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Typhus fever

• Typhus refers to a group of zoonotic diseases caused by bacteria that are spread to humans by fleas, lice, and chiggers.
• Typhus fevers include scrub typhus, murine typhus, and epidemic typhus.
• The most common symptoms are fever, headaches, and sometimes rash.

Historical perspective

• In 1083, Typhus was first identified as a disease in Spain.
• In 1489, during the Spanish siege of Moorish Granada, the first reliable description of the disease was made.
• In 1546, Fracastoro extensively described the disease and distinguished it from plague in his book Contagione.
• In 1676, Von Zavorziz wrote a book on typhus called The Infection of Military Camps.
• In 1739, Huxham stated typhus and typhoid as two different entities, later in the same year Boissier de Sauvages confirmed this and called it exanthematic typhus.
• In 1829, Louis, French clinician clearly differentiated Typhus Fever from Typhoid Fever.
• In 1836, Gerhard(United States) clearly distinguished the two diseases from each other based on pathologic findings.
• In 1909, Charles Nicolle for the first time described the role of lice bite in transmission of typhus. In 1928, he was awarded the Nobel Prize for his discovery.
• In 1916, Weil and Felix reported the isolation of a Proteus that was agglutinated by the sera of patients with typhus, which was the basis for the first serological test for the disease.
• In 1916, DaRocha-Lima isolated and identified Rickettsia prowazeki.
• In 1926, Maxcy described the various forms of typhus.
• In 1938, Starzyk demonstrated that patients are infected by the feces and not the bite of the louse.
• In 1922, Wolbach described the human histopathology of R prowazekii infection.
• In 1938, Cox was successful in growing cell cultures of R prowazekii in embryonated eggs.
• In 1940, Cox and Bell prepared an Epidemic Typhus vaccine based upon the use of tissue culture.
• In 1943–1944, during World war II DDT (a pesticide) was employed to control lice and typhus.
• In 1998, Andersson et al, sequenced the entire genome after much study of the fundamental mechanisms of R prowazekii's intracellular life and its effects on host cells.

Pathophysiology

Typhus fever is a zoonotic disease, Humans could be infected by bites from ticks, lice, inhalation of the bacteria, and direct contact of bacteria with skin wounds or mucous membranes. Following transmission, white blood cells phagocyte the pathogen and transports it via hematologic or lymphatic route to different organs, specially to those of the reticuloendothelial system. The pathophysiology of typhus fever can be described in the following steps.

Transmission

• Rickettsial pathogens are harboured by parasites such as fleas, lice, mites, and ticks.
• Organisms are transmitted by the bites from these parasites or by the inoculation of infectious fluids or feces from the parasites into the skin.

class="wikitable"

Disease	Etiological agent	Vector
Epidemic typhus	Rickettsia prowazekii	Human body louse
Murine typhus	Rickettsia typhi	Infected fleas
Scrub typhus	Orientia tsutsugamushi	Larval mites

Dissemination

• Scratching a louse-bite site allows the rickettsia-laden excrement to be inoculated into the bite wound.
• Following transmission, rickettsia are ingested by macrophages and polymorphonuclear cells. On ingestion, they replicate intracellularly inside the lysed cells and disseminate systemically.

Incubation

Incubation period of Typhus fever varies from one to two weeks.

Pathogensis

• On transmission, Rickettsia is actively phagocytosed by the endothelial cells of the small venous, arterial, and capillary vessels.
• It is followed by systemic hematogenous spread resulting in multiple localizing vasculitis. The major pathology is caused by vasculitis and its complications.
• This process of inflammatory response (aggregation of leukocytes, macrophages, and platelets) along with occlusion of small blood vessels results in formation of nodules.
• Occlusion of supplying blood vessels also causes gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia.
• This vasculitic process also results destruction of the endothelial cells and leakage of the blood leading to volume depletion and subsequent decreased tissue perfusion and, possibly, organ failure.
• Endotheleal damage lead to activation of clotting system

Natural history

fatal in 20%–60% of untreated cases

History

• History of travel to endemic areas
• History of tick bite

Symptoms

Most common symptoms

• Fever
• Headache
• Malaise
• Maculopapular, vesicular, or petechial rash
• Eschar
• Nausea and vomiting.

Less common symptoms

• Abdominal pain
• Cough
• Prostration
• Confusion
• Photophobia
• Diarrhea

Lab diagnosis

• Laboratory studies are not particularly helpful in confirming a diagnosis of typhus.
• They assess the degree of severity of the illness and in help in excluding other diseases.
• The diagnosis of typhus is clinically suggested when the appropriate historical elements are elicited from a patient who presents with the characteristic symptoms and signs.
• Antibiotic therapy should begin promptly when the diagnosis is suspected; thereafter, appropriate laboratory studies can be serially performed as needed.
• Diagnosis may be confirmed using laboratory tests; however, more than one week may pass before patients mount a demonstrable immune response that can be measured serologically.
• Typhus is a vasculitic process, any organ may be affected, and multiorgan system dysfunction or failure may occur if the illness is not diagnosed and treated in the early stages.
• Renal - Azotemia/proteinuria
• Hematologic
• Leukopenia (common in the early stages of disease)
• WBC count normal/mildly elevated later
• Thrombocytopenia
• Hepatic - Mild transaminase elevations
• Metabolic - Hypoalbuminemia/electrolyte abnormalities (particularly hyponatremia)
• Indirect immunofluorescence assay (IFA) or enzyme immunoassay (EIA) testing can be used to evaluate for a rise in the immunoglobulin M (IgM) antibody titer, which indicates an acute primary disease.
• Brill-Zinsser disease can be confirmed in a patient with a history of primary epidemic typhus who has recurrent symptoms and signs of typhus and a rise in the immunoglobulin G (IgG) antibody titer, which indicates a secondary immune response.
• IFA and EIA tests can be used to confirm a diagnosis of typhus, but they do not identify the various rickettsial species.
• Polymerase chain reaction (PCR) amplification of rickettsial DNA of serum or skin biopsy specimens can be used for diagnosing typhus. [9]
• The complement fixation (CF) test is a serological test that can be used to demonstrate which specific rickettsial organism is causing disease by detection of specific antibodies.

Histologic Findings

• Rickettsia may be observed in tissue sections using Giemsa or Gimenez staining techniques.

Xray chest

• No imaging studies are specifically indicated to aid in diagnosing typhus.
• Imaging studies are indicated only on a case-by-case basis to evaluate potential complications or as needed.
• Chest radiography may be a complementary tool to evaluate the clinical course of scrub typhus.
• Chest radiographic examinations should be obtained during the first week after the onset of illness.

Colonic abscess

A colonic abscess develops as a complication of diverticulitis. A colonic abscess is a localized collection of pus within the wall of the colon that may cause swelling and destroy tissue. If the abscess is small and remains within the wall of the colon, it may clear up with antibiotics alone. If the abscess is large > 5cms, or unresponsive to medical treatment, it must be drained using a catheter facilitated by sonography or x-ray.

Causes

Arises as a complication of diverticulosis or diverticulitis.

Pathophysiology

• The primary process is thought to be an erosion of the diverticular wall by increased intraluminal pressure or inspissated food particles.
• Inflammation and focal necrosis ensue, resulting in the abscess formation.

Risk factors

Risk factors in the development of colonic abscess include same as that of diverticular diseases of the colon, such as advanced age, chronic constipation, connective tissue diseases (such as Marfan syndrome or Ehlers-Danlos syndrome), low dietary fiber intake, high intake of fat and red meat, and obesity.