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J i t Clinical Joint Cli i l M Meeting ti A Case of fever January 2008 Dr. Cheng Hei Wan Lian NDH 1 HKCEM_JCM_NDH 2 Jan 2008 D Demographic hi d data t 38/F | Indonesian Maid | Working g in Hong g Kong g for 5 yyears | c/o fever x 2/7 | 2 HKCEM_JCM_NDH 2 Jan 2008 At triage ti Ambulatory | Alert & conscious | Temp p 39.2̓C | BP 124/80, P 106 | RR 16 S SpO2 O2 98% ((room air) i) | 3 HKCEM_JCM_NDH 2 Jan 2008 H How tto approach h thi this patient? ti t? History | Physical Examination | Investigation g | Treatment | 4 HKCEM_JCM_NDH 2 Jan 2008 Hi t ? History? | Chief complaint z | Fever Any other history ? Fever z Headache z Vomit & Vomitus details z Associated symptoms y p z Travel history z Past medical history z 5 HKCEM_JCM_NDH 2 Jan 2008 Fever | Definition Oral temp :> 37 37.5 5̓C C z Anal/ tympanic temp: > 38̓C z | Grading Low grade 37.3 – 38̓C z Moderate grade: 38-39̓C z High g g grade: 39.1-41̓C z Hyperthermia fever > 41̓C z 6 HKCEM_JCM_NDH 2 Jan 2008 Continuous Temp varies < 1’C over several days Pneumoia, UTI, typhus Biphasic Recurs only once Dengue, l leptospirosis i i Relapsing Recurrent over days or weeks Malaria, lymphoma Remittent Temp do not return to normal each day TB, endocarditis, TB endocarditis typhoid Intermittent Elevated temp for some Abscess, malaria hours of the day Pulse-temp Pulse slower than Typhoid dissociation normal temperature rise rickettsia 2 Jan 2008 HKCEM_JCM_NDH 7 F Fever pattern tt Every 24 hrs 8 Every 36 hrs HKCEM_JCM_NDH Variable 2 Jan 2008 Hi t History | | | | | | | | | | 9 Diffuse headache headache, myalgia & malaise Vomiting > 10 times, undigested food and fluid N abdominal No bd i l pain/ i / di diarrhea h No LOC/seizure/ HI No URI symptoms No urinary symptoms or PV discharge No rash No bite/ sting g TOCC –ve Unremarkable past health HKCEM_JCM_NDH 2 Jan 2008 Ph i l E Physical Examination i ti | | | | | | | 10 Temp (tym) 39.2̓C Non to toxic ic looking BP 124/80, P 106, Hydration fair No LN, no skin rash/lesion HS dual dual, no murmur RR 16 Chest clear Abdomen soft, non-tender, no mass HKCEM_JCM_NDH 2 Jan 2008 Ph i l E Physical Examination i ti | | | | 11 Alert neck soft, no stiffness C Cranial nerves grossly normal Motor & sensoryy normal Fundi no papilloedema HKCEM_JCM_NDH 2 Jan 2008 I Investigation ti ti in i A&E? WBC 5.6 | Neu 81.3%, Lym 13.6% | Hb 13.2,, Plt 296 | RLFT, albumin normal | Amylase A l 265 | CXR clear lung g field, no hilar mass | Urine multistix WBC 2+ | 12 HKCEM_JCM_NDH 2 Jan 2008 CXR 13 HKCEM_JCM_NDH 2 Jan 2008 Diff Differential ti l di diagnosis i Gastroenteritis | Flu | Genitourinary y causes e.g. g UTI/ PID | Meningitis/ encephalitis | Systemic S t i infection i f ti | 14 HKCEM_JCM_NDH 2 Jan 2008 Diff Differential ti l di diagnosis i | | ? UTI Pyuria y UTI Urethritis TB Renal or bladder calculi Glomerulonephritis Chemical cystitis Contamination ( false +ve) Pelvic appendicitis 15 HKCEM_JCM_NDH 2 Jan 2008 M Management t | Antipyretic | ?Discharge home | ?Admit observation room | ?Admit to medical unit 16 HKCEM_JCM_NDH 2 Jan 2008 Progress Admitted to observation room | Treatment: T t t | z panadal, gravol, oral Augmentin Fluctuating temp, up to 39.6̓C | Still p persistent headache with malaise | Vomited once | | 17 How will you manage this patient? HKCEM_JCM_NDH 2 Jan 2008 P Progress D2/D3 | | | | | | 18 Admitted to Medical ward Initial ddx : fever/ ? URTI IV Augmentin started Still persistent Fever+ Nausea & vomiting What a further u e Investigation es ga o ? ( D5 fever) HKCEM_JCM_NDH 2 Jan 2008 F th Investigation Further I ti ti ESR 42, CRP<1 | NPA –ve ve, sputum AFB smear –ve ve | MSU | moderate no no. of WBC ( 10,000-100,000), 10 000 100 000) z insignificant growth z EMU AFB -ve | Blood C/ST –ve | Malaria, widal test –ve | CT brain performed | 19 HKCEM_JCM_NDH 2 Jan 2008 CT brain b i 20 HKCEM_JCM_NDH 2 Jan 2008 P Progress D4 Fever persisted, up to 40̓C | Headache, nausea & vomiting | Vomiting g 1-2 times p per day, y, fluid | Whatt other Wh th ddx? dd ? | What other investigation? g | 21 HKCEM_JCM_NDH 2 Jan 2008 M i iti Meningitis | Neck stiffness | Kernig’s sign z | Brudzinski’s sign z 22 Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed. HKCEM_JCM_NDH 2 Jan 2008 23 HKCEM_JCM_NDH 2 Jan 2008 Wh t other What th iinvestigation? ti ti ? | Lumbar puncture on D4 z z z z z z z | 24 Opening pressure ( 10cm) CSF color ( clear CSF) C ll count, Cell t gram stain t i Protein. Glucose C/St ZN stain, C/St, t i AFB culture, lt Cryptococcus H Herpes simplex/ i l / varicella i ll zoster t Blood glucose HKCEM_JCM_NDH 2 Jan 2008 M i iti Meningitis | | | | | | | 25 Any empirical A i i l ttreatment? t t? COC guideline on Antibiotic use in A&E ( July 2007) Cefotaxime ( Claforan) 2g OR Ceftriaxone ( Rocephin) 2g HAHO CPG o Antibiotics use Penicillin G 4MU q4h IV and Cefotaxime 1.5-2g 1 5 2g q4h IV OR Ceftriaxone 2g q12h IV HKCEM_JCM_NDH 2 Jan 2008 E ii lT Empirical Treatment t t | Started on IV Rocephin T cover for To f suspected t d meningitis i iti and d persistent fever 26 HKCEM_JCM_NDH | 2 Jan 2008 CSF results lt 27 HKCEM_JCM_NDH 2 Jan 2008 •Glucose (spot) 6.1 28 HKCEM_JCM_NDH 2 Jan 2008 S what So h t is i your opinion i i ? Bacterial | ? Viral | ? TB | ? Fungal | 29 HKCEM_JCM_NDH 2 Jan 2008 CSF results lt 30 HKCEM_JCM_NDH 2 Jan 2008 P Progress(D6) (D6) CSF reviewed ÆZN –ve | Started St t d Pen P G/ Claforan Cl f & IV acyclovir l i | SR : compatible with TBM | Acyclovir off | Started anti-TB treatment | Notification to DH | Transferred to IT ward | 31 HKCEM_JCM_NDH 2 Jan 2008 St d d treatment Standard t t t for f TB Which drugs would you start? z Duration D ti off anti-TB ti TB medication di ti z 32 HKCEM_JCM_NDH 2 Jan 2008 Extrapulmonary TB TBM Treatment 3HRZE+/-S Æ 9HR+/-E Miliary 3HRZ + (E or S)Æ 9HR+/-E 9HR+/ E B Bone & jjoints i 2HRZ + (E or S)Æ10HR Lymphendenitis (cervical) 2HRZ + (E or S) Æ4HR Pericarditis, Pericarditis Same as uncomplicated PTB peritonitis, GU tract Total 9 months 33 HKCEM_JCM_NDH 2 Jan 2008 Progress Fever downward trend | Complicated with deranged LFT due to anti-TB medication | Titration of medication | CSF broth culture showed AF bacilli (D19) | 34 HKCEM_JCM_NDH 2 Jan 2008 TB drug d related l t dH Hepatoxicity t i it | Isoniazid, rifampicin, pyrazinamide, | Prar-aminosalicylic y acid,, prothionamide & ethionamide 35 HKCEM_JCM_NDH 2 Jan 2008 Progress Found increased vomiting after antiTB med d | GCS 15/15 | Managed conservatively | Treated as S/E of anti-TB anti TB med | Vomiting gradually subsided | 36 HKCEM_JCM_NDH 2 Jan 2008 Progress Developed vomiting again D 25 of antiTB tiTB med d | 2-3 times per day | CT brain repeated 3 days later | 37 HKCEM_JCM_NDH 2 Jan 2008 CT brain b i 38 HKCEM_JCM_NDH 2 Jan 2008 CT brain b i 39 HKCEM_JCM_NDH 2 Jan 2008 H d Hydrocephalus h l Headache, neck pain | Nausea, vomiting | Blur vision,, diplopia p p ((6th nerve p palsy) y) | Gait disturbance | Drowsiness D i | Cognitive g disturbance | Papilloedema | 40 HKCEM_JCM_NDH 2 Jan 2008 H d Hydrocephalus h l | Pathophysiology Communicating z Non-communicating z | 41 Causes for hydrocephalus? HKCEM_JCM_NDH 2 Jan 2008 H d Hydrocephalus h l iin TBM Bacteraemia seeding in meninges | Ruptured into subarachonoid space | Reactive thick exudates formed | Adhesion in basal cistern Æ hydrocephalus | Or obstruction of arachnoid granulation | 42 HKCEM_JCM_NDH 2 Jan 2008 Progress Transferred to Neurosurgical unit | Dexamethazone IV started | Repeat p CT brain Æ no interval change g | Transferred back to NDH 1 week later | Sputum S t C/St & EMU – mycobacterium b t i tuberculosis | 43 HKCEM_JCM_NDH 2 Jan 2008 L t t Progress Latest P Transfer to WTS hospital for TB bed | Continued on anti-TB medication titration | LFT improved | Patient discharged and returned back to Indonesia | 44 HKCEM_JCM_NDH 2 Jan 2008 Tuberculosis 45 HKCEM_JCM_NDH 2 Jan 2008 TB in i H Hong K Kong Important infectious disease in HK | Notification N tifi ti rate t ~6000 6000 tto 7000 per year | 10 ti times hi higher h th than western t developed countries | Listed by WHO as intermediate burden of TB | Lifetime risk 1 in every 13 persons | 46 HKCEM_JCM_NDH 2 Jan 2008 Total no. in 2006 : 5856 47 HKCEM_JCM_NDH 2 Jan 2008 T Transmission i i Air-borne transmission | Through Th h cough, h sneeze, speaks k | Chance of infection | z | Only 1 in 10 patients Æ full blown TB z | 48 Immunity, virulence, duration of exposure 50% of them develop p disease within first 2 years Death rate ~ 4-5 % HKCEM_JCM_NDH 2 Jan 2008 Cli i l ffeatures Clinical t In Hong Kong | 90% involve lungs | 1/3 of them smear positive p | z | 2/3 smear negative ~ 25% extrapulmonary TB Commonest site: LN & pleural z Other common sites: meninges. brain z 49 HKCEM_JCM_NDH 2 Jan 2008 Cli i l ffeatures Clinical t | Constitutional symptoms z non-specific Fever,, weight g loss,, night g sweat,, malaise | Cough, Cough haemoptysis | Symptoms according to site of i f ti infection | 50 HKCEM_JCM_NDH 2 Jan 2008 Di Diagnostic ti ttests t | Tuberculin skin test Detection of TB infection z Delayed hypersensitivity reaction to tubercle bacillus z | Laboratory test Sputum, urine for smear & culture z Tissue Ti for f histology hi t l z Tissue fluid e.g. CSF z 51 HKCEM_JCM_NDH 2 Jan 2008 NTEC Pharmacy Bulletin Issue 16 Apr 2004 M t Mantoux Test T t | PPD Tuberculin purified protein derivative z Sterile preparation from precipitate of heat treated M Tuberculosis or bovis z | 52 Previous P i iinfection f ti with ith mycobacterium b t i Æ delayed hypersensitivity reaction Æ reexposure to antigen ( ii.e e PPD) Æ mount host immune system Æ skin induration HKCEM_JCM_NDH 2 Jan 2008 NTEC Pharmacy Bulletin Issue 16 Apr 2004 M t Mantoux test t t | | | | | Intradermal injection of 0.1 ml PPD To volar side of forearm Look for a round wheal 8-10mm diameter Read at 48 to 72 hours ( 96hrs for elderly) Positive reactionÆ induration 10mm 53 HKCEM_JCM_NDH 2 Jan 2008 R Results lt | Interpret as Positive if patient has: Large TST reaction z BCG long time ago z From area with high prevalence of TB z Known TB contact z 54 HKCEM_JCM_NDH 2 Jan 2008 TST reaction ti Size of >=5mm induration Consider |HIV positive for |Close contacts |Hx of TB 55 >=10mm >=15mm |Foreigner |People income with no risk f t factors for f |Residential TB facilities |Immunocompromised |< 4 years old |Low HKCEM_JCM_NDH 2 Jan 2008 I t Interpretation t ti False Positive | Infection with non-tuberculous mycobacteria | Vaccination with BCG | 56 HKCEM_JCM_NDH 2 Jan 2008 I t Interpretation t ti | False negative 15-20% z Test error/anergy z Old age, high fever, steroid, immunosuppressant, hematological disease, HIV, recent viral infection, immature immune system ( < 6mths) z 57 HKCEM_JCM_NDH 2 Jan 2008 T t Treatment t Pulmonary tuberculosis Treatment Uncomplicated 2HRZ + (E or S) Æ4HR Retreatment 3(4)HRZES Æ 6(5)HR +/-E H isoniazid; R H, R, rifampicin; S S, streptomycin streptomycin, E E, ethambutol; Z Z, pyrazinamide 58 HKCEM_JCM_NDH 2 Jan 2008 Extrapulmonary TB TBM Treatment 3HRZE+/-S Æ 9HR+/-E Miliary 3HRZ + (E or S)Æ 9HR+/-E 9HR+/ E B Bone & jjoints i 2HRZ + (E or S)Æ10HR Lymphendenitis (cervical) 2HRZ + (E or S) Æ4HR Pericarditis, Pericarditis Same as uncomplicated PTB peritonitis, GU tract Total 9 months 59 HKCEM_JCM_NDH 2 Jan 2008 P d i l reaction Paradoxical ti Temporary exacerbation of TB symptoms and lesions after treatment | At least 2 weeks after treatment | Initially I iti ll shown h iimprovementt tto treatment | More common in | Extrapulmonary p y TB z Disseminated TB z 60 HKCEM_JCM_NDH 2 Jan 2008 M ltid Multidrug resistant i t t TB MDR-TB | Resistance to at least both isoniazid & rifampicin in vitro | 3.2% of world new TB cases | 1% in HK | Inadequate drug prescribed | Poor drug compliance | 61 HKCEM_JCM_NDH 2 Jan 2008 Ri k ffactor Risk t High index of suspicions | Hx of incomplete treatment | Close contact with MDR-TB patients p | Endemic area | 62 HKCEM_JCM_NDH 2 Jan 2008 T t Treatment t According to drug sensitivity | 5-6 drugs for 6 months | Followed by y 3-4 drugs g | Total duration 18 months | | 63 Quinolones/ aminoglycosides HKCEM_JCM_NDH 2 Jan 2008 E t Extensively i l drug d resistance i t TB XDR-TB | Resistance to 1st line & some 2nd line drug | 1st line : at least isoniazid & rifampicin z 2nd line: any fluroquinolones and any 1 of the 3 injectable (capreomycin, kanamycin and amikacin) kanamycin, amikacin), z 64 HKCEM_JCM_NDH 2 Jan 2008 XDR TB XDR-TB Speed of transmission probably no diff difference tto allll fforms off TB | Incidence is rare at this stage | Variable treatment outcome | Depends on drug resistance z Disease severity z Own immune system z 65 HKCEM_JCM_NDH 2 Jan 2008 I f ti Infectious Control C t l Measures M NTEC guidelines, June 2007 | HA task force in Infection Control | TB in HCW : 29-57 cases p per yyear ( DH figure) | 66 HKCEM_JCM_NDH 2 Jan 2008 S Suspected t d TB case Airborne infection isolation room | Continue airborne isolation ( CDC 2006) | Till 3 consecutive negative g AFB sputum smears collected z Or another diagnosis is made z 67 HKCEM_JCM_NDH 2 Jan 2008 C fi Confirmed d TB di disease Smear positive PTB | Airborne isolation until | Received anti-TB drug g for minimum 2 weeks AND z Demonstrated clinical improvement z | MDR-TB z 68 Till sputum t smear show h seroconversion i HKCEM_JCM_NDH 2 Jan 2008 N i f ti Non-infectiousness | Smear –ve/ extrapulmonary TB z | Smear +ve z | Non-infectious Complete 2 weeks of chemotherapy + clinical improvement MDR-TB z S t Sputum smear conversion i Tuberculosis Manual, 69 Tuberculosis and Chest2 JanService 2008 HKCEM_JCM_NDH Public Health Services Branch St ff Precautions Staff P ti | | | | 70 High risk procedure Æ N95 mask O chemotherapy On h th and d improving i i --> Surgical mask Wear gloves when handling infectious material e.g. sputum Patients utilizing investigation facilities e.g. g to x-rayy should wear surgical g mask HKCEM_JCM_NDH 2 Jan 2008 C t t tracing Contact t i | | 71 Patients z Required R i d off HIV positive iti z < 1 year old with contact with infectious case > 8 hours in same ward z Expose p to p patient with strong g smear +ve Staff z FU needed if carried out high risk procedure without airborne precautions HKCEM_JCM_NDH 2 Jan 2008 HCW with ith Si Significant ifi tC Contact t t Monitor symptoms | FU CXR annually for 2 yrs | Limited role in Terbeculin skin test Æ high background positive rate | 72 HKCEM_JCM_NDH 2 Jan 2008 Thank You 73 HKCEM_JCM_NDH 2 Jan 2008