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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

Colon abscess is a rare entity and arises as a compliecation of diseases such as IBD, colorectal cancer, diverticulosis or diverticulitis. Natural gut flora which includes gram negative and anaerobic bacteria play a major role in the development of colonic abscess.

Most common causes

• Enterococcus
• Escherichia coli
• Staphylococcus aureus
• Bacteroides fragilis
• Clostridium perfringens

Less common causes

• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Proteus

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.

Gross Pathology

• The serosal surface of the colon looks pale with rough edges and yellowish exudate along with hyperemia

Microscopic findings

• A focally necrotic debris is seen in the mucosal wall.
• Intravascular fibrin is seen in medium-sized blood vessels.
• Clusters of neutrophils are seen on the serosal aspect.

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.

Screening

Screening for colonic abscess is not recommended in the general population.

Epidemiology and Demographics

Prevalance

• The prevalence of diverticulosis is age-dependent.
• The prevalence increases from fewer than 20% at age 40 to approximately 60% by age 60.

Incidence

• Incidence rates among age groups 18 to 44 is 0.151 to 0.251 per 1000 population.
• Incidence rates among age groups 45 to 64 years of age is 0.659 to 0.777 per 1000 population.

Gender

• At young age (<50 years), males are more commonly affected with diverticulosis than females.
• At older age, women are more frequently affected with diverticulosis than males.

Race

• There is a slight racial predilection to the development of diverticulosis.
• Caucasian individuals are at higher risk of developing diverticulosis compared with Asian and non-African Black individuals.

Natural history

If left untreated colonic abscess will rupture through the wall, and this may eventually lead to death if peritonitis develops.

Complications

• Peritonitis
• Septicemia
• Hemorrhage
• Death

Prognosis

• Majority of the patients with colonic abscess recover quickly with drain and IV antibiotics, but complications can occur if treatment is delayed or if peritonitis occurs.[3][4]
• It usually takes between 10 and 28 days to recover completely.
• Typical abscess responds quickly to antibiotics and percutaneous drain and resolves spontaneously.

History and symptoms

The most common symptom of colonic abscess is left lower quadrant abdominal pain along with fever and chills. The most common sign is tenderness around the left side of the lower abdomen. Nausea, vomiting, chills, cramping, diarrhea and constipation may occur as well. The severity of symptoms depends on the extent of the infection.

Differentiating Colonic abscess from other diseases

Diseases	Clinical features					Diagnosis		Associated findings
	Symptoms				Signs	Laboratory fingdings	Radiological findings
	Fever	Abdominal pain	Nausea vomiting	Diarrhea
Crohn's disease	+	LLQ continuous localized pain	+	Bloody	Fullness or a discrete mass in the LLQ of the abdomen	[ASCA]) are found in Crohn disease	Transmural ulcerations are seen on colonoscopy	H/O weight loss, Extra intestinal manifestaions Endoscopic biopsy for diagnosis
Gastroenteritis (Bacterial and viral)	+	Diffuse crampy intermittent abdominal pain	+	Bloody or watery	Rebound tenderness, rash	Fecal leukocytes Stool culture Stool toxin assay	No specific findings	H/O food poisoning, travel
Primary peritonitis	+	Abrupt diffuse abdominal pain	+	Bloody/watery	Abdominal distension, rebound tenderness	Peritoneal fluid shows >500/microliter count and >25% polymorphonuclear leukocytosis.	X-ray abdomen identifies free air under the diaphragm CT demonstrates abscess or fluid in abdomen	History of advanced cirrhosis or nephrosis Peritoneal fluid analysis confirms the diagnosis
Pelvic inflammatory disease	+	Bilateral lower quadrant pain	+	-	Purulent discharge from cervical os. Cervical motion tenderness	Abundant white blood cells (WBCs) on saline microscopy of vaginal secretions Laboratory evidence of cervical infection with N gonorrhoeae or C trachomatis(via culture or DNA probe)	Transvaginal ultrasonographic scanning or magnetic resonance imaging (MRI) shows thickened fluid-filled tubes with or without free pelvic fluid or tubo-ovarian abscess (TOA).	Laparoscopy helps in confirmation of the diagnosis
Ruptured ectopic pregnancy	+	Diffuse abdominal pain	+	-	Unilateral or bilateral abdominal tenderness Abdominal rigidity, guarding On pelvic examination, the uterus may be slightly enlarged and soft, and cervical motion tenderness	BHCG hormone level is high in serum and in urine	Ultrasound reveals presence of mass in fallopian tubes.	Triad of amenorrhea, abdominal pain and vaginal bleeding SIgns of hypotension Transvaginal ultrasound with BHCG levels are the gold standard for diagnosis

Laboratory findings

Hematologic parameters suggestive of infection like, leukocytosis, anemia, abnormal platelet counts, and abnormal liver function frequently are present in patients with colonic abscess, although patients who are debilitated or elderly often fail to mount reactive leukocytosis or fever. Blood cultures indicating persistent polymicrobial bacteremia strongly implicate the presence of an abscess.

CT Abdomen

• Colonic and paracolic inflammation in the presence of underlying diverticula (diverticula are identified on CT scans as outpouchings of the colonic wall).
• Symmetric thickening of the colonic of approximately 4-5 mm is common.
• Enhancement of the colonic wall is commonly noted. This usually has inner and outer high-attenuation layers, with a thick middle layer of low attenuation.
• Free diverticular perforation results in the extravasation of air and fluid into the pelvis and peritoneal cavity.
• Air in the bladder in the presence of a nearby segment of diverticulitis is suggestive of a colovesical fistula.

Medical therapy

Antibiotics should be started immediately once the diagnosis of abscess is made. Preoperative antibiotics have been associated with lower rates of wound and intra-abdominal infections.

• 1 Emperic therapy:

• 1.1 Single agent:

• Preferred regimen (1): Imipenem-Cilastatin 500 mg IV q6h OR 1 g q8h
• Preferred regimen (2): Meropenem 1 g IV q8h
• Preferred regimen (3): Doripenem 500 mg IV q8h
• Preferred regimen (4): Piperacillin-tazobactam 3.375 g IV q6h

• 1.2 Combination:

• Preferred regimen (1): Cefepime 2 g q8–12 h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (2): Ceftazidime 2 g q8h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (3): Ciprofloxacin 400 mg q12h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (4): Levofloxacin 750 mg q24h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Note: Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome.

Surgery

Percutaneous drainage can be performed under ultrasound or CT guidance, using either the Seldinger or trocar technique. Ultrasound is limited if the abscess is small, obscured by other structures, or if precise placement is required because of nearby vessels or organs. In these cases, CT is the optimal imaging modality. When an abscess is deep in the pelvis, depending on the specific location of the fluid collection, access may be obtained via transgluteal, transvaginal, or transrectal approaches. If the fluid collection is sterile, a transgluteal approach is preferred because it allows for sterile technique. Depending on the location of abscess, patient is placed in prone or supine position on the CT table. Localization scan using CT allows in selecting a safe window of access into the collection. A coaxial micropuncture introducer set is advanced into the abscess under CT guidance. An Amplatz guidewire is advanced through the sheath and coiled within the abscess. After serial dilatation of the tract with a dilator, an pigtail drain is advanced over the guidewire and deployed. {{#ev:youtube|f5KvsjHaOnI}}

Prevention

Dietary fiber and a vegetarian diet may reduce the incidence of symptomatic diverticular disease by decreasing intestinal inflammation and altering the intestinal microbiota.. Vigorous physical activity appears to reduce the risk of diverticulitis and diverticular bleeding..