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Typhoid fever by sammyc2007

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									Infectious Diseases Case Presentation

Daniel Caplivski, M.D.

Clinical Presentation


A 20 year-old man with no past medical history presented to the emergency department with fever as high as 104 for 10 days.  He also noted chills, rigors, headache, profuse vomiting and diarrhea, and a cough productive of white sputum.  He was unable to tolerate food, because of nausea and vomiting. He reported that the diarrhea as watery without blood or mucous.

Clinical Presentation Continued
The patient had been in Indonesia from June 12th until July 16th. The onset of his symptoms was one week after his return.  He had traveled to Jakarta, West Java, and Sumatra with his family.  He was not taking anti-malarial prophylaxis, and reports eating the same food that his family ate.  No other members of his family had any symptoms.


Clinical Presentation Continued


The patient had been treated by his primary care physician with oral amoxicillin for 2 days prior to his admission with little change in his symptoms  He was born in Indonesia and had lived in the United States for 14 years.  He did not use tobacco, alcohol, or illicit drugs  He denied any previous sexual history.

Physical Exam
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     

T= 105.9 BP 106/63 P 108 R16 Sat 97%
Gen--ill appearing, no acute distress Heent--Perrl, anicteric sclera, oropharynx without lesions, but dry mucous membranes, no lymphadenopathy Neck--supple Cv--rrr S1/S2, without murmurs, rubs, or gallops Lungs--Clear to auscultation bilaterally Abdomen--soft, non-tender, nondistended, nl bs, palpable liver edge 2cm below the right costal margin, no splenomegaly Ex--no edema, no rash, 4 punctate excoriated lesions on legs which appeared to be mosquito bites.

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Laboratory Values
Na 129 WBC 7.1

K Cl HCO3 BUN Creatinine Glucose Calcium Pt/inr Ptt

3.0 90 23 12 1.4 105 7.9 13.4/1.18 41.9

Hb Hct Platelets Mcv Neut Lymphs Mono Eos Bands

14.4 41.9 96-clumped 86.6 63% 27.7% 8.9% 0.1% 3

Laboratory Values Continued
HD #1 Alk Alt Phos 25 250 Ast 122 Ggt 160 Ldh 385 tp 6.5 Alb. 2.9 t.bili d.bil 1.4 0.5

#2
#3

22
21

209
202

152
169

166
161

485
511

6.1
6.6

2.8
3.0

1.3
1.1

0.5
0.4

#4

22

173

168

168

541

6.9

2.9

1.1

0.5

Other Studies


Chest PA/Lateral Plain Film revealed no infiltrates or effusions  Urinalysis—showed no leukocyte esterase, no nitrites, no blood, and no white cells or casts  Stool—was negative for occult blood and negative for leukocytes.

Differential Diagnosis for Travelers Returning From Southeast Asia With Fever*
Arthropod Born Diseases  Malaria  Japanese Encephalitis  Dengue fever  Typhus
       

Other Infections  HIV and Other STD’s  Tuberculosis  Rabies  Leptospirosis  HBV, HCV  Plague

Food and Waterborn diseases Travelers’ diarrhea Cholera Typhoid Hepatitis A and E Poliomyelitis Schistosomiasis and other fluke infections Other viral infections (enterovirus)

*Source—Uptodate 11.1, Murdoch, David

Clinical Course


 

Pt was started on ciprofloxicin 400mg iv q12 hours for possible typhoid fever. He continued to have fever to 103 for the next 2 days. Surgery was consulted for a decrease in hemoglobin from 14.4 to 11.2 CT scan of the abdomen revealed linear defects in the spleen suspicious for lacerations, minimal pericholecystic fluid, and a thickened terminal ileum—consistent with either an infectious or inflammatory process. Enlarged lymph nodes were noted in the mid abdomen and in the right lower quadrant, measuring up to 2.5 cm.

Clinical Course, Conclusion


Hemoglobin remained stable and no surgical intervention was required  On Hospital Day #2 blood cultures were growing gram negative rods, which were later identified as pan-sensitive Salmonella typhi  The patient’s fever persisted until hospital day 4, but his vomiting and diarrhea were improved by hospital day 2. No rose spots were seen  The patient was discharged on oral trimethoprim/sulfamethoxazole after a possible drug reaction to the fluroquinolone.

Microbiology of Typhoid Fever
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

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Salmonella species are gram negative rods which can produce several different manifestations of disease (gastroenteritis, enteric fever, osteomyelitis, etc) Enteric fever is usually caused by Salmonella typhi, but can also be caused by Salmonella typhi Type B, and Salmonella paratyphi type A or C Nontyphoidal salmonella species usually present with less severe illness—most often as gastroenteritis

Enteric Fever Clinical Manifestations
Clinical Presentation  Onset of symptoms 5-21 days after ingestion  High sustained fevers  Pulse temperature dissociation  Diarrhea or Constipation  Hepatosplenomegaly  Typical rash (rose spots) that is often transient and easily missed  Invasion of the Peyer’s patches in the small bowel can lead to instestinal hemorrhage and perforation  Delerium, stupor, coma, and septic shock can be seen in advanced cases

Clinical Relapse and Chronic Carriers


Prior to the use of antibiotics, mortality from infection was thought to be 15%  Approximately 10% of patients had relapsing illness  1-4% of untreated patients became chronic carriers (Typhoid Mary)  Humans are the only reservoir for the organism, most infections transmitted via contaminated food or water.

Virulence Factors
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

 

Initial infection within the small bowel leads to dissemination of the organisms within the reticuloendothelial system. Ability of the bacteria to survive within macrophages in the bone marrow has been linked to genes that inhibit host cell protein systhesis (phoP/phoQ). Several important virulence genes also enable the pathogens to invade deeper tissues (cdt). The Vi capsular polysaccharide may have some role in pathogenesis, though deletion of this gene did not result in decreased infection in volunteer studies.

Reduction of Mortality in Chloramphenicol-Treated Severe Typhoid Fever by Dexamethasone Hoffman, et al. NEJM 1984; 31:82-8



 

In RCT of 28 patients with culture-positive typhoid fever with severe sepsis, ½ of patients were given dexamethasone (3mg/kg) and the other half placebo. Both groups received standard antimicrobial therapy and supportive care The definition of severe typhoid fever included abnormal state of consciousness (delirium, obtundation, stupor, or coma) or shock (sbp<90 with decreased organ perfusion)

Hoffman et al. Continued






Of 263 pts with typhoid fever, 42 met severity criteria of the study, 38 were included in the final analysis (4 were excluded from the study for death within 6 hours) In the placebo group 10/18 patients died, while in the dexamethasone group 2/20 patients died. 55% vs 10%, p=0.003 Including the 4 patients who died early on in the study did not affect the statistical significance of the treatment effect.

References
Reduction of Mortality in Chloramphenicol-Treated Severe Typhoid Fever By High Dose Dexamethasone. Hoffman, et al. NEJM 1984;310:82-8. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases Chapter 210 p2344-2356 Salmonella species, including Salmonella typhi Uptodate References 1. Approach to the patient with typhoid fever. Hohmann, Elizabeth 2. Pathogenesis of typhoid fever. Hohmann, Elizabeth 3. Treatment of typhoid fever. Hohmann, Elizabeth


								
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