Sandbox:Aditya

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.

Pathogenesis

• 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 subsequently leading to decreased tissue perfusion and, possibly, organ failure.
• Endothelial damage lead to activation of clotting system

Natural history

Without treatment, fever may last 2 weeks, followed by a prolonged recovery time and a significantly greater chance of developing complications. Delay in treatment may result in advanced disease, including neurologic manifestations such as confusion, seizures, or coma, and widespread vasculitis (damage to the endothelial cells that line blood vessels).

Complications

• Hearing loss
• Myocarditis
• Vasculitis
• Aseptic meningitis

Prognosis

Prognosis depends on age and immunization status of the individual. With prompt, appropriate treatment, most individuals recover completely.The fatality rate for epidemic typhus varies from 1% to 20%.

History

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

Symptoms

Typhus fever	Rash
Scrub typhus	About 25–50% of scrub typhus patients develop a rash. The rash is usually macular or maculopapular. Typically, it will begin on the abdomen of an infected individual and then spread to the extremities. Petechiae are uncommon
Murine Typhus	The rash typically occurs at the end of the first week of the illness and lasts 1–4 days. It generally starts as a maculopapular eruption on the trunk and spreads peripherally, sparing the palms of the hands and soles of the feet. Rash may vary among individuals, or may be absent altogether and should not be relied upon for diagnosis.
Epidemic Typhus	The rash usually begins a couple of days after the onset of symptoms. It typically begins as a maculopapular eruption on the trunk of the body and spreads to the extremities, usually sparing the palms of hands and soles of feet. When the disease is severe, petechiae may develop. The rash may be variable among individuals and stage of infection, or may be absent altogether and should not be relied upon for diagnosis

About 25–50% of scrub typhus patients develop a rash. The rash is usually macular or maculopapular. Typically, it will begin on the abdomen of an infected individual and then spread to the extremities. Petechiae are uncommon. Murine Typhus The rash typically occurs at the end of the first week of the illness and lasts 1–4 days. It generally starts as a maculopapular eruption on the trunk and spreads peripherally, sparing the palms of the hands and soles of the feet. Rash may vary among individuals, or may be absent altogether and should not be relied upon for diagnosis. Epidemic Typhus The rash usually begins a couple of days after the onset of symptoms. It typically begins as a maculopapular eruption on the trunk of the body and spreads to the extremities, usually sparing the palms of hands and soles of feet. When the disease is severe, petechiae may develop. The rash may be variable among individuals and stage of infection, or may be absent altogether and should not be relied upon for diagnosis. 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.

Differential

Disease	Findings
Ebola	Presents with fever, chills vomiting, diarrhea, generalized pain or malaise, and sometimes internal and external bleeding, that follow an incubation period of 2-21 days.
Typhoid fever	Presents with fever, headache, rash, gastrointestinal symptoms, with lymphadenopathy, relative bradycardia, cough and leucopenia and sometimes sore throat. Blood and stool culture can confirm the presence of the causative bacteria.
Malaria	Presents with acute fever, headache and sometimes diarrhea (children). A blood smears must be examined for malaria parasites. The presence of parasites does not exclude a concurrent viral infection. An antimalarial should be prescribed as an empiric therapy.
Lassa fever	Disease onset is usually gradual, with fever, sore throat, cough, pharyngitis, and facial edema in the later stages. Inflammation and exudation of the pharynx and conjunctiva are common.
Yellow fever and other Flaviviridae	Present with hemorrhagic complications. Epidemiological investigation may reveal a pattern of disease transmission by an insect vector. Virus isolation and serological investigation serves to distinguish these viruses. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Shigellosis & other bacterial enteric infections	Presents with diarrhea, possibly bloody, accompanied by fever, nausea, and sometimes toxemia, vomiting, cramps, and tenesmus. Stools contain blood and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and blood smears, should be made. Presence of leucocytosis distinguishes bacterial infections from viral infections.
Others	Leptospirosis, viral hepatitis, rheumatic fever, and mononucleosis can produce signs and symptoms that may be confused with Ebola in the early stages of infection.

Diseases	Clinical features					Diagnosis
	Fever	Rash	Diarrhea	Cough	Specific
Ebola
Typhoid fever
Malaria
Lassa fever
Yellow fever and other Flaviviridae
Shigellosis & other bacterial enteric infections

Labs

Serologic assays are the most frequently used methods for confirming cases of scrub typhus. The indirect immunofluorescence assay (IFA) is generally considered the reference standard, but is usually not available in developing countries where this disease is endemic. Other serological tests include ELISA and indirect immunuoperoxidase (IIP) assays. Weil-Felix OX-K agglutination assays may be used in some international settings but lack sensitivity and specificity and are not generally used in the United States. These assays can detect either IgG or IgM antibodies. Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. IgG antibodies are considered more accurate than IgM, but detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness.

Because antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable confirmation of an acute scrub typhus infection. The most rapid and specific diagnostic assays for scrub typhus rely on molecular methods like polymerase chain reaction (PCR), which can detect DNA in a whole blood, eschar swab, or tissue sample. Immunostaining procedures can also be performed on formalin-fixed tissue samples. Since scrub typhus is not common in the United States, confirmatory tests are not typically available at state and local health departments; nonetheless, IFA, culture, and PCR assays can all be performed at the CDC through submission from state health departments.

Murine typhus

Rickettsia typhi can be detected via indirect immunofluorescence antibody (IFA) assay, immunohistochemistry (IHC), polymerase chain reaction (PCR) assays using blood, plasma, or tissue samples, or culture isolation. PCR is most sensitive on samples taken during the first week of illness, but prior to the start of doxycycline.

Serologic tests (typically using IFA) are the most common means of confirming murine typhus and can be used to detect either IgG or IgM antibodies. Diagnosis is usually confirmed by demonstrating a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. IgG antibodies are considered more accurate than IgM. Detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness.

Because antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable serological confirmation of an acute murine typhus infection. R. typhi antigens frequently cross-react with those of R. prowazekii and R. felis, and less often with R. rickettsii. When possible, species-specific assays for R. typhi, R. prowazekii, R. felis, and R. rickettsii should be run in parallel. IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays varies considerably based on the sample type, timing of sample collection, and the severity of disease.

Epidimic

Rickettsia prowazekii can be detected via indirect immunofluorescence antibody (IFA) assay, immunohistochemistry (IHC), polymerase chain reaction (PCR) assay of blood, plasma, or tissue samples, or culture isolation. Serologic tests are the most common means of confirmation and can be used to detect either IgG or IgM antibodies. Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. Detectable levels of IgG or IgM antibodies generally do not appear until 7–10 days after the onset of illness.

Because IgG antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable serological confirmation of an acute epidemic typhus infection. R. prowazekii antigens may cross react with those of R. typhi, and occasionally with R. rickettsii. When possible, species-specific serological assays for R. prowazekii, R. typhi, and R. rickettsii should be run in parallel. Persons with Brill-Zinsser disease generally show a rise in IgG but not IgM antibodies to R. prowazekii. IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays vary considerably based on the sample type, timing of sample collection, and the severity of disease. Since epidemic typhus is not common in the United States, testing is not typically available at state and local health departments. IFA, culture, and PCR can all be performed at the CDC, through submission from state health departments.

Epidemiology and Demographics

All age groups are at risk for rickettsial infections during travel to endemic areas. Both short and long-term travelers are at risk for infection. Transmission is increased during outdoor activities in the spring and summer months when ticks and fleas are most active. However, infection can occur throughout the year. Because of the 5- to 14-day incubation period for most rickettsial diseases, tourists may not necessarily experience symptoms during their trip, and onset may coincide with their return home or develop within a week after returning. Although the most commonly diagnosed rickettsial diseases in travelers are usually in the spotted fever or typhus groups, travelers may acquire a wide range of rickettsioses, including emerging and newly recognized species. Tickborne spotted fever rickettsioses are the most frequently reported travel-associated rickettsial infections. Game hunting and traveling to southern Africa from November through April are risk factors for African tick-bite fever, and this consistently remains the most commonly reported rickettsial infection acquired during travel. Mediterranean spotted fever infections are less commonly reported but occur over an even larger region, including (but not limited to) much of Europe, Africa, India, and the Middle East. Rocky Mountain spotted fever (also known as Brazilian spotted fever, as well as other local names) is reported throughout much of the Western Hemisphere, including Canada, the United States, Mexico, and various countries in Central and South America. Contact with dogs (in both rural and urban settings) and outdoor activities such as hiking, hunting, fishing, and camping increase the risk of infection.

Scrub typhus, which is transmitted by mites encountered in high grass and brush, is endemic in northern Japan, Southeast Asia, the western Pacific Islands, eastern Australia, China, maritime areas and several parts of south-central Russia, India, and Sri Lanka. More than 1 million cases occur annually. Most travel-acquired cases of scrub typhus occur during visits to rural areas in endemic countries for activities such as camping, hiking, or rafting, but urban cases have also been described.

R. typhi and R. felis, which are transmitted by fleas, are widely distributed, especially throughout the tropics and subtropics and in port cities and coastal regions with rodents. Humans exposed to flea-infested cats, dogs, and peridomestic animals while traveling in endemic regions, or who enter or sleep in areas infested with rodents, are at most risk for fleaborne rickettsioses. Murine typhus has been reported among travelers returning from Asia, Africa, and the Mediterranean Basin and has also been reported from Hawaii, California, and Texas in the United States.

R. akari, the causative agent of rickettsialpox, is transmitted by house-mouse mites, and circulates in mainly urban centers in Ukraine, South Africa, Korea, the Balkan states, and the United States. Outbreaks of rickettsialpox most often occur after contact with infected rodents and their mites, especially during natural die-offs or exterminations of infected rodents that cause the mites to seek out new hosts, including humans. The agent may spill over and occasionally be found in other wild rodent populations.

Epidemic typhus is rarely reported among tourists but can occur in communities and refugee populations where body lice are prevalent. Outbreaks often occur during the colder months when infested clothing is not laundered. Travelers at most risk for epidemic typhus include those who may work with or visit areas with large homeless populations, impoverished areas, refugee camps, and regions that have recently experienced war or natural disasters. Active foci of epidemic typhus are known in the Andes regions of South America and some parts of Africa (including but not limited to Burundi, Ethiopia, and Rwanda). Louseborne epidemic typhus does not regularly occur in the United States, but a zoonotic reservoir occurs in the southern flying squirrel, and sporadic sylvatic epidemic typhus cases are reported. Tick-associated reservoirs of R. prowazekii have been described in Ethiopia, Mexico, and Brazil, but documented human cases are rare.

Ehrlichiosis and anaplasmosis are tickborne infections most commonly reported in the United States. A variety of species are implicated in infection, but E. chaffeensis and A. phagocytophilum are most common. Infections with various Ehrlichia and Anaplasma spp. have also been reported in Europe, Asia, and South America. Neoehrlichia mikurensis is a tickborne pathogen that occurs in Europe and Asia. Sennetsu fever, caused by Neorickettsia sennetsu, occurs in Japan, Malaysia, and possibly other parts of Asia. This disease can be contracted from eating raw infected fish.

Physical examination

Vitals

• Fever
• Relative bradycardia with the fever.
• Tachypnea and cough

Skin

• Rash

The macular, maculopapular, or petechial rash initially occurs on the trunk and axilla and spreads to involve the rest of the body except for the face, palms, and soles. Rash may be petechial in patients with epidemic or murine typhus.

• Eschar

This is found in the scrub form of typhus and is essential in confirming a clinical diagnosis. It occurs in up to 60% of cases. Eschar occurs at the site of the arthropod bite. It starts as a painless papule, and the lesion becomes indurated and enlarged. The center of the lesion becomes necrotic and develops into a black scab. Other features

Lymph nodes

Regional lymphadenopathy Lymph nodes are often tender and enlarged. Generalized lymphadenopathy

Abdomnen

• Hepatomegaly
• Splenomegaly

HEENT

Conjunctival suffusion occurs in scrub typhus.

Medical Therapy

Typhus, louse-borne

• Louse born typhus, Rickettsia prowazekii (epidemic typhus, sylvatic typhus and Brill–Zinsser typhus

• Pathogen-directed antimicrobial therapy

• In adults

• Preferred regimen (1): Doxycycline 200 mg PO for 5 days or 2-3 days after defervescence
• Preferred regimen (2): Doxycycline 100-200 mg PO single dose in outbreak situation
• Alternative regimen: Chloramphenicol 60 to 75 mg/kg/day PO in four divided doses

• In children

• Preferred regimen (1): Doxycycline 100-200 mg PO single dose

• In pregnant women

• Preferred regimen: Doxycycline 100-200 mg PO single dose

Typhus, murine

• Murine typhus,Rickettsia typhi (flea-borne infection)

• Pathogen-directed antimicrobial therapy

• 1. Adults

• Preferred regimen : Doxycycline 100 mg PO bid continued for 3 days after the symptoms have resolved, Doxycycline 100-200 mg, PO single dose
• Alternative regimen (1): Oxacillin 2-12 g/24 hr IV q4-6h IV (maximum dose: 12 g/24)
• Alternative regimen (2): Chloramphenicol 60 to 75 mg/kg/day PO in qid

• 2. Children

• Preferred regimen: Doxycycline 100-200 mg, PO for 3-7 days
• Alternative regimen: Chloramphenicol 50-75 mg/kg/24 hr IV/PO q 6-8 hr

• 3. Pregnant women

• Preferred regimen: Doxycycline 100-200 mg, PO single dose ( late trimester)
• Alternative regimen (1): Erythromycin Base: 333 mg PO tid or estolate/stearate/ base: 250-500 mg PO qid
• Alternative regimen (2): Chloramphenicol 50 mg/kg/24 hr IV/PO q6h (maximum dose: 4 g/24 hr) (early trimester: first and second trimesters)

Typhus, scrub

• Scrub typhus, Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi- mite-borne infectious disease)

• Pathogen-directed antimicrobial therapy

• Preferred regimen (1): Doxycycline 100 mg PO/IV q12h for 3 days
• Preferred regimen (2): Chloramphenicol 500 mg PO/IV q6h
• Alternative regimen: Azithromycin 500 mg PO day 1 followed by 250 mg for 4 days

Primary Prevention

Avoid areas where you might encounter rat fleas or lice. Good sanitation and public health measures reduce the rat population. Measures to get rid of lice when an infection has been found include:

• Bathing
• Boiling clothes or avoiding infested clothing for at least 5 days (lice will die without feeding on blood)
• Using insecticides (10% DDT, 1% malathion, or 1% permethrin)

Vaccine

The first major step in the development of the vaccine was Charles Nicolle's 1909 discovery that lice were the vectors for epidemic typhus. This made it possible to isolate the bacteria causing the disease and develop a vaccine; he was awarded the 1928 Nobel Prize in Physiology or Medicine for this work. Nicolle attempted a vaccine but was not successful in making one that worked on a large enough scale.

Henrique da Rocha Lima in 1916 then proved that the bacteria Rickettsia prowazekii was the agent responsible for typhus; he named bacteria after H. T. Ricketts and Stanislaus von Prowazek, two zoologists who died investigating a typhus epidemic in a prison camp in 1915. Once these crucial facts were recognized, Rudolf Weigl in 1930 was able to fashion a practical and effective vaccine production method by grinding up the guts of infected lice that had been drinking blood. It was, however, very dangerous to produce, and carried a high likelihood of infection to those who were working on it.

A safer mass-production-ready method using egg yolks was developed by Herald R. Cox in 1938. This vaccine was used heavily by 1943.

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..

Acute kidney injury in cancer patients

Types of Acute Kidney Injury in Patients with Hematologic Cancers

Cancer-related injury

• Tumor infiltration of the kidneys
• Obstructive nephropathy related to retroperitoneal lymphadenopathy
• Lysozymuria (CMML or AML) with direct tubular injury
• Hemophagocytic lymphohistiocytosis with acute interstitial disease
• Vascular occlusion associated with DIC and hyperleukocytosis (rare)
• Hypercalcemia with hemodynamic acute kidney injury and acute nephrocalcinosis
• Glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, membranous

nephropathy, amyloidosis, immuno-tactoid glomerulonephritis, fibrillary glomerulonephritis, crescentic glomerulonephritis)

Therapy-related injury

• Nephrotoxicity (including thrombotic microangiopathy, acute tubular injury, tubulointerstitial nephritis, and glomerular disease)
• Tumor lysis syndrome with acute uric acid nephropathy (may occur spontaneously)
• Intratubular obstruction from medications (e.g., methotrexate)

Other types of injuries

• Volume depletion
• Sepsis and septic shock
• Nephrotoxicity of radiocontrast agents
• Nephrotoxicity of common medications, such as NSAIDs, ACE inhibitors,
• ARBs, and antibiotics

Cancers and association

• MM
• RCC

Types of Haemophilus influenzae Infections

H. influenzae, including Hib, can cause many different kinds of infections. These infections can range from mild ear infections to severe diseases, like bloodstream infections. When the bacteria invade parts of the body that are normally free from germs, like spinal fluid or blood, this is known as "invasive disease." Invasive disease is usually severe and can sometimes result in death.
The most common types of invasive disease caused by H. influenzae are:

• Pneumonia
• Bacteremia
• Meningitis (infection of the covering of the brain and spinal cord)
• Epiglottitis (swelling of the windpipe that can cause breathing trouble)
• Cellulitis (skin infection)
• Infectious arthritis (inflammation of the joint)

H. influenzae can also be a common cause of ear infections in children and bronchitis in adults.

Causes

• Haemophilus influenzae disease is caused by the bacterium Haemophilus influenzae.
• There are six identifiable types of H. influenzae (a through f) and other non-identifiable types (called nontypeable). The one that people are most familiar with is H. influenzae type b, or Hib.
• These bacteria live in the nose and throat, and usually cause no harm. However, the bacteria can sometimes move to other parts of the body and cause infection. Some of these infections are considered “invasive” and can be very serious and sometimes even deadly.

Incubation period

The incubation period (time between exposure and first symptoms) of H. influenzae disease is not certain, but could be as short as a few days.

Pathophysiology

Transmission

• Transmission is by direct contact or by inhalation of respiratory tract droplets.
• Neonates can acquire infection by aspiration of amniotic fluid or contact with genital tract secretions containing the bacteria.

Seeding

• A larger bacterial load or the presence of a concomitant viral infection can potentiate the infection.
• The colonizing bacteria invade the mucosa and enter the bloodstream.
• The spread of bacteria by direct extension to the eustachian tubes causes otitis media.
• Spread to the sinuses leads to sinusitis.
• Spread down the respiratory tract results in bronchitis and pneumonia.
• Eustachian tube dysfunction, antecedent viral upper respiratory tract infection (URTI), foreign bodies, and mucosal irritants, including smoking, can promote infection.
• In patients with underlying chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF), NTHi frequently colonizes the lower respiratory tract and can exacerbate the disease.

Pathogenesis

• The antiphagocytic nature of the Hib capsule and the absence of the anticapsular antibody lead to increasing bacterial proliferation.
• When the bacterial concentration exceeds a critical level, it can disseminate to various sites, including meninges, subcutaneous tissue, joints, pleura, pericardia, and lungs.
• The antibody to the Hib capsule plays the primary role in conferring immunity.
• Newborns have a low risk of infection, likely because of acquired maternal antibodies.
• When these transplacental antibodies to the PRP antigen wane, infants are at high risk of developing invasive H influenzae disease, and their immune responses are low even after the disease.
• Therefore, they are at high risk of repeat infections since prior episodes of H influenzae do not confer immunity. By age 5 years, most children have naturally acquired antibodies.
• The Hib conjugate vaccine induces protection by inducing antibodies against the PRP capsule.
• The Hib conjugate vaccine does not provide protection against NTHi strains. Since the widespread use of the Hib conjugate vaccine, NTHi has become more of a pathogen.

Natural history

• Between 3% to 6% of Hib cases in children are fatal; up to 20% of patients who survive Hib meningitis have permanent hearing loss or other long-term neurological sequelae.
• Patients ≥65 years of age with invasive H. influenzae disease (Hib, non-b, and nontypeable) have higher case-fatality ratios than children and young adults.

Epidemiology

Incidence

• Before vaccine became available in 1988, the annual attack rate of invasive Hib disease was estimated at 64-129 cases per 100,000 children younger than 5 years.
• The estimated annual incidence of Hib infection is 0.04 cases per 100,000 general population.
• The estimated annual incidence of non-Hib infection is 0.36 cases per 100,000 general population.

Gender

• Hib disease has no sexual predilection

Age

• Hib infections are rare in patients older than 6 years.
• Hib infections are most common in children aged 6 months to 6 years.

Risk factors

• Unimmunized children younger than 4 years of age, as well as household contacts and daycare classmates of a person with Hib disease are at increased risk of Hib disease.
• Close contacts of patients with non-b or nontypeable H. influenzae has not been identified.
• Patients with sickle cell disease, asplenia, HIV, and certain immunoglobulin and complement component deficiencies, as well as recipients of hematopoietic stem cell transplant and chemotherapy or radiation therapy for malignant neoplasms are at increased risk for invasive H. influenzae disease.
• Immigrants

Complications

• Complications depend on the type of invasive infection caused the bacteria.
• Meningitis can result in hearing loss.
• Bacteremia (blood infection) can result in loss of limb(s).
• Invasive H. influenzae infections can sometimes result in death. Even with antibiotic treatment, about 3 to 6 out of every 100 children with meningitis caused by Hib die from the disease.
• When H. influenzae cause a non-invasive infection, like bronchitis or an ear infection, complications are rare and typically not severe. If appropriate, antibiotics can be given to prevent complications

Medical therapy

A number of medical treatments are utilized with the goal of putting and keeping the disease in remission. These include 5-aminosalicylic acid (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), steroid medications, immunomodulators (such as azathioprine, mercaptopurine (6-MP), and methotrexate), and newer biological medications, such as infliximab (Remicade) and adalimumab (Humira).Also in January 2008 the U.S. Food and Drug Administration approved a new biological medication known as natalizumab (Tysabri) for both induction of remission and maintenance of remission in moderate and severe Crohn's Disease. Treatment is only needed for people exhibiting symptoms. The therapeutic approach to Crohn's disease is sequential: to treat acute disease and then to maintain remission. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics.

Once remission is induced, the goal of treatment becomes maintaining remission and avoiding flares. Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs. On 14 January 2008 the U.S. Food and Drug Administration approved natalizumab (Tysabri) for both induction of remission and maintenance of remission in Crohns. Natalizumab is humanized monoclonal antibody (MAb), and the first alpha-4 antagonist in a new class of agents called selective adhesion-molecule (SAM) inhibitors. Alpha-4 integrin is required for leukocytes to adhere to the walls of blood vessels and migrate into the gut; natalizumab prevents leukocytes from doing that. Natalizumab was previously approved for multiple sclerosis. However, because it suppresses the immune system, natalizumab has been linked to a very rare adverse effect that is usually fatal if undetected. Leukocytes also protect the body from viruses, and 2 patients on natalizumab, who were also receiving other immuno-suppressive drugs (Avonex and Immuran), died of a rare brain infection, progressive multifocal leukoencephalopathy. Because of this danger, patients must be in a special monitoring program, and natalizumab is given as a mono-therapy. As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.

Surgery may be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs within a reasonable time. For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel. According to a retrospective review at the Cleveland Clinic, there is no statistical significance between strictureplasty alone versus strictureplasty and resection specifically in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected patients with duodenal involvement.

Recent studies using Helminthic therapy or hookworms to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.

Pathophysiology of Sepsis

• Sepsis is defined as a collection of physiologic responses by the immune system in response to an infectious agent.
• The clinical course of sepsis depends on the type and resistance of the infectious organism, the site and size of the infecting insult, and the genetically determined or acquired properties of the host's immune system.
• The pathogenesis of sepsis can be discussed as follows

Immune system activation

• Pathogen entry and survival is facilitated by tissue contamination (surgery or infection), foreign body insertion (catheters), and immune status (immunosuppression).
• The innate immune system is activated by bacterial cell wall products, such as lipopolysaccharide, binding to host receptors, including Toll-like receptors (TLRs).
• These are widely found on leukocytes and macrophages, and some types are found on endothelial cells.
• These have specificity for different bacterial, fungal, or viral products, and genetic polymorphisms are associated with a predisposition to shock with gram-negative organisms.
• Activation of the innate immune system results in a complex series of cellular and humoral responses, each with amplification steps

Immune repsonse

• Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukins 1 and 6 are released, which in turn activate immune cells.
• Reactive oxygen species, nitric oxide (NO), proteases, and pore-forming molecules are released, which bring about bacterial killing.
• Nitrous oxide is responsible for vasodilatation and increased capillary permeability and has been implicated in sepsis-induced mitochondrial dysfunction. [4
• The complement system is activated, and mediates activation of leukocytes, attracting them to the site of infection where they can directly attack the organism (phagocytes, cytotoxic T lymphocytes), identify it for attack by others (antigen-presenting cells, B lymphocytes), "remember" it in case of future infection (memory cells, B lymphocytes), and cause the increased production and chemotaxis of more T helper cells.

The endothelium and coagulation system

• The vascular endothelium plays a major role in the host's defense to an invading organism, but also in the development of sepsis.
• Activated endothelium not only allows the adhesion and migration of stimulated immune cells but becomes porous to large molecules such as proteins, resulting in the tissue edema.
• Alterations in the coagulation systems include an increase in procoagulant factors, such as plasminogen activator inhibitor type I and tissue factor, and reduced circulating levels of natural anticoagulants, including antithrombin III and activated protein C (APC), which also carry anti-inflammatory and modulatory roles.

Inflammation and organ dysfunction

• Through vasodilatation (causing reduced systemic vascular resistance) and increased capillary permeability (causing extravasation of plasma), sepsis results in relative and absolute reductions in circulating volume.
• A number of factors combine to produce multiple organ dysfunctions.
• Relative and absolute hypovolemia are compounded by reduced left ventricular contractility to produce hypotension.
• Initially, through an increased heart rate, cardiac output increases to compensate and maintain perfusion pressures, but as this compensatory mechanism becomes exhausted, hypoperfusion and shock may result.
• Impaired tissue oxygen delivery is exacerbated by pericapillary edema.
• It makes oxygen to diffuse a greater distance to reach target cells.
• There is a reduction of capillary diameter due to mural edema and the procoagulant state results in capillary microthrombus formation.

Additional contributing factors

• Disordered blood flow through capillary beds, resulting from a combination of shunting of blood through collateral channels and an increase in blood viscosity secondary to loss of red cell flexibility.
• As a result, organs become hypoxic, even with increase blood flow.
• These abnormalities leads to lactic acidosis, cellular dysfunction, and multiorgan failure.
• Cellular energy levels fall as metabolic activity begins to exceed production.
• However, cell death appears to be uncommon in sepsis, implying that cells shut down as part of the systemic response.
• This could explain why relatively few histologic changes are found at autopsy, and the eventual rapid resolution of severe symptoms, such as complete anuria and hypotension, once the systemic inflammation resolves.