Melioïdosis Faculty of Medical Sciences 8 October 2006 Dr Valy KEOLUANGKHOT Clinical Coordinator Mahosot-IFMT.

MMeelioïdoslioïdosisisFaculty of Medical SciencesFaculty of Medical Sciences

8 October 20068 October 2006

Dr Dr ValyValy KEOLUANGKHOT KEOLUANGKHOT

Clinical Coordinator Mahosot-IFMTClinical Coordinator Mahosot-IFMT

Introduction (1)Introduction (1) First reported in a Burmese patient in 1912 by First reported in a Burmese patient in 1912 by

A.Whitmore and C.S.KrishnaswamiA.Whitmore and C.S.Krishnaswami 11937, 937, First clinical First clinical cascasee ofof cervical cervical MMeelioidoslioidosisis

rreeportporteded inin Vietnam; > 400 Vietnam; > 400 French and US soldiers French and US soldiers infectedinfected during the during the VietnamVietnam War War ..

1949, 1949, eepidpideemicmic in in sheepsheep inin Australi Australiaa (Winton) (Winton) and and 11stst cliniclinicalcal h humanuman cas case ine in Townsville Nor Townsville Northth of of QueenslandQueensland. .

1955, 11955, 1stst clini clinical cal cascasee r reportedeported ininThaïlande Thaïlande withwith estimated 2000-3000 casestimated 2000-3000 caseses / /yearyear..

In In 1975, 1975, 11stst rreeportporteded inin France France in Zoo fromin Zoo from corpse of corpse of Prejwalski Prejwalski horse horse imported from Asiaimported from Asia

Introduction (2)Introduction (2) 1999, 11999, 1st st cliniclinicalcal cas casee

rreeportporteded inin Lao Lao P.D.R P.D.R ((IDW, IDW, Mahosot) inMahosot) in a a female farmer, 44 years female farmer, 44 years old old

No particular underlying No particular underlying disease with Fdisease with F°> 1 month, °> 1 month, alteration of General St., alteration of General St., productive cough productive cough associassociatedated with acute with acute bilateral supra-clavicular bilateral supra-clavicular lymphadenitislymphadenitis

Photo by Wellcome Trust- Mahosot Hospital-Oxford Tropical Medicine

Research Collaboration

Introduction (3)Introduction (3) Systemic zoonotic infection caused by Gram-Systemic zoonotic infection caused by Gram-

negative. bacillus : negative. bacillus : Burkholderia pseudomalleiBurkholderia pseudomallei Endemic in SE Asia & Northern territories of Endemic in SE Asia & Northern territories of

AustraliaAustralia

Transmission : air (aerosol), skin abrasionsTransmission : air (aerosol), skin abrasions

Reservoir : surface waters, soil, mud, paddy Reservoir : surface waters, soil, mud, paddy fields.fields.

Main risk factors : rice farmers, DM, chronic Main risk factors : rice farmers, DM, chronic kidney failure, thalassemia, steroid intake.kidney failure, thalassemia, steroid intake.

Introduction (4)Introduction (4) Infection is rural and seasonal : during the Infection is rural and seasonal : during the

monsoonmonsoon Common Common communcommuniitty-acquired infection y-acquired infection CClinilinicalcal mmanifestationanifestationss vary from chronic or vary from chronic or

localilocalized infection to acute disseminated infection zed infection to acute disseminated infection (severe (severe septicsepticeemimia or fulminant disease)a or fulminant disease)

Difficult to diagnose: The greatDifficult to diagnose: The great clinical mimickerclinical mimicker High relapse frequency High relapse frequency ~~ 15% / year ; 15% / year ; ~~ 40% 40%

inpatient mortalityinpatient mortality No vaccine availableNo vaccine available

EEtiologtiologyy

B pseudomalleiB pseudomallei : : environmental environmental saprophytic bactsaprophytic bacteeririaa

Gram nGram neegatigative bve bacillacillusus bipolabipolar staining (safety r staining (safety pin)pin)

Mobile, aMobile, aeerobirobicc, catalase , catalase and and oxidase (+)oxidase (+)

EEpidpideemiologmiology (1)y (1) Worldwide Worldwide DistributionDistribution // tropical tropical latitude 20° latitude 20°

NorNorthth andand 20° S 20° South outh / N/ NE E ThailandThailand + + No Northrth of of AustraliAustraliaa..

ProblProbleem m of of publipublic health c health : 1 : 1stst cause cause of of community-acquiredcommunity-acquired septica septicaeemimia ina in NE NE Thailand Thailand andand Darwin Darwin

BactBacteeririaa saprophyte saprophyte : soil, surface water.: soil, surface water. Arabinose(+) : non pathogArabinose(+) : non pathogeennic ic Arabinose(-) pathogArabinose(-) pathogeennicic RReeservoir : servoir : soilsoil

Source : A.Cheng et B.Currie: Clinical Microbiology Review, April 2005, vol 18 N°2

EEpidpideemiologmiology (2)y (2) Transmission : trans-cutanTransmission : trans-cutaneouseous (inoculation), (inoculation),

inhalation inhalation All aAll age / 40-60 ge / 40-60 yearsyears ; sex ratio Male: Female = 3:2 ; sex ratio Male: Female = 3:2 Seasonal disease: Seasonal disease: monsoonmonsoon (Ju (Junene-Novembe-Novemberr)) IIncidence ncidence rate rate 3.6-5.5/100.000/3.6-5.5/100.000/yearyear inin hyper- hyper-

endendeemimic c zonezone RRisiskk Fact Factoors :rs : FarmersFarmers DDMM Renal failureRenal failure Renal calculi Renal calculi Thalassémie/ Haemoglobin E or HThalassémie/ Haemoglobin E or H Steroid intakeSteroid intake, Alcoolism, Alcoolism

Risks factorsRisks factors MeanMean Age 42 yr. peak 40-60 yr.Age 42 yr. peak 40-60 yr. Season Variation : rainy seasonSeason Variation : rainy seasonRisk factorsRisk factors OR (95%CI)OR (95%CI)Preexisting renal diseasePreexisting renal disease 2.6 (1.5-5.6)2.6 (1.5-5.6)ThalassemiaThalassemia 11.8 (2.5-54.5) 11.8 (2.5-54.5)MalignancyMalignancy 0.4 (0.1-0.9)0.4 (0.1-0.9)DiabetesDiabetes 4.8 (3.0-7.7)4.8 (3.0-7.7)Soil & water exposure Soil & water exposure 1.8 (0.6-5.4)1.8 (0.6-5.4)DM + Soil & water exposureDM + Soil & water exposure 6.3 (3.8-10.6.3 (3.8-10.4)4) Exposure to soil and water in paddy Exposure to soil and water in paddy

fields fields

Suputtamongkol Y. Intern J Epidemio 1994;23:1082-90

Suputtamongkol Y.CID 1999;29:408-13

Epidemiology of Epidemiology of B. pseudomalleiB. pseudomallei in soil in soilin Thailandin Thailand

Melioidosis by regionMelioidosis by region

RegionRegion Infection Rate/ Infection Rate/ 100,000 in-100,000 in-

pateintspateints

NorthNorth 18 18

CentralCentral 13.4 13.4

NortheastNortheast 137.9137.9

SouthSouth 14.4 14.4

North 4.4%

Northeast20.4%

Central 6.1%

South5.9%

Vuddhakul V. Am J Med Hyg 1999;60:458-61.

PathogenesisPathogenesis Acute Infection :Acute Infection :

– Direct inoculation during workDirect inoculation during work– Inhalation Inhalation – DrowningDrowning

Reactivation : Reactivation : – Dormant intracellular after exposureDormant intracellular after exposure– Relapse by same ribotypeRelapse by same ribotype

NNaturatural hal historistoryy ofof M MeelioïdoslioïdosisisInoculation, InhalationIngestion

Séroconversion asymptomatiqueInfection locale

(aiguë ou chronique)

Latence

Dissémination

Sepsie fulminante

et mort

Résolution

CliniClinical featurescal features

CClinilinicalcal mmanifestations polymorphe anifestations polymorphe : : « the « the great mimicker »great mimicker »

CClinilinicalcal mmanifestation anifestation vary from chronic or vary from chronic or localilocalized infection to acute disseminated zed infection to acute disseminated infection (septicemia)infection (septicemia)

All All organeorganes can be infecteds can be infected : : lunglung, , liverliver, , spleenspleen, , jointsjoints, , soft soft tissus, tissus, bone, bone, parotid.parotid.

Type of infectionType of infection Disseminated Septicemic Melioidosis Disseminated Septicemic Melioidosis

(DSM)(DSM) Non disseminated Septicemic Melioidosis Non disseminated Septicemic Melioidosis

(NSM)(NSM) Localized Melioidosis (LM)Localized Melioidosis (LM) Subclinical Melioidosis (SM)Subclinical Melioidosis (SM)

Disseminated Septicemic MelioidosisDisseminated Septicemic Melioidosis Acute manifestation : Acute manifestation : rapidrapid cliniclinicalcal d deetteeriorationrioration

( Septic shock)and( Septic shock)and d deevelopment velopment of of mmeetastatitastatic c abscessesabscesses

Blood culture positiveBlood culture positive Multiple organ involvement (Multiple organ involvement (>>2 organs)2 organs)

– Lung : blood borne pneumoniaLung : blood borne pneumonia– Skin : pustulesSkin : pustules– Liver : multiple abscessesLiver : multiple abscesses– Spleen : multiple abscessesSpleen : multiple abscesses– KidneysKidneys

High mortality rate : High mortality rate : 100% 100% withoutwithout treatment treatment, , 40% 40% withwith treatment treatment

Non-Disseminated Septicemic Non-Disseminated Septicemic MelioidosisMelioidosis

Blood culture positiveBlood culture positive Single or no organ involvementSingle or no organ involvement

– LungLung– LiverLiver– SpleenSpleen– MusculoskeletalMusculoskeletal

Low mortality rateLow mortality rate

Localized melioidosisLocalized melioidosis

Chronic manifestationChronic manifestation Blood culture negativeBlood culture negative Single organ involvementSingle organ involvement

– Lung : Pneumonia, abscessLung : Pneumonia, abscess

– Liver : abscess (single or multiple)Liver : abscess (single or multiple)

– Spleen : abscess(single or multiple)Spleen : abscess(single or multiple)

– Musculo-skeletal : septic arthritis, osteomyelitis, Musculo-skeletal : septic arthritis, osteomyelitis, pustulespustules, , abscess, lymphangitis…abscess, lymphangitis…

Low mortality and relapse rateLow mortality and relapse rate

Subclinical MelioidosisSubclinical Melioidosis

Serology positiveSerology positive MMeelioidoslioidosisis-infection due -infection due toto asymptomatic asymptomatic

carrier carrier :: SSeeroconversion + / roconversion + / almost in almost in endendeemimicc zone.(Ex : 80% zone.(Ex : 80% children children <4 years <4 years inin Nor Northth-e-eaast st of of Thaïlande). Thaïlande). Long term Long term RisRiskk of of cliniclinical diseasecal disease ( (up to up to 30 30 yearyears)s)It is called It is called « Vietnam time Bomb » « Vietnam time Bomb » inin Vietnam : Vietnam : 3.5% 3.5% ofof am ameericanrican soldiers soldiers trops basedtrops based in in Vietnam Vietnam with with sseerologrologyy +. (treatment +. (treatment notnot n neecesscessaryary, , but but surveillance surveillance is is importantimportant and required) and required)..

LungLung Abc Abcessess due to due to B. pseudomalleiB. pseudomallei

Pulmonary MelioidosisPulmonary Melioidosis

Cliché 1 Cliché 2: 10 jrs after

Bilateral Alveolar and interstitial InfiltrationCavity with fluid of RUL

LungLung Abc Abcessess due todue to B. pseudomalleiB. pseudomallei

1er cliché 2eme cliché

Melioidosis : Melioidosis : Skin & soft tissueSkin & soft tissue AbscessesAbscesses

Melioidosis : Melioidosis : Skin & soft tissueSkin & soft tissue AbscessesAbscesses

Before treatment 2 weeks after treatment

Melioidosis in LaosMelioidosis in LaosResearch collaboration :Research collaboration :

Welcome Trust- Mahosot- Oxford Welcome Trust- Mahosot- Oxford University, UKUniversity, UK

97 cases in Vientiane hospitals(1999-2006)97 cases in Vientiane hospitals(1999-2006)(78 cases Mahosot, 16 cases Settha, (78 cases Mahosot, 16 cases Settha, 2 cases 103 Hosp., 1 case Mittaphab)2 cases 103 Hosp., 1 case Mittaphab)

• 47 septicaemic / disseminated melioidosis :47 septicaemic / disseminated melioidosis : death : 5 casesdeath : 5 cases

50 localised melioidosis :50 localised melioidosis : parotid : 20 cases (5 adults)parotid : 20 cases (5 adults) Joint/soft tissues : 14 cases Joint/soft tissues : 14 cases lung abscess : 1 caselung abscess : 1 case Lymphadenitis : 3 cases Lymphadenitis : 3 cases Others : 12 casesOthers : 12 cases

DiagnosisDiagnosis

Can not be made clinically, only microbiologically**Can not be made clinically, only microbiologically**

1. Gram stain – Gram neg., bipolar staining (safety pin) 1. Gram stain – Gram neg., bipolar staining (safety pin)

2. Culture on Ashdown media : gold standard (48-72 h) material : 2. Culture on Ashdown media : gold standard (48-72 h) material : pus, pus, throat swabthroat swab, blood culture, blood culture

- colony morphology & color- colony morphology & color- natural resistance to gentamicin & colistine- natural resistance to gentamicin & colistine

3. Direct ImmunoFluorescence (DIF) & latex agglutination test are 3. Direct ImmunoFluorescence (DIF) & latex agglutination test are rapid test for early diagnosis : IF has 73 & 99% sens. & spec.rapid test for early diagnosis : IF has 73 & 99% sens. & spec.

4. 4. Imaging: Imaging: search for search for ababsscceessss ((found infound in 15% 15% of patients He of patients Hemo +) : mo +) : Chest Chest X RayX Ray, , Ultrasound Ultrasound abdominalabdominal /prostate./prostate.

5. 5. SSeerologrologyy : not : not valu valuableable in in endendeemimic areasc areas..

** for this reason melioidosis is largely undiagnosed in ** for this reason melioidosis is largely undiagnosed in developing countries lacking lab facilitiesdeveloping countries lacking lab facilities

MorphologMorphologyy : : B.pseudomalleiB.pseudomallei inin culture culture Source : « The Lancet.vol 361.May 17,2003, Melioidosis, Prof NJ White »Source : « The Lancet.vol 361.May 17,2003, Melioidosis, Prof NJ White »

MMeelioidoslioidosisis : : bottles ofbottles of HeHemoculture moculture Characteristic Characteristic BBurkholderiaurkholderia

pseudomallei pseudomallei pelliclepellicle

QuantitQuantity of y of B.pseudomalleiB.pseudomallei(ARA-) (ARA-) andand B.ThailandB.Thailandensisensis (ARA+) (ARA+) byby r reegiongion

((By Mrs By Mrs V.Wuthiekanun, Wellcome Unit, FTM,Mahidol University, BKK)V.Wuthiekanun, Wellcome Unit, FTM,Mahidol University, BKK)

ARA-ARA- Median (range)Median (range)Colony forming unit/gColony forming unit/g

ARA+ARA+ Median (range)Median (range)Colony forming unit/gColony forming unit/g

NE ThailandNE Thailand 68%68% 500 (1-17.000)500 (1-17.000) 32%32% 30 (1-1.200)30 (1-1.200)

C. ThailandC. Thailand 0%0% -- 100%100% 10 (1-600)10 (1-600)

LaosLaos 68%68% 40 (1-1.200)40 (1-1.200) 32%32% 100(1-5.800)100(1-5.800)

Southern Southern VietnamVietnam

21%21% 30(1-2000)30(1-2000) 79%79% 400(1-18.000)400(1-18.000)

Melioidosis should be suspected in patients Melioidosis should be suspected in patients

1.1. With community-acquired With community-acquired sepsissepsis or or pneumoniapneumonia or or visceral abscessesvisceral abscesses or or parotid abscessparotid abscess

2.2. Living in / returning from endemic areas Living in / returning from endemic areas

3.3. Exposed to soil and water : Exposed to soil and water : rice farmersrice farmers

4.4. With co-morbidities = particular risk factors (n°1 risk factor With co-morbidities = particular risk factors (n°1 risk factor is diabetes)is diabetes)

5.5. With sepsis resistant to usual 1With sepsis resistant to usual 1st st line antibiotics :line antibiotics :penicillin, ceftriaxone, aminoglycosides, macrolides... penicillin, ceftriaxone, aminoglycosides, macrolides...

TrTreaeatmenttment Importance of case management : Importance of case management : ddeepend pend on early and on early and

accuracy of accuracy of diagnosidiagnosiss.. Thinking of Thinking of mmeelioïdoslioïdosis in patient with is in patient with communcommunity ity acqui acquirreedd

septicsepticeemimiaa in patients at riskin patients at risk SSepticepticeemimicc fformorm needs to be treated needs to be treated quickly quickly beforebefore

confirmation confirmation of diagnosisof diagnosis . . LLocaliseocalisedd fform orm need to be need to be confirmconfirmeded before treatment and all before treatment and all

abscesses need to be abscesses need to be draindraineded if if possible.possible. Treatment of Treatment of sseevveere form = re form = expensive expensive (424$US); (424$US); High High

MortalitMortalityy, , in spite of in spite of optimal treatment ~ 40%.optimal treatment ~ 40%. Treatment of lTreatment of localiseocalisedd form form less expensiveless expensive = 124 $US; = 124 $US; Low Low

mortalitmortalityy

MMeelioidoslioidosisis : Princip : Principlle e ofof tr treateatmentment

1.1. TTreatment reatment complexe , long, complexe , long, expensiveexpensive,, problprobleem m ofof compliance compliance» LLong Durong Duration ation : 5 – 6 mo: 5 – 6 monthsnths ! ! » 2 phases: 2 phases: Intensive thenIntensive then maintenancemaintenance » requirrequireded association association of lots of drugsof lots of drugs : 3 . : 3 .» High High doses doses and and IV initiale ( min. 10 days )IV initiale ( min. 10 days )» Expensive Expensive (Ceftazidime, Imipenem = env. 100 US$/(Ceftazidime, Imipenem = env. 100 US$/dd

2.2. Need to be started without Need to be started without ddelay elay ( (early early diagnosidiagnosiss))3.3. Late resLate response ponse toto treatment : moy 9 treatment : moy 9 dd n notot conclu concludde e too early for too early for

treatment failure.treatment failure.4.4. ReRelapselapse : : * taux * taux increasedincreased : 10% : 10% afterafter treatment adequat ; 20% treatment adequat ; 20%

if if treatment < 20 treatment < 20 weeks.weeks.* d* deelalayy moy. moy. of relapse of relapse = 21 = 21 weeks inweeks inThailandThailand

5.5. In childrenIn children : : less severe less severe treatment treatment more more simple simple and shorter and shorter (8 (8 weeksweeks) if has localised disease) if has localised disease

TrTreateatment : septicment : septiceaeamimic Melioidosisc Melioidosis(Mahosot Microbiology Review, n(Mahosot Microbiology Review, no 4, Feb 2006o 4, Feb 2006))

1.1. Intensive Intensive TTT :TTT : 10 – 14 days10 – 14 days Ceftaxidime :Ceftaxidime : IV dose 120 mg/kg/ IV dose 120 mg/kg/dayday 3 div.dose 3 div.dose lessless 10 d. 10 d.

Adult 50 Kg 2g IVD every 8 hours.Adult 50 Kg 2g IVD every 8 hours. Or Or Co-Amoxyclav (Augmentin)Co-Amoxyclav (Augmentin) IV dose 160mg/kg/j div 6 IV dose 160mg/kg/j div 6

Adult 50 Kg, 1,2g IVD every 4 hoursAdult 50 Kg, 1,2g IVD every 4 hours2 2 MaintenanceMaintenance TTT Per Os (conventionnTTT Per Os (conventionnaal TTT):l TTT):

- - DoxycyclineDoxycycline 4mg/kg/ 4mg/kg/dd in 1 single dosein 1 single dose : 12-: 12-20 20 weeksweeks..- - Cotrimoxazole Cotrimoxazole 10/50mg/kg/j 10/50mg/kg/j in 2 in 2 div 2 ddiv 2 dosesoses : : 12- 12-20 20 weeksweeks..

OOrr - - Co-Amoxyclav Co-Amoxyclav (Augmentin) 30/15mg/kg/j (Augmentin) 30/15mg/kg/j in 3 in 3 divdiv.. dosesdoses durdurationation = 20 = 20 weeksweeks..- Amoxycilline- Amoxycilline 30mg/kg/j 30mg/kg/j in 3 in 3 divdiv. doses. doses = 20 = 20 weeksweeks

TrTreaeatment : localitment : localised Melioidosissed Melioidosis (Mahosot Microbiology Review, n(Mahosot Microbiology Review, no 4, Feb 2006o 4, Feb 2006))

TTT TTT Per osPer os ( (CConventionnonventionnaal TTT): l TTT):

1.1. DoxycyclineDoxycycline 4mg/kg/ 4mg/kg/dd in 1 single dosein 1 single dose : 12-: 12-20 20 ww..2.2. Cotrimoxazole Cotrimoxazole 10/50mg/kg/10/50mg/kg/d in 2 d in 2 div 2 ddiv 2 dosesoses : : 12- 12-20 20 weeksweeks. .

( adult 50 Kg : 2 tablets 960 mg x 2/d)( adult 50 Kg : 2 tablets 960 mg x 2/d)OOrr

3.3. Co-Amoxyclav Co-Amoxyclav (Augmentin) 30/15mg/kg/(Augmentin) 30/15mg/kg/dd in 3 in 3 divdiv.. doses . doses . durdurationation = 20 = 20 weeksweeks..

4.4. AmoxycillineAmoxycilline 30mg/kg/ 30mg/kg/d in 3 d in 3 divdiv. doses. doses = 20 = 20 weeksweeks

Follow up and Follow up and pr preeventionvention

Follow up is Follow up is nneecessacessary once a month after ry once a month after hospital discharge hospital discharge ..

ProProtection of wounds during working in tection of wounds during working in paddy fieldspaddy fields . .

Wearing bootsWearing boots and gloves during working and gloves during working with soilwith soil..

No No vaccinvaccinee available.available.

Conclusion Conclusion ((11))

MMeelioidoslioidosisis : : eemergmerging diseaseing disease with tendency ofwith tendency of dissdisseemination, mination, withwith r reeservoir hydro-tellurique.servoir hydro-tellurique.

BBGNGN, a, aeerobirobicc, mobile, bipola, mobile, bipolar staining( safety pin)r staining( safety pin) One of causeOne of cause respons responsiible ble of of communcommunity acquiredity acquired

septicasepticaeemimia with higha with high mortalit mortality in SE y in SE AsiAsia and a and NorthNorth Australi Australiaa

RReesistant sistant to to empiriempiric treatmentc treatment of of communcommunity ity acquiredacquired septic septiceemimiaa..

Primary iPrimary infection nfection : : sseasonaleasonal inin monsoonmonsoon

Conclusion Conclusion ((22)) Transmission Transmission : inoculation : inoculation + + o+ + or inhalationr inhalation Very Very commcommoon n in in immunoimmunocompromised compromised : :

DDMM, , FarmersFarmers, Renal calculi, Renal failure , Renal calculi, Renal failure steroid intakesteroid intake, alcoholism, alcoholism

« Gr« Great clinical mimickereat clinical mimicker  »:  »: CClinilinicalcal diagnosi diagnosiss ddifficulifficultt except except ParotidParotid

abscessabscess unilat unilateeral ral in children in children .. SepticaSepticaeemimiaa = = alwaysalways H Heemoculture moculture and and

ThroatswabThroatswab

Conclusion Conclusion ((33)): :

TTreatmentreatment of of septicsepticemia expensiveemia expensive ~ ~ 424 $US424 $US TTreatmentreatment of of localilocalizedzed F.less expensiveF.less expensive ~ ~ 124 $US124 $US PProlongrolongeded treatment is treatment is nneecessarcessary for all casesy for all cases ( (in in

spite ofspite of TTT, F° persist 10 ~ TTT, F° persist 10 ~ daysdays)) High High MortalitMortality in spite of y in spite of optimal optimal treatmenttreatment 40%. 40%. High rHigh reelapselapse fr freequenquency 15%cy 15% andand latelate.. ImmunitImmunityy acqu acquired not ired not durable.durable. PrPreevention : vention : wearing wearing bobooots, ts, gloves during working gloves during working

with soilwith soil.. No No vaccinvaccinee available available ..

¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1 ­­£ö­À¥ñ®°øɧ¾¨­º¾¨÷­24­¯ó,­§¾¸­¾,­§ö­£ö­À¥ñ®°øɧ¾¨­º¾¨÷­24­¯ó,­§¾¸­¾,­§ö­§¾©­ì¾¸¦ø¤­À´õº¤¸ñ¤¸¼¤,­Á¢¸¤¸¼¤¥ñ­,­§¾©­ì¾¸¦ø¤­À´õº¤¸ñ¤¸¼¤,­Á¢¸¤¸¼¤¥ñ­,­ÁªÈ¤­¤¾­­Áìɸ,­´óìø¡­7­£ö­ÁªÈ¤­¤¾­­Áìɸ,­´óìø¡­7­£ö­

À¢í¾Â»¤Ïð¨Éº­́ 󺾡¾­Ä¢É¦ø¤­Áì½­À¢í¾Â»¤Ïð¨Éº­́ 󺾡¾­Ä¢É¦ø¤­Áì½­Á¡È¨¾¸>­1­À©õº­­­Ä¢É¦ø¤ªìº©­²Éº´¡ñ®Á¡È¨¾¸>­1­À©õº­­­Ä¢É¦ø¤ªìº©­²Éº´¡ñ®´óº¾¡¾­À¥ñ®­¹ö¸Á»¤­Á콭ĺ§¿À»œº­´óº¾¡¾­À¥ñ®­¹ö¸Á»¤­Á콭ĺ§¿À»œº­Á¡È¨¾¸>­1­À©õº­­.Á¡È¨¾¸>­1­À©õº­­.

À£ó¨À¢í¾­º­Â»¤ÏðÀ´õº¤¸ñ¤¸¼¤­Áì½­­¯†­À£ó¨À¢í¾­º­Â»¤ÏðÀ´õº¤¸ñ¤¸¼¤­Áì½­­¯†­¯ö¸­©É¸¨­¯ö¸­©É¸¨­Ampicilline IV dose 3 g/ Ampicilline IV dose 3 g/ ´œ´œ 3­­Áì½­3­­Áì½­­kanamycine­6­´œ­,­ÁªÈº¾¡¾­®Ò©ó¢œ­.­­kanamycine­6­´œ­,­ÁªÈº¾¡¾­®Ò©ó¢œ­.­

­¿¦‰¤²½Á­¡§õ´À§œºÂ»¤Ïð´½Â¹¦ö©.­¿¦‰¤²½Á­¡§õ´À§œºÂ»¤Ïð´½Â¹¦ö©.

¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1 ìñ¡¦½­½¢º¤Ä¢Ê­:­£Èº¨ÅÀ²š´¢œ­­Áì½­Äìñ¡¦½­½¢º¤Ä¢Ê­:­£Èº¨ÅÀ²š´¢œ­­Á콭Ģɦø¤ªìº©¢É¦ø¤ªìº©

º¾¡¾­¦ö´êö®­:­À¥ñ®­¹ö¸Á»¤,­®Òº¾¡¾­¦ö´êö®­:­À¥ñ®­¹ö¸Á»¤,­®Ò´óξ¸¦„­,­ºÈº­­À²ñ¨,­¯¸©¡É¾´§š­,­¯¸©»¾¡´óξ¸¦„­,­ºÈº­­À²ñ¨,­¯¸©¡É¾´§š­,­¯¸©»¾¡

ĺ§¿À»œº­Á¡È¨¾¸>­1­À©õº­­,­Äº§¿À»œº­Á¡È¨¾¸>­1­À©õº­­,­ê¿ºò©ÄºÁ¹É¤,­ªÒ´¾Äº´ó¢š¡½Àꆦó꿺ò©ÄºÁ¹É¤,­ªÒ´¾Äº´ó¢š¡½Àꆦ󢾸®Ò´óÀìõº©¯ö­,­¢š¡½ÀꆭÀ¯ñ­­¢¾¸®Ò´óÀìõº©¯ö­,­¢š¡½ÀꆭÀ¯ñ­­Õκ¤À¸ì¾À¢í¾­º­Â»¤ÏðÕκ¤À¸ì¾À¢í¾­º­Â»¤Ïð

´óº¾¡¾­À¥ñ®Àºò¡ìȾ´Ä¯ê¾¤¹ìñ¤´óº¾¡¾­À¥ñ®Àºò¡ìȾ´Ä¯ê¾¤¹ìñ¤

¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1­:­¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1­:­¯½¹¸ñ©¯½¹¸ñ©

1.1. ­­¯½¹¸ñ©¦È¸­ªö¸­:¯½¹¸ñ©¦È¸­ªö¸­:­­-Œ­­­º÷®ñ©À¹©«õ¡ìø¡Â®´­1976­:­ªñ©-Œ­­­º÷®ñ©À¹©«õ¡ìø¡Â®´­1976­:­ªñ©

¢¾À®œº¤¢¸¾­Áì½­®¾¤£˜¤¡ð´óº¾¡¾­¢¾À®œº¤¢¸¾­Áì½­®¾¤£˜¤¡ð´óº¾¡¾­À¥ñ®µøÈ®ðìòÀ¸­¢¾ê†«õ¡ªñ©­Áì½­´ó­À¥ñ®µøÈ®ðìòÀ¸­¢¾ê†«õ¡ªñ©­Áì½­´ó­ÕĦÅĹ캺¡´¾..ÕĦÅĹ캺¡´¾..

Œ­­­Ä¢É­Malaria.Œ­­­Ä¢É­Malaria.Œ­­­®Ò´ó¯½¹¸ñ©Á²Éµ¾,­¦ø®µ¾­Áì½­¡ó­Œ­­­®Ò´ó¯½¹¸ñ©Á²Éµ¾,­¦ø®µ¾­Áì½­¡ó­

À¹ìí¾®¾¤À¸ì¾À¹ìí¾®¾¤À¸ì¾Œ­­­®Ò´ó­¯½¹¸ñ©­:­DM,­HTA,­HepatiteŒ­­­®Ò´ó­¯½¹¸ñ©­:­DM,­HTA,­Hepatite

2.2. ­¯½¹¸ñ©£º®£ö¸­:­­¯½¹¸ñ©£º®£ö¸­:­Œ­­Œ­­®Ò´ó­¯½¹¸ñ©:­DM,­HTA,­Hepatite,­´½À»ñ¤.®Ò´ó­¯½¹¸ñ©:­DM,­HTA,­Hepatite,­´½À»ñ¤.

¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1:­¡¾­¡ðì½­ó­£ö­À¥ñ®°øÉꆭ1:­¡¾­¡¸©¡¾¡¸©¡¾

TA : 130/70 mmHg , FC : 120/mn, T : 39.5 c, RR : TA : 130/70 mmHg , FC : 120/mn, T : 39.5 c, RR : 32/mn , Poids : 58 Kg.32/mn , Poids : 58 Kg.

¦½ªò©ó,­¦½²¾®ì¸´ºÈº­À²ñ¨,­¥õ©´É¾­,­¡ó­À¦½ªò©ó,­¦½²¾®ì¸´ºÈº­À²ñ¨,­¥õ©´É¾­,­¡ó­À¢í¾­®ÒÁ§®¨È¼¸­Áì½­º¾¥ö´­¯ö¡ªò¢í¾­®ÒÁ§®¨È¼¸­Áì½­º¾¥ö´­¯ö¡ªò

­­®Ò´óªÈº´¡½©ñ­,­®¸´¢¾­Áì½­rash.­®Ò´ó­®Ò´óªÈº´¡½©ñ­,­®¸´¢¾­Áì½­rash.­®Ò´ó­º¾¡¾­­Àìõº©Ä¹ìÁì½­Escarre­º¾¡¾­­Àìõº©Ä¹ìÁì½­Escarre­

Toux productive, dyspnee, tirage Toux productive, dyspnee, tirage ±, Dl thoracique.±, Dl thoracique. êɺ¤ºÈº­©ó,­ªñ®­Áì½­¯É¾¤£¿®Ò²ö®­.êɺ¤ºÈº­©ó,­ªñ®­Áì½­¯É¾¤£¿®Ò²ö®­. pas­de­signes­meninge­pas­de­signes­meninge­ Coeur : normal; Poumon : rales crepitants sommet PG.Coeur : normal; Poumon : rales crepitants sommet PG.

£¿«¾´£¿«¾´

ùɲ¸¡êȾ­¦½ÀÎ󴽪ò²½¨¾©Ã¹É²¸¡êȾ­¦½ÀÎ󴽪ò²½¨¾©¢º¤£ö­À¥ñ®©„¤¡È¾¸¢º¤£ö­À¥ñ®©„¤¡È¾¸´¾µÈ¾¤Îɺ¨­3­²½¨¾©?­²Éº´¦À­ó´¾µÈ¾¤Îɺ¨­3­²½¨¾©?­²Éº´¦À­ó¢Ó­´ø­ºÉ¾¤ºó¤¢º¤êȾ­¢Ó­´ø­ºÉ¾¤ºó¤¢º¤êȾ­

­­Á콭ùɲ¸¡êȾ­¦½ÀÎó¡¾­¡¸©¸ò­Á콭ùɲ¸¡êȾ­¦½ÀÎó¡¾­¡¸©¸ò­À£¾½­ê†¥¿À¯ñ­¦¿ìñ®¡¾­À£¾½­ê†¥¿À¯ñ­¦¿ìñ®¡¾­´½ªò²½¨¾©­¢º¤êȾ­?´½ªò²½¨¾©­¢º¤êȾ­?

£¿ªº®£¿ªº® (1) (1)

1.1. Tuberculose Tuberculose : F°: F° prolongée prolongée, , toux chronique avec toux chronique avec expectoration purulente, dyspnée, dl thoracique et Rales expectoration purulente, dyspnée, dl thoracique et Rales crépitants.crépitants.

2.2. Abcès du Abcès du poumon poumon à germes pyogéniquesà germes pyogéniques : : F°élevée, F°élevée, toux productive toux productive avec expectoration purulente, dyspnée, avec expectoration purulente, dyspnée, dl thoracique, Rales crépitants.dl thoracique, Rales crépitants.

3.3. Ostéite chroniqueOstéite chronique : F°élevée: F°élevée et prolongée et prolongée, , écoulement écoulement séreuse de la jambe amputée.séreuse de la jambe amputée.

4.4. Mélioidose pulmonaireMélioidose pulmonaire : : F°élevée, F°élevée, toux productive toux productive avec expectoration purulente, dyspnée, dl thoracique, avec expectoration purulente, dyspnée, dl thoracique, Rales crépitants.Rales crépitants. Cultivateur Cultivateur habitée dans une zone endémiquehabitée dans une zone endémique

£¿ªº®­£¿ªº®­(3)(3)

44.. Examens paracliniques à pratiquer :Examens paracliniques à pratiquer :- - NFS, HNFS, Hzz, groupage, groupage- Examen direct des crachats : BK et douves et - Examen direct des crachats : BK et douves et culture.culture.- Hémoculture et prélèvement de gorge pour - Hémoculture et prélèvement de gorge pour chercher chercher B.pseudomallei.B.pseudomallei.- Rx thorax : - Rx thorax : - Glycémie, Créatinine, - Glycémie, Créatinine, Azotémie, Ionogramme, Azotémie, Ionogramme, Bilan hépatique.Bilan hépatique.-- Rx de la jambe D (Tibia et péroné). Rx de la jambe D (Tibia et péroné).

£¿ªº®­£¿ªº®­(4) : (4) : RésultatsRésultats• NFS NFS à l’admission à l’admission :: Hte: 3 Hte: 366% ; Hb: % ; Hb: 1111g/l ; GB: g/l ; GB:

1212..0000/mm3, PN : 00/mm3, PN : 8686%, Lympho: %, Lympho: 14 14 %, Mono: %, Mono: 2,4%; Plaquettes : 2,4%; Plaquettes : 23230.000/mm3;0.000/mm3;HzHz : négatif : négatif ..

• NFS, VS:NFS, VS: Hte: 3Hte: 322% ; Hb: % ; Hb: 1111g/l ;g/l ;GR: GR: 3.335.000/mm3.335.000/mm3 3 ; ; GB: GB: 1717..3300/mm3, PN : 00/mm3, PN : 8888%, %, Lympho: Lympho: 8.4 8.4 %, Mono: %, Mono: 3.6 %. MCV: 96; 3.6 %. MCV: 96; Plaquettes : Plaquettes : 299.000299.000/mm3/mm3 ;;HzHz : négatif : négatif ..

• VS : 127 et 134 mm/hVS : 127 et 134 mm/h• Glycémie :Glycémie : 110055 mg/dl ; mg/dl ; Créatininémie :Créatininémie : 1 16565UM/l;UM/l;• Bilan hépatique : Bilan hépatique : Bil T : 0.75 et Bil D: 0.30 ; Bil T : 0.75 et Bil D: 0.30 ;

SGOT:SGOT:4040 UI/l; SGPT: UI/l; SGPT: 5050 UI/l; P.alcaline : UI/l; P.alcaline : 540540UI/l UI/l

£¿ªº®­£¿ªº®­(5) : (5) : RésultatsRésultats Ionogramme : Na :141, K : 3.05; Chlore : 102Ionogramme : Na :141, K : 3.05; Chlore : 102 Bicarbonate : 21.8 mmol/lBicarbonate : 21.8 mmol/l Hémoculture : negativeHémoculture : negative ED crachats : BK et Douves (-)ED crachats : BK et Douves (-) Culture des crachats : Culture des crachats : Proteus spProteus sp. (+). (+) Rx thorax : Abcès du poumon droitRx thorax : Abcès du poumon droit Prélèvement de la gorge : Prélèvement de la gorge : B.pseudomalleiB.pseudomallei (+) (+)

Examen bactériologiqueExamen bactériologique

Prélèvement de gorgePrélèvement de gorge sur le milieu de SBCTsur le milieu de SBCT: :

Aspect de pellicule Aspect de pellicule blanche à la surfaceblanche à la surface

positifpositif à à Burkholderia Burkholderia pseudomalleipseudomallei

Aspects radiologiquesAspects radiologiques

1er cliché 2eme cliché

Réponses Réponses Diagnostic positif : Diagnostic positif : - Abcès du Abcès du poumon poumon à à B.pseudomalleiB.pseudomallei . .

Traitement :Traitement :- Ceftazidime 120 mg/kg/j div.3 pendant 14 jsCeftazidime 120 mg/kg/j div.3 pendant 14 js adapté à adapté à

la Creatininémie.la Creatininémie.- TTT symptomatiqueTTT symptomatique- Re-équilibre hydro-électrolytiqueRe-équilibre hydro-électrolytique

Conseils au patient :Conseils au patient :

- Suivi régulier le traitement après la sortie pour - Suivi régulier le traitement après la sortie pour prévenir la rechute et immunité acquise pas durableprévenir la rechute et immunité acquise pas durable

ReferencesReferences

Chaowagul,W et al 1989: Melioidosis : a major cause of Community-acquired Chaowagul,W et al 1989: Melioidosis : a major cause of Community-acquired septicemia in Northeastern Thailand. J.Infect.Dis.159, 890-898.septicemia in Northeastern Thailand. J.Infect.Dis.159, 890-898.

N J White : Melioidosis .The Lancet 2003 ; Vol 361: May 17, 2003; 1715-22.N J White : Melioidosis .The Lancet 2003 ; Vol 361: May 17, 2003; 1715-22. Wuthiekanun, V, et al 1996 : Biochemical characteristics of clinical and Wuthiekanun, V, et al 1996 : Biochemical characteristics of clinical and

environnmental isolates of B.pseudomallei. J.Med.Microbiol.1996; 45: 408-412.environnmental isolates of B.pseudomallei. J.Med.Microbiol.1996; 45: 408-412. Phetsouvanh R. et al.: Melioidosis and Pandora’s box in the Lao People’s Phetsouvanh R. et al.: Melioidosis and Pandora’s box in the Lao People’s

Democratic Republic. Democratic Republic. Brief reports:Brief reports: Clinical Infectious DiseaseClinical Infectious Disease 2001;32: 653- 2001;32: 653-654.654.

Wuthiekanun, V.et al : Detection of Wuthiekanun, V.et al : Detection of Burkholderia pseudomalleiBurkholderia pseudomallei in soil within in soil within the Lao PDR . Journal of Clinical the Lao PDR . Journal of Clinical MicrobiolMicrobiology, Feb.2005, vol.43, nogy, Feb.2005, vol.43, n°2 : 923-°2 : 923-924924

Wirongrong Chierakul et al : Two randomized controlled trials of Ceftazidime Wirongrong Chierakul et al : Two randomized controlled trials of Ceftazidime alone vs Ceftazidime in combination with TMP-SMX for the treatment of alone vs Ceftazidime in combination with TMP-SMX for the treatment of severe Melioidosis. severe Melioidosis. Clinical Infectious DiseaseClinical Infectious Disease 200 20055;;4141: : 11051105--11131113..