronic forms of the disease with serious duration.

Prophylaxis

Prophylaxis includes complex veterinary, antiepidemiological and sanitary-hygienic measures. The. specific prophylaxis is carried out using killed or living vaccine. In Q-fever endemic areas persons, working with animals, must be vaccinated.

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Control questions:

1. Classification of rickettsioses.

2. Etiology, epidemiology and incidence of epidemic typhus fever.

3. Main clinical symptoms and signs of epidemic typhus fever.

4. Pathogenesis and morbid anatomy of epidemic typhus fever.

5. Clinical manifestations of disease.

6. The variants of the course of the disease.

7. Complications of epidemic typhus fever infection.

8. Laboratory diagnosis of epidemic typhus fever.

9. Treatment of epidemic typhus fever.

10. Etiology and epidemiology of Brill-Zinsser disease and other rickettsioses.

11. Main clinical symptoms and signs of Brill-Zinsser disease and other rickettsioses.

12. Clinical manifestations of Brill-Zinsser diseases.

13. Laboratory diagnosis of Brill-Zinsser disease and other rickettsioses.

14. Treatment of rickettsioses.

15. Preventive measures against rickettsioses.

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Date: 2014-12-21; view: 1243