Ms. X was born in 1869 in Cookstown, Northern Ireland. She immigrated to the United States in 1883 at the age of 15. She lived with her aunt and uncle for a time and later found work as a "----" for affluent families.

In 1901, she moved to Manhattan, where members of the family for whom she worked developed fevers and diarrhea, and the laundress died.

Ms.X then went to work for a lawyer; she left after seven of the eight people in that household became ill.

In 1906, she took a position in Oyster Bay, Long Island, and within two weeks 10 of the 11 family members were hospitalized with "---- disease". She changed jobs again, and similar occurrences happened in three more households.

She worked as a "---" for the family of a wealthy New York banker, Charles Henry Warren. When the Warrens rented a house in Oyster Bay for the summer of 1906, she went along too. From August 27 to September 3, six of the 11 people in the family came down with "---disease".

The disease at that time was "unusual" in Oyster Bay, according to three medical doctors who practiced there. Ms X, was subsequently hired by other families, and outbreaks followed her.

Ms. X :Job : Disease spread:

Mary MallonCookTyphoid Fever

Popularly known as Typhoid Mary

Salmonellosis

Dr. Jayaprakash AppajigolAssociate Professor of MedicineJN Medical College, Belgaum

Salmonellosis

• Salmonellae are gram-negative, non-spore-forming, facultatively anaerobic bacilli that measure 2–3X0.4–0.6 microns.

• Motile by means of peritrichous flagella

Salmonella contaminated Water/Food

Cross the epithelial layer of the small intestine by bacteria-mediated endocytosis (BME).

S. typhi and S. paratyphi, which cause enteric (typhoid) fever, are phagocytosed by macrophages

Salmonellae survive the antimicrobial environment of the macrophage

Typhoidal salmonellae disseminate throughout the body in macrophages via the lymphatics and colonize reticuloendothelial tissues (liver, spleen, lymph nodes, and bone marrow and GALLBLADDER)

ENTERIC (TYPHOID) FEVER

Enteric (typhoid) fever is a systemic disease characterized by fever and abdominal pain and caused by dissemination of S. typhi or S. paratyphi

Transmission: Water /food borne by fecal contamination by ill or

asymptomatic chronic carriers.Sexual transmission and among heath care workers while

handling infected specimen

Clinical Course

Incubation Period 1-2 weeksStep Ladder FeverCharacterized by a rising temperature over the course of each day that drops by the subsequent morning. The peaks and troughs rise progressively over time.

Hallmark features of this disease fever (>75%) and abdominal pain (30-40%)

First week of illness:Abdominal pain and tendernessFierce colicky right upper quadrant painConstipation that lasts the duration of the illness- due to

monocytic infiltration inflames Peyer patchesThe individual then develops a dry cough, dull frontal

headache, delirium, and an increasing malaise

Rose Spots:Develop at the end of first week.

Clinical Course

Rose Spots:Develop at the end of first week. Faint, salmon-colored, blanching, maculopapular rash located primarily on the trunk and chest. The rash is evident in ~30% of patients at the end of the first week and resolves without a trace after 2–5 days.

Clinical Course

These are bacterial emboli to the dermis and occasionally develop in persons with shigellosis or nontyphoidal salmonellosis.

Second WeekThe signs and symptoms listed above progressThe abdomen becomes distended, and soft splenomegaly is common.

Relative bradycardia and Dicrotic pulse (double beat, the second beat weaker than the first) may develop.

Clinical Course

Dicrotic pulse

Third weekFebrile individual grows more toxic and anorexic with significant weight loss

Conjunctiva congested, thready pulse, Tachypnea, crackles over lung base, more distended abdomen.

Pea soup diarrhea: foul, green-yellow, liquid diarrhea

The individual may descend into the typhoid state, which is characterized by apathy, confusion, and even psychosis

Clinical Course

Third week (Cont…)Necrotic Peyer patches may cause bowel perforation and peritonitis

At this point, overwhelming toxemia, myocarditis or intestinal hemorrhage may cause death.

Clinical Course

If the individual survives to the fourth week, the fever, mental state, and abdominal distension slowly improve over a few days. Intestinal and neurologic complications may still occur in surviving untreated individuals. Weight loss and debilitating weakness last months. Some survivors become asymptomatic S typhi carriers and have the potential to transmit the bacteria indefinitely

Clinical Course

• Neurologic manifestations occur in 2–40% of patients and include meningitis, Guillain-Barré syndrome, neuritis, and neuropsychiatric symptoms (described as “muttering delirium” or “coma vigil”), with picking at bedclothes or imaginary objects.

• Rare manifestationsDisseminated intravascular coagulation, hematophagocytic syndrome, pancreatitis, hepatic and splenic abscesses and granulomas, endocarditis, pericarditis, myocarditis, orchitis, hepatitis, glomerulonephritis, pyelonephritis and hemolytic-uremic syndrome, severe pneumonia, arthritis, osteomyelitis, and parotitis.

Clinical Course-Less common

The bacteria infect the gallbladder via either bacteremia or direct extension of infected bile. The result is that the organism re-enters the gastrointestinal tract in the bile and reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the stool and are then available to infect other hosts.

Clinical Course-Chronic Carriers

Up to 10% of untreated patients with typhoid fever excrete S. typhi in the feces for up to 3 months, and 1–4% develop chronic asymptomatic carriage, shedding S. typhi in either urine or stool for >1 year. Chronic carriage is more common among women, infants, and persons who have biliary abnormalities or concurrent gallbladder infection with Schistosoma haematobium

Clinical Course-Chronic Carriers

InvestigationsThe definitive diagnosis of enteric fever requires the isolation of S . typhi from blood, bone marrow, other sterile sites, rose spots, stool, or intestinal secretions

The sensitivity of blood culture is only 40–80%, probably because of high rates of antibiotic use in endemic areas and the small quantities of S. typhi present in blood. Early culture results can be obtained by culturing buffy coat rather than whole blood.

Bone marrow culture is 55–90% sensitive, and, unlike that of blood culture, its yield is not reduced by up to 5 days of prior antibiotic therapy.

• Stool cultures, while negative in 60–70% of cases during the first week, can become positive during the third week of infection in untreated patients.

• Several serologic tests, including the classic Widal test for “febrile agglutinins,” are available

• PCR and DNA probe assays to detect S. typhi in blood have been identified but have not yet been developed for clinical use.

Investigations

BASUB- Blood Culture S- Stool CultureA- Agglutinin Test U- Urine Culture

Treatment of Enteric (Typhoid) Fever

Prompt administration of appropriate antibiotic therapy prevents severe complications of enteric fever and results in a case fatality rate of <1%.

Dexamethasone in Typhoid Fever

38 Culture proven Typhoid Fever patient who are critically ill (shock or confusion)

20 patients, 3mg/kg dexamethasone iv,

followed by 1mg/kg 6th Hrly/iv for eight doses +

Chloramphenicol

18 patients, placebo+ Chloramphenicol

2 patients died 10 patients died

Jakarta IndonesiaNew England Journal of Medicine 1984 Jan 12;310(2):82-8.

1. Ty21a, an oral live attenuated S. typhi vaccine (given on days 1, 3, 5, and 7, with a booster every 5 years); and

2. Vi CPS, a parenteral vaccine consisting of purified Vi polysaccharide from the bacterial capsule (given in 1 dose, with a booster every 2 years).

Prevention- Vaccines

Continuing the Mary’s storyFirst quarantine (1907–10)

Release and second quarantine (1915–38)

Mallon spent the rest of her life in quarantine at the Riverside

Hospital. Six years before her death, she was paralyzed by a

stroke. On November 11, 1938, she died of pneumonia at age 69. An autopsy found evidence of live typhoid bacteria in her gallbladder.

Mallon was the first asymptomatic typhoid carrier to be identified by medical science

Salmonellae are gram-negative bacteria with peritrichous Flagella

Water /food borne by fecal contamination by ill or asymptomatic chronic carriers.

Enteric (typhoid) fever is a systemic disease characterized by fever and abdominal pain

Step Ladder Fever, Rose spots, Dicrotic Pulse, ileal perforation and sepsis are the classical presentations

Typhoid Fever- Conclusions

Chronic carrier state can develop by infecting Gallbladder

The definitive diagnosis of enteric fever requires the CULTURE of S . typhi from blood, bone marrow, other sterile sites, rose spots, stool, or intestinal secretions

Quinolones and Third Generation Cephalosporins are effective

Effective Vaccines are available

Typhoid Fever- Conclusions

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Appajigol