4/16/2013. Curriculum Vitae. Khie Chen

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1 Curriculum Vitae Name : Lie Khie Chen Birth : Jakarta Graduates MD : FKUI 1994 Internist : FKUI 23 Consultant : FKUI 26 Occupation Internal Medicine Department Tropical Medicine and Infectious Diseases Division Interest Sepsis Antimicrobial Treatment Antimicrobial Resistance Fungal Infection HIV and opportunistic infections Update on Pathogenesis and Management of Typhoid fever Khie Chen Division of Tropical Medicine and Infectious Diseases Departement of Internal Medicine Medical Faculty Univesity of Indonesia Dr. Cipto Mangunkusumo General Hospital Jakarta Typhoid Fever Typhoid fever is an acute systemic infection caused by Salmonella enterica serotype typhi or paratyphi which is also known as Salmonella typhi 1

2 Epidemiologic Distribution of Typhoid Fever Some example of commonly Occuring Salmonella serotypes and groups Group A B C D Serotype S. paratyphi A S. paratyphi B S. stanley S. saintpaul S. agona S. typhimurium S. paratyphi C S. choleraesuis S. virchow S. thompson S. typhi S. enteritidis S. dublin S. gallinarium Pathogenesis Contaminated food of drinks Gastric acid Bowel lumen Mucosal defence Adhesion to mucose Colonization Invation to Peyer Patch Regional Lymphadenitis Thoracic duct 1 st systemic bacteriemia 2

3 Pathogenesis Infection of RE system Liver, Spleen 2 nd Bacteriemia Gall bladder Lung, Myocard Kidney, etc Feces Reinfection in bowel mucose Systemic manifestation Hyperplasia Peyer Patch Inflammation, erosion Bleeding, perforation Salmonella Pathogenesis First : ATTACHMENT Second : MUCOSAL INVASION Jade 28 Attachment Type 1 Fimbriae fim Long Polar Fimbriae lpf Plasmid-Encoded Fimbriae pef Thin Aggregative Fimbriae agf 3

4 fim, lpf, pef genes Type 1 fimbriae specifically bind -D-mannose receptors on various eucaryotic cell types LP fimbriae mediate adhesion to the cells of the Peyer's patches of the small intestine in a mouse model of infection S. typhimurium, S. enteritidis, S. choleraesuis, and S. paratyphi C, contain pef sequences. PE fimbriae can adhere to histological sections of murine small intestine more effectively Jade 28 Agf gene Thin aggregative fimbriae (3 to 4 nm wide) (curli) were identified and purified from S. enteritidis Curli-producing bacteria tend to autoaggregate, a phenomenon which has been suggested to enhance the survival of salmonellae facing hostile barriers such as stomach acid or other biocides they may encounter Mucosal Invation The mechanisms of Salmonella invasion, that is, the stimulation of nonphagocytic cells to internalize bacteria, are clearly complex. Salmonella pathogenicity island 1 (SPI1), is believed to have been acquired by horizontal transfer from another pathogenic bacterial species during its evolution 4

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6 Clinical Picture Fever Headache malaise myalgia nausea abdominal discomfort constipation diarrhea dry cough epistaxis confusion, delirium psychosis convulsion coated tongue bradicardia relative tender abdomen hepatomegaly splenomegaly rose spots erythmatous muco papular lesion Fever pattern in Typhoid Fever High fever Headache Abdominal discomfort Diarrhea or constipation Relative bradicardia Leucopenia Mild thrombocytopenia Relative neutrofilia Aneosinofilia

7 Fever pattern : typhoid fever Typhus Inversus Pattern Lowest early in the morning Highest about.3 to 6.3 pm Can be found in typhoid fever tuberculosis Pulse Temperature dissosiation In normal temperature 37 o C (99 o F) pulse 8 beats/min Increased 9 beats/min every 1 o F Relative bradicardia can be found in enteric/typhoid fever mycoplasma, malaria falciparum Devervescence : 3-7 days after treatment usually on 2 nd or 3 rd weeks Female 31 yo, fever since 2 weeks ago Hb 9.3 L 16 Ht 28 Tr 17. Diff -/1/4/62/31/2 ESR 6 CRP 68 Widal ty O 1/16 H >1/64 ty B H 1/16 Treatment : Ceftriaxone 3g/day Gall culture - PCR S typhi + Clinical Presentation of Typhoid Fever Clinical sign and symptom sum (n=119) % Headache Epigastric pain Nausea Anorexia Fever (>37.2) Muscular pain Rigor Coated tongue Vomiting Cough Relative bradicardia Diarrhea Constipation Hepatomegaly Splenomegaly Pohan HT, Indones J Int Med 24;36(2) 7

8 Clinical scoring scale for typhoid fever Fever < 1 wk 1 Headache 1 Weakness 1 Nausea 1 Anorexia 1 Abdominal pain 1 Vomiting 1 Disturb GI motility 1 Insomnia 1 Hepatomegaly 1 Spelenomegaly 1 Fever > 1 wk 2 Relative bradicardia 2 Typhoid tongue 2 Melena stools 2 Impaired consciousness 2 Clinical typhoid fever if score > 13 of maximal 2 Adapted from : Nelwan RHH. Conns Current Traatment 23 Laboratory Examination Peripheral blood count Serum transaminase Albumin Serology Blood culture PCR leucopenia, leucocytosis normal WBC count mild anemia thrombocytopenia increased ESR increased ALT and AST hypoalbuminemia Increased titer of aglutinin O, H and Vi Salmonela typhi positive Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Distribusi Seroprevalensi Uji Widal persentase S. typhi S. pth A S. pth B S. pth C Widal O Widal H Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 26 8

9 Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Distribusi Titer Widal S. Thypi O dan H (n : 3) persentase >128 Widal S. Thypi O Widal S. Thypi H Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 26 Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Distribusi Titer Widal S. parathypi A persentase Widal S. parathypi A O Widal S. parathypi A H >128 Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 26 Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Distribusi Titer Widal S. parathypi B Widal S. parathypi B O Widal S. parathypi B H >128 Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 26 9

10 Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Distribusi sebaran serologi Widal S. parathypi C (n : 3) persentase Widal S. parathypi C O Widal S. parathypi C H >128 Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 26 Blood culture and PCR results in diagnosis of Typhoid Fever Treatment Non Pharmacologic : Bed rest, Nutrition Pharmacologic Symptomatic Antibiotic : Ampicillin/Amoxicillin 2x7 or 3x mg Chloramphenicol 4xmg Cephalosporin : Ceftriaxone 3-4 g/days Fluoroquinolones : Ciprofloxaxin 2x mg Ofloxacin 2x4 mg Pefloxacin 1x4 mg Fleroxacin 1x mg Levofloxacin 1xmg 1

11 South East Asia J Trop Med Pub Health 26; 37 (1):126 Complications Intestinal complication intestinal perforation gastrointestinal hemorrhage hepatiitis, pancreatitis, paralytic ileus Extraintestinal Cardiovascular : shock, myocarditis Neuropsychiatric : encephalopaty, delirium psychosis Respiratory : bronchitis, pneumonia, pleuritis Hematology : anemia, DIC Kidney : glemerulonephritis, pyelonephritis Others : osteomyelitis, focal abscess 11

12 Carrier State Exist of S. typhi in feces or urine without clinical manifestation 1 year after recovery from typhoid fever S. typhi still be found in feces of urine 2 or 3 months after recovery in 16% patients Impairment of host defence mechanism, gall and kidney stone, chronic gall and kidney infection contribute in pathogenesis of carrier state Carrier State Diagnosis of carrier state : feces and urine culture, Vi antibody Treatment : Without gall stone : Ampicillin, Amoxicillin, Cotrimoxazole With gall stone : Cholecystectomi and treatment with Ciprofloxacin or Norfloxacin With Schistosomiasis : Eradication of schistosomiasis before treatment of carier state Prevention Avoid risky food or drinks Hand washing Vaccination Detection of carrier state in food handler 12