Nghiên cứu đặc điểm dịch tễ học, lâm sàng bệnh tả và đề xuất các giải pháp phòng chống dịch ở việt nam

Phan Thj Nga To chirc cong tdc Vien Ve sinh dich te TtT Benh vien Benh truyen nhi€m Trung iroTig Vien Ve sinh djch te TIT Vien Ve sinh djch t l TIT Vien Ve sinh djch te T l / Vien Ve s

2010

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" TAI D 6 C L.4P C ^ NHA NUOC

g ^ i'\ i~^ A r% 'Ti'\^ri

Wtr f>5:J A KHO.A HOC C O N G NGM& fWS XAl

:;s» «BSB fM tri d l {*i: Vi6n Vf sinh dich tl Tniag ««ng

M mm M m J PGS TS !%By& Trla Hi&i

HIN6i-2010

BO KHOA HOC VA CONG NGHE B O Y TE

DE TAI DOC LAP CAP NHA NUCC

BAO CAO TONG HOP

KET QUA KHOA HQC CONG NGHE DE TAI

NGHIEN CLTU DAC DIEM DICH TE HOC,

LAM S A N G BENH T A V A DE X U A T CAC GIAI P H A P

PHONG CHONG DICH d VIET NAM

MA SO: DTDL 2008 G/21

Chii nhiem de tai

PGS TS Nguyen Tran Hien PGS TSTTfang ©irc Anh

Ban chu nhiem chuong trinh Bp Khoa hpc va Cong nghe

Ha Noi-2010

(Danh sdch nhiing cd nhdn da ddng gop sang tao chit yen cho de tdi, du an

dugc sap xep theo thir ttr dd thoa thuan)

1 Fen de tai, du an: "Nghien ciiu dac diem dich te hpc, lam sang benh ta va de xuat cac giai phap phong chong dich tai Viet Nam"

Mas6; 0TDL.2OO8 G/21

Thuoc: - De tai doc lap cap nha nuoc ITnh vuc Y duoc

2 Thoi gian thuc hien : 01/2008- 3/2010

3 T6 chiic chii tri: Bp Y te

4 Co quan chu quan: Vien Ve sinh Djch te Trung ucmg

5 Tac gia thuc hien de tai tren gom nhiing ngucri co ten trong danh sach sau (khong qud 10 ngudi):

PGS TS Nguyen Tran Hien

TS Nguyen Van Kinh

TS Tran Nhu- Du-ong

PGS TS Nguyen Binh Minh

Ths Ngo Tuan CuoTig

Ths Tran Huy Hoang

Ths Le Thanh Huong

BS Nguyen Quang Minh

PGS TS Nguyen Thu Yen

PGS TS Phan Thj Nga

To chirc cong tdc

Vien Ve sinh dich te TtT Benh vien Benh truyen nhi€m Trung iroTig Vien Ve sinh djch te TIT Vien Ve sinh djch t l TIT Vien Ve sinh djch te T l / Vien Ve sinh djch te TIT Vien Ve sinh djch te TlT Vien Ve sinh djch te TIT

Chti nhiem de tai

PGS TS Nguyin Tran Hien

.URUNG L PGSrTSflBang Dire Anh

VIEN VE SINH DICH TE TRUNG T/ONG Doc lap - Tu- do - Hanh phiic

//ti jVpf ngay thdng nam 2010

DANH SACH CAC TAG GIA THAM GIA THl/C HI^N

DK TAI KHCN CAP NHA NlTdC

1 Ten d6 tai, du an: "Nghi6n ciiu d^c diem dich te hpc lam s^ng benh ta v^ de xuat cac giai phap phong ch6ng djch t?i Vi$t Nam"

Masa: 0TDL.2OO8G/21

Thupc: D^ tai dpc lap cap nha nuac ITnh virc Y duac

2 Thai gian thirc hien : 01/2008- 3/2010

3 76 chitc chil ffi: Bp Y ti

4 Co quan chu quan: ViSn Ve sinh Dich te Trung uong

5 Tac gia tham gia thyc hien dl tai tren g6m nhiing nguoi co ten trong danh sach sau:

BS Ngu Duy Nghia

Bs Pham Dire Tho

Ths BS Pham Quang Thai

BS Nguyen Hihi TSm

TS Hoang Van Tan

CN Nguyin Hoai Thu

CN Le Huy Hoang

Ths BS Ha Dinh

Ngu-Td chuc cong tdc

Vien Ve sinh dich te Trung uoTig

Vien Ve sinh djch t€ Trung utfng

Vien V | sinh djch te Trung uong

Vien Ve sinh djch tl Trung utmg

Vien Ve sinh djch te Trung uong

Vien Ve sinh djch te Trung uong

Vien Ve sinh djch te Trung uong

Vien Ve sinh djch te Trung uong

Vien Ve sinh djch te Trung uong

Vien Ve sinh djch te Trung uong

Vien Vf sinh dich te Trung uong

Trung tam Y te du phong tinh Thanh Hoa

Ths BS Nguyen Trung Cap

Ths Nguyen Tien Lam

PGS TS Nguyen Vii Trung

Ths Dao Tuyet Trinh

Ths BS T? Thi Dieu Ngan

BS CKII Nguyen Minh Ha

BS CKI Doan Van Trung

Ths BS Tr4n Thi Phu-ong

Thuy

BS Tran Thj Hai Ninh

Ths BS Trin Van Giang

BS Nguyen Thj Bich Dao

BS CKIL Ng Thi Dire Hien

Trung tam V te dy phong tinh Ha Tinh

Trung tam V te dy phong TP Ha Noi

Trung tam Y te dy phong TP Hii Nyi

Trung tam Y te dy phong TP HSi Phong

Trung tam Y te dy phong TP Hii Phdng

Trung tam Y te dy phong tinh Nam Djnh

Trung tSm Y te dy phong ti'nh Nam Djnh

Benh vien Benh Nhi^t Ddi Trung uong

Benh viin Benh Nhift Ddi Trung vong

Bfnh vifn Bfnh Nhift Ddi Trung uong

Bf nh vifn Benh Nhift Ddi Trung uomg

Benh vien Benh Nhiet Ddi Trung uong

Benh vien Bfnh Nhift Ddi Trung uong

Bf nh vifn Bfnh Nhift Ddi Trung inmg

Benh vien Benh Nhift Ddi Trung uong ^j;:

Bfnh vifn Bfnh Nhiet Ddi Trung uong

Benh vifn Bfnh Nhift Ddi Trung uong

Bfnh vifn Benh Nhift Ddi Trung uomg

Bfnh vien Bfnh Nhiet Ddi Trung irong

Benh vifn Bfnh Nhift Ddi Trung uwng

Bfnh vifn Bfnh Nhiet Ddi Trung inmg

Bfnh vien Da Ichoa Dong Da, Ha Ngi

Bfnh vien Da khoa Sain Paul, Ha Noi

BS Nguyen Quang Tuan

BS Nguyen Hanh Chung

BS Biii Due Long

BS Le Trung Dung

BS Nguyen Hoai Nam

BS Trkn Van Lugng

BS LS Qui

BS Nguyin XuSn Hoa

Benh vien Da khoa Ha Ddng, Ha Noi Benh vien Da khoa Bo Nong Nghiep, Ha Nfi

Benh viSn Bach Mai, Ha Noi Benh vien Da khoa tinh BSc Ninh Bfnh vien Da khoa tinh Hai Duong Benh vien Da khoa Viet Tiep, Hai Phong Benh vien Da khoa Quynh Luu, Nghe An Bfnh vien Da khoa tinh Thanh Hoa Benh vien Da khoa tinh Ha TTnh Benh vien Da khoa tinh Nam Djnh

Chii nhiem de tai

PGS TS Nguyin TrSn Hien

PGS TS Dang Due Anh

Muc luc

DANH MVC CAC Ki Hl£U, CHU^ V I £ T T A T 6

DANH MVC CAC BANG 12

DANH MVC CAC HINH 18

DANH MVC CAC BifeU D 6 22

MdDAU 25 CHirONG 1 TONG QUAN 29

1.1 Tinh hinh nghien curu ngoai nirac lien quan den de tai 29

1.2 Tinh hinh nghien cihi trong nuac lien quan d^n dh tai 32

1.3 Dac diem sinh hpc ciia vi khuan td 34

1.3.1 DSc diem vi sinh vSt hpc 34

1.3.2 Chan doan vi khuSnta 37

1.4 Dac di6m dich t l hpc bSnh ta 38

1.4.1 Nguon truyen nhilm 38

1.4.2 Phucfng thiic liy truySn 39

1.4.3 Tinh cam nhiem 42

1.4.4 Cac yeu to nguy ca cua benh ta 43

1.5 Mpt so yeu to canh bao dich 44

1.6 Dac dilm lam sang cua benh ta 45

1.6.1 Tri$u chung cua b$nh ta 45

1.6.2 Chandoan 46

1.6.3 Dilu tri 46 1.7 Xiily 6 dich va dy phong benh ta 47

CHU^OfNG 2 VAT U ? U VA PHl/ONG PHAP NGHIEN ClTU 48

2.1 Dac diem dich te hoc va lam sang cua benh ta 48

2.1.1 Dac diem dich te hoc 48

2.1.1.1 Nghiin cuu mo td dgc diim djch te hoc cua vu dich 48

2.1.1.2 Xdy dung bdn do dich te binh td tgi Hd Noi bdng ung dung hy thu^t

he thdng dinh vi dia ly 57

2.1.1.3 Xdc dinh cdc yiu to nguy ca 52

2.1.1.4 Xdc dinh tyle ngudi lanh mang vi khudn td a mot so vung co dich 63

2.1.1.5 Nghien cuu xdc dinh su luu hdnh cua vi khudn td/E.coli o moi

trudng nu&c, thuc phdm va d0ng vdt thuy sinh a cdc viing co dich 65

2.1.1.6 Nghien cuu xdc dinh s\e thich ung cua vi khudn td trong mdm torn

thuong phdm 76

vd kha nang sinh dgc Id theo dia du vd thai gian 79

2.1.2 Dac diem Idm sdng cua b^nh td

2.2 D5c diem djch t l hpc phan tii ciia bfnh td vd dp dyng trong dy bdo djch 90

2.2.1 DJc dilm djch te hpc phan til

2.2.2 Cdc chi so cdnh bdo djch td '"^ 2.3 Nghign cihi hodn thien quy trinh chin dodn vd di^u trj bfnh td 113

2.4 Nghign ciiu hodn thifn quy trinh xii \j 6 djch vd dy ph6ng bfnh ti 115

2.5 Dao ditc nghien ciiu ' "

CHirONG 3 K t T QUA ' ' ^

3.1 D?c di^m djch tl hpc vd lam sdng bfnh td 1 ' 7

3.1.1 DJc dilm djch tl hpc " ^

3.1.1.1 Dac diim dich ti hgc ciia dich lit nim 2007-2009 IH

3.1.1.2 Xdy dung bdn id djch ti benh ta lai Hd N0i bing mg dvng kp thudt

hfthSng dinh vi dia ly (GPS) HI

3 1.1.3 Xdc dinh Ciic yiu l6 nguy ca ciia b^nh td 136

3.1.1.4 Xdc dinh ty le ngudi lanh mang vi khudn tadm0l s6 vitng c6 dich 166

3.1.1.5 Xdc dinh syt luu hanh cita vi khudn td/E.coli d mdi trudng nude,

ihijtcphdm vd dong vat Ibuy sinh a cac vimg cd dich 169

3.1.1.6 Nghien ciru xdc dinh su thich ling cua vi khuin Id trong mdt s6

logi mdu thicc phdm 175 3.1.1.7 Xdc dinh muc dq khdng thuoc khdng sinh cua cdc chung vi khudn td

vd khd nang sinh doc id theo dia duvd thdi gian 178

3.1.2 Mo td ddc dilm lam sdng bfnh td a miln Bdc Vift Nam 2009 185

3.1.2.1 Bgcdiemchung cim benh nhdn vd mat so yeu to nguy ca lien quan

den khd ndng nhiem td 185 3.1.2.2 Bac diim ldm sdng cua cdc benh nhdn mdc bfnh Id 190

3.1.2.3 Dien bien cdc trieu chirng: 193

3.2 Ddc diem dich t l hpc phdn tii va dp dyng trong dy bdo djch 197

3.2.1 D|c dilm dich te hpc phdn hi 197

3.2.1.1 Chiing vi khudn 797 3.2.1.2 Bdc tinh kliu Mnh ;p7 3.2.1.3 D^c tinh kiiu gen jgg 3.2.1.4 MSi lien quan dich te hoc giiia cdc chung 203

3.2.2 Cdc chi s6 cdnh bdo djch 212

3.2.2.1 Phdthi^n V.cholerae 01, 0139 va NAG trong moi trudng nuac 212

3.2.2.2 Kit qud phdn lap vibriophage va xdc dinh Ogc diim hinh dang cia

vibriophage 2I6 3.2.2.3 Hinh dgng vibriophage quan sdt dudi kinh hiin vi diln tic 217

3.2.2.4 Kit qud phat hiinfllamentousvd kappa phage 220

3.2.2.5 Bi xudt chi s6 dv bdo 222

3.3.1 Danh gia ve viec bu dich duong uong trong vu dich ta 2007 - 2009 tai

mi§n Bac Viet Nam 223 3.3.2 Danh gia vl dich truyen doi voi benh nhan ta 227

3.3.3 Kit qua khang sinh do va danh gia ve sil dung khang sinh 231

3.3.4 Danh gia vl tho'i gian tieu chay, thai gian nam vien va thai gian con

vi khuan trong phSn 237 3.3.5 Danh gid vl anh hudng cua thuoc chong tieu chay 243

3.3.6 Danh gia vl cd bi$n phap hoi sure benh nhan nSng 247

3.4 Hoan thien quy trinh xu ly va du phong benh t& 249

3.4.1 Dinh nghTa, phat hien ca benli 249

3.4.2 Xir lyo dich 250

3.4.2 1 Doi vai benh nhdn 250 3.4.2.2 Tieu chudn cho binh nhdn ra viin 251

3.4.2.3 Xulyphdn vd chdt thdi cua binh nhdn 251

3.4.2.4 Xu ly moi truong xung quanh 253

3.4.2.5 Xuly nguon nuac 254 3.4.2.6 Doi v&i nguai tiep xuc 254

3.4.2.7 Kit thuc 6 dich td 255 3.4.2.8 Phong chong dich 256 3.4.2.9 Kho khdn vd tdn tgi 256

CHU'ONG 4 BAN LUAN 258 4.1 Dac dilm dich te hpc va lam sang ciia benh ta 258

4.1.1 Dac diem dich te hoc cua benh ta 258

4.1.1.1 Dgc di&m dich ti hoc cita dich td ndm 2007 - 2009 258

4.1.1.2 Phdn bo benh nhdn theo giai 262

4.1.1.3 Phdn bo benh nhdn theo nhom tuoi 262

4.1.1.4 Phdn bo benh nhdn theo nghe nghiep 263

4.1.1.5 Xdy dung bdn do dich te benh td lgi Hd Noi bang ung dung ky thudt

hi thdng dinh vi dia ly (GPS) 264

4.1.1.6 Xdc dinh cdcyeu td nguy ca ciia binh td 265

4.1.1.7 Xdc dinh tyle nguai lanh mang vi khudn td dmot sd vungco dich 276

4.1.1.8 Xdc dinh su luu hdnh cua vi khudn td/E coli a moi truong nuac,

thucphdm vd ddng vat thuy sinh d cdc viingco dich 278

4.1.1.9 Xdc dinh muc do khdng thuoc khdng sinh cua cdc chung vi khudn td

vd khd ndng sinh dpc td theo dia duvd thcri gian 283

A.X.I Dac diem lam sang cua b$nh ta 286

4.1.2.1 Phdn bd cdc ca benh nhgp viin theo diadu 286

4.1.2.2 Phdn bo benh nhdn trong thai gian co dich 286

4.1.2.3 Dgc diim ldm sdng binh nhdn mdc td 287

4.1.3 Dgc dilm can lam sang benh ta 290

4.1.3.1 Vihuyithoc 290

4.2 Ddc diem djch t l hpc phan tir vd dp dyng trong dy bdo djch 292

4.2.1 Ddc di6m djch tl hpc phan til ^ ' ^

4.2.2 Cdc chi s6 canh bdo djch 2 ' *

4.2.3 Hodn thifn quy trinh chan dodn vd di^u trj bfnh td 302

4.2.3.1 Lieu phdp bil dich duang uong ^"^

4.2.3.2 Lieu phdp iruyin dich • •'''•'

4.2.3.3 vi so luQmg dich Iruyin trong 5 ngdy ddu •'"(J

4.2.3.4 Anh hucmg cua truyin djch din Natri vd Kali mdu 307

4.2.3.5 Vdn di sti difng khdng sinh va do nhay cdm cua vi khudn la vdi

khdng sinh ^08

4 2.3.6 vi thai gian tieu chdy, thai gian ndm vien, thai gian cdn vi khudn

Irong phdn HO 4.2.3.7 Anh huang cua cdc thudc chdng tiSu chdy 312

4.2.3.8 Bdnh gid cdc bien phdp hoi siic bfnh nhdn ndng 313

4.3 Hodn thifn quy trinh xii ly vd dy ph6ng bfnh td 314

CHU'ONG 5 K^TLUAN 316

5.1 DJc di^m djch t i hpc vd lam sdng bfnh td 316

5.1.1 Dich tl hpc bfnh td ndm 2007 - 2009 tjii mien Bdc 316

5.1.1.1 Ddc diem dich te hoc ciia vu dich 316

5.1.1.2 Cdcyeu to nguy co vd nguon gdc vii dich 316

5.1.1.3 Ty le nguai idnh mang vi khudn td trong vu dich, 2007-2009 3J7

5.1.1.4 Sv luu hdnh ciia V.cholerae/E.coli a mdi trudng nuoc, thucphdmvd

cdc dpng vdl thtiy sinh tai cdc viing co dich 317

5.1.1.5 Mac da khdng thudc Ididng sinh vd khd ndng sinh d0c tS cua

cdc chiing vi khudn Id theo dia duvd thai gian 317

5.1.2 Dac diem lam sang benh td 318 5.2 Ddc dilm dich tl hgc phdn tii vd dp dyng trong dy bdo djch 318

5.2.1 Ddc di^m chiing vi khuk td Vift Nam gdy djch 318

5.2.2 Cac chi so cdnh bdo djch td 318 5.3 Hoan thifn quy trinh chan dodn va dilu trj bfnh td 318

5.3.1 Hodn thifn quy trinh chan dodn bfnh td 318

5.3.2 Hodn thifn quy trinh dilu hi bfnh td 318

5.3.3 Hodn thifn quy trinh xii 1^ 6 djch vd dy phdng bfnh td 319

5.3.4 Xdy dyng quy trinh sdn xuat khdng huylt thanh td djc hifu 6 qui mo

phdng thi nghif m 319

5.4 Xay dyng quy trinh sdn xudt bp sinh pham chan dodn nhanh vi khuan ta a

qui mo phong thi nghif m 319

5.5 Xay dyng tieu chuan co sd ciia huylt thanh khdng td djc hifu vd bp sinh

pham chin dodn nhganh vi khudn td 319

nhom 0139, don gid Ogawa, don gid Inaba) dat tieu chudn co sd 319

5.7 San xudt dupe 100 bp sinh phdm chan dodn nhanh vi khudn ta mdi bp 1 test

djt ti6u chudn co sd 319

CHU'ONG 6 KIEN NGHJ 320

TAI LIEU THAM KHAO 321

PHV LVC 330

Phu lyc 1: QUY TRINH CHAN DOAN SCiM BENH TA 331

Phu luc 2: QUY T R I N H DIEU TRI BENH TA 337

Phu luc 3: QUY TRINH DU PHONG BENH TA 350

Phu luc 4: QUY TRJNH XL/LY 6 DICH TA 354

Phu luc 5: HUdNG DAN SIT DUNG CAC HOA CHAT KBIT TRUNG

CHLTA CLO TRONG CONG TAC PHONG C H 6 N G DICH 364

Phu luc 6: PHIEU DIEU TRA B £ N H NHAN TIEU CHAY CAP TINH

NANG 368

Phy luc 7: BQ CAU HOI NGHIEN ClTU BENH CHLTNG 373

Phu lyc 8: SO D 6 C A C B U 6 C DIEU TRA NGHIEN CUU XAC DINH

YEU TO NGUY CO VA NGUON GOC VU DICH 380

Phu lyc 9: BIEN B A N HQP v A KET LUAN CUA HOI D 6 N G Y DlTC 381

Phu luc 10: G I A Y CHLTNG N H A N KIEM DICH DONG V A T NHAP KHAU

382 Phu lyc 11: B A N G MPN CHO 3 ONG 3 NONG D Q 1 ; 0 , 1 ; 0 , 0 1 ml 383

Phu lyc 12: B A N G MPN CHO 3 ONG 3 NONG D Q 0,1; 0,01; 0,001 gam 385

Phu luc 13: T A C H CHIET ADN VI BCHUAN B A N G P H U O N G P H A P

PHENOL - CHLOROFORM 387

Phu lyc 14: KET QUA KHOANH GL\Y K H A N G SINH KHUECH T A N CUA

CAC CHUNG V.cholerae Ol 388

Phu luc 15: KET QUA KHANG SINH DO CUA CAC CHtJNG V.cholerae 01

BANG KY THUAT MIC 389

DANH MVC CAC KY HI$U, CHU" VIET TAT

ADN Acid desoxyribonucleotid

(Deoxyribonucleic acid) AIDS H6i chiing suy giam mien djch mSc ph^i ATCC American Type Culture Collection

Candida Nam Candida

CBTNNDQG Cac benh truyen nhiem va nhiet dai qu6c gia CDC Trung tam kiem soat dich benh Hoa Ky

(Centre for Diseases Control)

C F A Ta duoc Freunds hoan toan

(Complete Freunds adjuvant) CPU Colony Forming Unit

CHO Te bao tning chupt dat vang

(Chinese Hamster Ovary)

CI Khoang tin cay

(Confidence Interval)

Cl.perfringens Clostridium perfringens

CLSI Vien Tieu chuan xet nghifm va lam sang

(Clinical and Laboratory Standards Institute)

Colloidal Gold Chat keo vang

cs Cong SIT

CT Doc td ta

(Cholera Toxin) DCA Thach Deoxycholate Citrate

(Deoxycholate Citrate Agar) DMEM Dulbecco's Modified Agles Medium DMSO Dimethyl sulfoxide

E.coli Escherichia coll

ELISA Thii nghiem mien dich gan men

(Enzyme-linked Immunosorbent Assay)

ER Moi truong ER

FAO To chiic nong luong quoc te

(Food and Agriculture Organization) FDA Co quan Quan ly thuoc va thuc pham, My

(Food Drug Adminitration) GAP Thuc hanh nong nghiep tot

(Good Agricultural Practice) GIS He thong thong tin dia ly

(Geographic Information System) GPS He thong dinh vj toan cau

(Global Position System)

Vi rut gay suy giam miln djch d ngudi

(Human immunodeficiency virus) Hypoxanthine Thymidine Huyet thanh

Td dup'c Freunds kh6ng hoin toan (Incomplete Freunds adjuvant) Khang huyet thanh

Kinh hien vi di?n tii Khuan lac Khang sinh Canh thang LB (Luria Bertani) Lysin decaborxylaza Lipopolysaccharide Lauryl tryptose broth Khang the don dong (Monoclonal Antibody) N6ng dp lie che t6i thieu (Minimum Inhibitory Concentration)

So CO the nhat (Most Possible Number) Vibrio khong ngung ket (Non Agglutination vibrios)

Uy ban Quoc gia v6 Cac tieu chuSn can lam sa (National Committee for Clinical Laboratory Standards)

Mat do quang hpc/Do due

Phong thi nghiem Vi khuan duang rupt Khang hoan toan/Khang trung gian/Nhay cam (Resistance/Intermediate/Sensitive)

Khuyech dai ngau nhien cac doan DNA da hinh (Randomly Amplified Polymorphic DNA)

Ky thuat ngung ket latex thu dong dao ngupc (Revered Passive Latex Agglutination)

Staphylococcus aureus

Moi truong SR Dung dich dem TAE (Tris Aeetat EDTA) Dung dich dem TBE (Tris Borat EDTA) Muoi mat Thiosulfate Citrat (Thiosulfate Citrat Bile Salt) Yeu to xam nhap

Ve sinh Dich te Trung ucmg

World Health Organisation

(T6 chijrc Y tl Thi giai)

Y tl du phong

KY HIEU CUA MQT SO LOAI KHANG SINH

Ampicillin/Sulbactam Azithromycin Cefiiroxime Ciprofloxacin Doxycycline Kanamycin Nalidixic acid Piperacillin Trimethoprim-Sulfamethoxazole

DANH MVC CAC BANG

Bdng 2-1 Trinh tu cdc cdp mdi dung cho phdn ung PCR xdc dinh vi khuan

, ' 73

ta

Bdng 2-2 Cdc cap mdi dung trong phdn img PCR xdc dinh muc dp khdng

khdng sinh ciia cdc chung vi khuan td °'

Bdng 2-3 Dgc diim phdn bi?t typ sinh hpc co dien vd El Tor 95

Bdng 2-4 Mqt sd cap mdi sic dung trong ky thuat PCR xdc dinh dac tinh

CTX cassette ^* Bdng 2-5 Trinh tic mdi trong ky thudt PCR xdc dinh ddc tinh CTX 98

Bdng 2-6 Trinh tu cdc moi sic dung trong ky thugt RAPD IOO

Bdng 2-7 Trinh tu mdi sir dung trong ky thudt PCR gidi trinh tu gen ctxB

103 Bdng 2-8 Trinh tie cdc cap moi dp dung trong nghien cuu vibriophage Ill

Bdng 3-1 Phdn bd theo dia du cdc trucmg hap mdc td mien Bdc, Viet Nam,

2007-2009 125 Bdng 3-2 Thai gian keo ddi cdc dat dich trong vu dich ndm 2007 - 2009

130 Bdng 3-3 Kit qud cdc chiim ca benh td ldm sang tgi Hd Noi xdc dinh bang

phdn mem STatScan 135

Bdng 3-4 Ket qud dieu tra dich te 4 ca binh ddu tien trong cdc d0 dich tit

2007-2009 137 Bdng 3-5 Ty le benh nhdn dn cdc thuc phdm cd nguy ca trong vdng 5 ngay

truac khi khai phdt cua cdc trudng h(ifp mdc td trong 2 tuan ddu

cua cdc dot dich 138 Bdng 3-6 Ty le dn cdc thuc phdm co nguy ca trong vong 5 ngay truac khi

khai phdt bfnh cua cdc truong hap mdc td d giai dogn sau cua

cdc dat dich jsg

Bdng 3-7 Ket qud xet nghiem mdu nuac cdc logi trong 2 tudn ddu cua cdc

dot dich td til ndm 2007 -2009 140

Bdng 3-8 Kit qud xet nghiem mdu nude cdc logi a giai dogn sau ciia cdc

dot dich td tic ndm 2007-2009 141

Bdng 3-9 Ket qud xet nghiem mdu nude dinh ky tie thdng 4/2008 den thdng

3/2009 142 Bdng 3-10 Kit qud xet nghiem mdu rau tham, rau sdng tgi cdc cira hdng

lien quan din benh nhdn td trong 3 dat dich 2007 - 2008 143

Bdng 3-11 Kit qud xet nghiem mdu rau tham, rau sdng tgi cdc cha ddu mdi

144 Bdng 3-12 Kit qud xet nghiem mdu rau tham, rau sdng tgi cdc trgng

trgi/vudn vg viing chuyen canh rau 146

Bdng 3-13 Kit qud xet nghiem mdu rau tham, rau sdng dinh ky tit thdng

4/2008 din thdng 3/2009 147

Bdng 3-14 Kit qud xet nghiem mdu mdm tdm tgi cdc ciia hang lien quan din

binh nhdn td 148 Bdng 3-15 Kit qud xet nghiem mdu mdm tdm tgi cdc cita hdng, chg ddu

mdi, casd sdn xudt 148

Bdng 3-16 Kit qud xet nghiem cdc mdu binh phdm tgi mot sd cira hdng thit

cho trong vu dich ndm 2007 - 2009 149

Bdng 3-17 Hinh thiec cung cdp thit chd cho cdc cua hdng 150

Bdng 3-18 Tinh trgng chd khi mang din cdc cua hdng 150

Bdng 3-19 Kit qud xet nghiem cdc mdu nghi ngd 151

Bdng 3-20 Kit qud lay mdu khu giit md chd vd xet nghiem 154

Bdng 3-21 Ty li mdu ducmg tinh theo diim lay mdu 155

Bdng 3-22 Kit qud xet nghiem mdu phdn chd lay qua tdm bdng ngody hdu

mdn cho tai xd Thdnh Loc 156

Bdng 3-23 Kit qud xet nghiim cdc mdu binh phdm khac tgi xa Thdnh U"^

156 Bdng 3-24 Dgc diim vi ddi tugng vd dia diim nghiin cuu binh chiing 162

Bdng 3-25 Cdc dgc diim nhdn khdu hgc ciig nhdm binh vg nhdm chung 163

Bdng 3-26 Mgt sd yiu td nguy ca liin qugn vdi dich tg trong phdn tich da

biin '64 Bdng 3-27 Biiu hiin ldm sdng cita cdc nhdm chd thitc nghiim 165

Bdng 3-28 Thai gian ddo thdi vi khudn tg ra phdn cua chd sau khi gdy

nhiim '"6 Bdng 3-29 Ty li ngudi lanh mang vi khudn td d trong 6 dich cd ngudi lanh

mang trimg 167 Bdng 3-30 Kit qud xet nghiim vi sinh vdt trong mdu mdm tdm thucmg phdm

175 Bdng 3-31 Kit qud nudi cdy phdn ldp trin mdu mdm tdm thii nghiim / 76

Bdng 3-32 Thdng tin vi sd lugng vd dia diem cua chung nghien cuu 179

Bdng 3-33 Kit qud khoanh gidy khdng sinh khuich tdn ciia cdc chiing V

cholerae 01 180 Bdng 3-34 Kit qud khdng sinh do cua cdc chung V.cholerae Ol bdng ky

thudt MC 181 Bdng 3-35 Kit qud khdng sinh do vd gen khdng khdng sinh cua cdc chung vi

khudn td 182 Bdng 3-36 Kit qud dinh lugng dgc td td cua cdc chung V.cholerae Ol 184

Bdng 3-37 Phdn bd tudi cua cdc binh nhdn mdc td miin Bdc, Viit Nam,

2009 185 Bdng 3-38 Phdn bd vi nghi nghiip 186

Bdng 3-39 Phdn bd vi dia du hdnh chinh 187

Bdng 3-40 Ty U binh nhdn cd binh mgn tinhphdi hgp 188

Bdng 3-41 Tylicdc logi thicc dn nghi ngd truyin binh 189

Bdng 3-42 Thdi gign nhdp viin tie khi cd triiu chiing ddu tiin 191

Bdng 3-43 Cdc biiu hiin ldm sdng khi nhgp viin 192

Bdng 3-44 Ty li binh nhdn cd cdc bien chimg 193

Bdng 3-45 Thay dd ve huyit hgc d binh nhdn td 194

Bdng 3-46 Thay do creatinin mdu a binh nhdn td 195

Bdng 3-47 Thay ddi vi khi mdu a binh nhdn td 196

Bdng 3-48 Thay ddi Kali mdu d binh nhdn td 196

Bdng 3-49 Ket qud dinh typ sinh hgc 198

Bdng 3-50 Trinh tu cdc a xit amin trong tiiu phdn B cua dgc td td tuang ting

vdi trinh tugen ctxB 211

Bdng 3-51 Kit qud NAG phdn ldp tic mdu nude be mg 215

Bdng 3-52 Kit qud phdn lap Vibriophage tie mdu ggc tdm 276

Bdng 3-53 Ket qud kiiu hinh vibriophage tgi Hdi Phdng vd Thdi Binh (Quan

sdt dudi KHVDT) 218

Bdng 3-54 Kit qud phdt hiinfsl,fs2 tgi Hdi Phdng vd Thdi Binh 221

Bdng 3-55 Kit qud phdt hiin kappa phage tgi Hdi Phdng vd Thdi Binh 222

Bdng 3-56 Ty le benh nhdn duac bii dich trudc khi din viin 223

Bdng 3-57 Ty li binh nhdn sie dung cdc biin phdp bil dich tgi nhd 224

Bdng 3-58 Lien quan giiig bii dich tgi nhd vd natri mdu khi vdo viin 225

Bdng 3-59 Lien quan giiig bii dich tgi nhd vd kgli mdu khi vdo viin 225

Bdng 3-60 Anh hudng cua bii dich dudng udng trudc khi vdo viin vd ty li

sdc 226 Bdng 3-61 Lugng ORS chi dinh hdng ngay trong binh viin 226

Bdng 3-62 Tuang quan dich truyen vd ORS udng 227

Bdng 3-63 Sd lugng dich truyin dich trong gid ddu 2^'

Bdng 3-64 Sd lugng dich truyin trong ngdy ddu 2^° Bdng 3-65 Sd lugng cdc logi dich truyin trong cdc ngdy 228

Bdng 3-66 Anh hudmg cua truyin dich din Natri mdu 229

Bdng 3-67 Anh hudng ciia truyen dich din kali mdu 229

Bdng 3-68 Anh hudng ciia truyin dfch din pH mdu binh nhdn cd sdc 230

Bdng 3-69 Anh hudng ciia truyin d\ch din pH mdu binh nhdn khdng s6c230

Bdng 3-70 Ty li binh nhdn dugc diing thudc trudc khi vdo viin 231

Bdng 3-71 Mice dg nhgy cdm vdi khdng sinh dua vdo MIC (E-test) 233

Bdng 3-72 Kiiu di khdng cua V.cholerae Ogawa ndm 2008 234

Bdng 3-73 So sdnh su khde biit vi ty li nhgy cdm vdi khdng sinh cOa cdc

chiing V cholerae Ol Ogawa bdng 2 phuang phdp 235

Bdng 3-74 So sdnh su khde biit vi ty li trung gian cua cdc chiing

V.cholerae Ol Ogawa bdng 2 phuang phdp 236

Bdng 3-75 So sdnh su khde biit vi ty li khdng ciig cdc chiing V.cholerae Ol

Ogawa bdng 2 phuang phdp 236 Bdng 3-76 Thdi gian hit tiiu chdy sau khi dimg khdng sinh 237

Bdng 3-77 So ngdy diiu tri di cdy phdn benh nhdn trd ve dm tinh 238

Bdng 3-78 Thdi gian sgch vi khudn td sau khi dimg khdng sinh 239

Bdng 3-79 Anh hudng cua dg tudi din thdi gian ndm viin 239

Bdng 3-80 Anh hudng cua do tudi din thdi gian hit tiiu chdy 240

Bdng 3-81 Anh hudng cua dg tudi din thai gian cdn vi khudn trongphan240

Bdng 3-82 Ty li binh nhdn td cd biin chiing 240 Bdng 3-83 Anh hu&ng cOa gidi din thai gian ndn viin, thdi gian cdn tieu

chdy, thdi gian cdn vi khudn td trongphdn 241

Bdng 3-84 Anh hudng cug gidi din ty li biin chimg 242

Bdng 3-85 Anh huang cua binh nin din thdi gian cdn tieu chdy 242

Bdng 3-86 Ty li binh nhdn diing thudc chdng tieu chdy trudc khi den viin

243 Bdng 3-87 Anh hudng ciia thudc chdng tieu chdy den tinh trgng mdt nude

244 Bdng 3-88 Anh hudng cua thudc chdng tieu chdy den thai gian ndm vien

245 Bdng 3-89 Anh hudng cua thudc chdng tieu chdy din thdi gian tieu chdy 245

Bdng 3-90 Anh hudng ciia thudc chdng tiiu chdy din thai gian cdn vi khudn

td trong phdn 246 Bdng 3-91 Anh hudng cua thudc chdng tieu chdy din biiu hien chudng

bung 246 Bdng 3-92 Ty li benh nhdn cd diin biin ndng 247

Bdng 3-93 Ty li binh nhdn cd suy thdn 247

Bdng3-94 Cdc biin phdp xie tri suy thdn 248

Bdng 3-95 Xu tri toan hda mdu sau khi binh nhdn da thoat sdc 249

Bdng 3-96 Xu tri hg kali mdu 249

DANH MVC CAC H ! N H

Hmh 1-1 Phdn bd dich td trin thi gidi ndm 2008 ^2

Hinh 1-2 Sa dd cdu true ciia CTX cassette ^6

Hinh 1-3 Sa do cdu true ciia RSI va RS2 37

Hmh 1-4 Su luu hdnh ciia vi khudn td d mdi trudng vd d ngudi 39

Hinh 2-1 Sa dd thirc hiin phuang phdp MPN 69

Hmh 2-2 Cdch dgc kit qud phuang phdp MPN 70

Hinh 2-3 Khudn lgc E.coli tren mdi trudng Endo 71

Hmh 2-4 Tinh chdt sinh hda ciia E.coli 72

Hmh 2-5 Sa dd quy trinh cdy thic nghiim sye thich ung cua vi khudn td

trong mdm tdm 79 Hinh 2-6 Kit qud ducmg tinh cdc miic dg 86

Hinh 2-7 Chudn bi mdu ggc tdm 104

Hinh 2-8 Hinh dnh dgt vd thu thgp mdu ggc tdm 108

Hinh 2-9 Sa do phdn ldp vibriophage theo phuang phdp cua Shimidori 109

Hinh 3-1 Bdn do phdn bd cdc ca binh td tgi Hd Ngi trong 2 tudn ddu tiin

ciia Vlf dich 2007 - 2009 120

Hinh 3-2 Bdn do cdc tinh cd binh nhdn mdc td theo tiing d0 dich ndm

2007-2009 126 Hinh 3-3 Bdn do dia diim thttc hiin nghien ciiu 131

Hinh 3-4 Bdn dd phdn bd cdc ca binh td tgi Hd Ngi theo kit qud GPS

trong thdi gian ddu cua vu dich 10/2007 - 04/2008 752

Hinh 3-5 Bdn do phdn bd mice do tgp trung cdc ca binh td tgi Hd Ngi theo

kit qud GPS trong thdi gian ddu cua v^ dich 10/2007 - 04/2008

133

Hinh 3-6 Bdn do phdn bd cdc chiim ca binh td ldm sdng tgi Hd Ndi sti

dung phdn tich khdng gian thdi gian ddu cua vu dich 10/2007

-04/2008 134 Hinh 3-7 Bdn dd phdn bd cdc ca binh td tgi Hd Ngi theo quy md

xd/phudng dgt dich td 1 vd 2 135

Hmh 3-8 Bdn do phdn bd cdc ca binh td tgi Hd Ngi theo quy md

xa/phudng dgt dich td 3 vd 4 136

Hinh 3-9 Bdn dd mgng ludi phdn phdi thit chd lir mdt Id md tgi

Duang Ndi vd su xudt hiin cdc ca benh td tren dia bdn Hd Ngi

ndm 2008 154 Hinh 3-10 Trai nudi chd tap trung tgi Thanh Lgc, Hdu Lgc, Thanh Hda 157

Hmh 3-11 Bdn do dudng nhdp khdu chd tie Lao vdo Viit Nam qua ciia khdu

Cdu Treo, Hd Tinh 159

Hinh 3-12 Xe chd chd ciia cdng ty nhgp khdu tgi Trgm kiim dich ddng vdt

Cdu Treo, Hd Tinh 160

Hinh 3-13 Thuyin chuyin chd nhgp khdu vdo ndi dia Viet Nam 161

Hinh 3-14 Chuyin chd tiexe cita Lao sangxe ciia Viet Nam 161

Hinh 3-15 Chd mdc td diin hinh, mdt nude vd chit sau khi gdy nhiem thuc

nghiim 165 Hinh 3-16 Kit qud diin di sdn phdm phdn ting PCR da mdi phdt hiin vi

khudn td trong mdm tdm 174

Hinh 3-17 Kit qud diin di sdn phdm phdn iing PCR da mdi phdt hiin vi

khudn td trong mdu mdm tdm thienghiem 178

Hinh 3-18 Kit qud dgi diin cdc gen khdng khdng sinh vd yiu td SXT ciia vi

khudn td 182 Hinh 3-19 Phdt Men gen ctxA bdng 1^ thudt PCR 184

Hinh 3-20 Hinh dnh ky thudt RPLA xdc dinh ndng dd ddc td td cda

V.cholerae Ol 184

Hinh 3-23 Kit qud PCR xdc dinh logi gen rstR

Hmh 3-24 Sadd trinh tu RSI vd CTX cgssette

Hinh 3-25 Kit qud PCR xdc dinh trinh tu RSI vd CTX cassette 202

Hinh 3-26 Anh diin di cua ky thuat RAPD vdi cdc mdi dan 204

Hinh 3-27 Ba logi kiiu gen RAPD ^^^

Hinh 328 Hmh dnh PFGE chiing td phdn ldp tgi Viit Nam giai dogn 2007

-2009 ^'^^

Hinh 3-29 Hinh dnh PFGE chiing tdphdn ldp tgi Viit Nam vd Lao 206

Hinh 3-30 Hinh dnh PFGE so sdnh chiing td phdn Igp tgi Viit Nam gitn

dogn 2007 - 2009 vd trudc do 206

Hinh 3-31 So sdnh kiiu gen PFGE cdc chiing Viit Nam vd Lao 208

Hinh 3-32 So sdnh kiiu gen PFGE cdc chimg theo dia diem vd thai gian 209

Hmh 3-33 Kit qud gidi trinh tu cua gen ctxB 210

Hinh 3-34 Kit qud PCR phdt hiin gen VCOl, VC0139 clxA a nuac be ni«t

tgi Hdi Phdng (thdng 2/2009) 213

Hinh 3-35 Kit qud PCR phdt hiin gen VCOl, VC0139 ctxA a nuac bi rtigt

tgi Thdi Binh (thgng3/2009) 214

Hmh 3-36 Kit qud PCR phdt hiin gen ToxR cua NAG phdn Igp a mdi

trudng nude bi mgt 216

Hmh 3-37 Hinh dnh plaque cita vibriophage 216

Hinh 3-38 Hinh dgng (dgi diin) cua vibriophage phdn lap tgi Hdi Phdng

218 Hinh 3-39 Hinh dgng (dgi diin) cita vibriophage phdn Igp tgi Thai Binh 219

Hinh 3-40 Hinh dgng cdc phage chudn quan sdt dudi KHVDT ^20

Hinh 3-41 Kit qud PCR phdt hiin fs! vdfs2 220 Hinh 3-42 Kit qud PCRphdt hiin kappa phage tgi Thdi Binh 221

Hinh 3-43 Ket qud PCR phdt hiin kappa phage tgi Hdi Phdng 222

DANH MVC CAC BifiU D 6

Biiu dd 1-1 Tmh hinh dich td tren thi gidi tit ndm 2000 din 2008 31

Biiu dd 1-2 Sd ca td tich luy trong cdc thdi ky 5 ndm trin thi gidi

2000-2008 ^' Biiu do 1-3 Diin biin dich td d Viit Nam 1996 - 2008 33

Biiu dd 3-1 Phdn bd cdc ca mdc mdi theo ngdy khdi phdt trong 2 tudn ddu

tiin (tic 23/10 din 5/11/2007) 118

Biiu dd 3-2 Phdn bd binh nhdn mdc theo dig du trong 2 tudn ddu tiin 119

Biiu dd 3-3 Diin biin dich theo dia du vd thdi gian trong 2 tudn ddu tien

119 Biiu do 3-4 Diin bien dich td theo ngdy khdi phdt todn bg vu dich d mien

Bdc ndm 2007 - 2009 120

Biiu do 3-5 Sd ca mdc td trung binh ciia 4 dgt dich theo thdng

(2007-2009) 121 Biiu do 3-6 Diin biin dich theo ngdy khdi phdt theo thdng dm Uch trong

thdng ddu tiin ciia cdc dgt dich 122

Biiu do 3-7 Diin biin dich theo ngdy khdi phdt theo thdng dm Uch trong

thdng ddu tien theo cdc dgt dich 123

Biiu do 3-8 Sd ca mdc, sd ca tic vong vd quy md dich theo dia du trong

cdc dgt dich td, mien Bdc, 2007 - 2009 123

Bieu dd 3-9 Phdn bo ca binh theo dia du ciia vu dich ndm 2007 - 2009 tgi

miin Bdc, Viet Nam 124

Biiu do 3-10 Su phdn bd cdc trudng hgp mdc td theo liia tudi a miin Bdc

Viet Nam, ndm 2007 - 2009 127

Bleu do 3-11 Suphdn bd cdc trudng hgp mdc td theg liia tudi theo cdc dgt

dich, miin Bdc Viit Nam, nam 2007-2009 127

ddu tiin ciia cdc dgt dich miin Bdc, 2007 - 2009 128

Biiu do 3-13 Sit phdn bd cdc trudng hgp mdc td theo gidi trong cd 4 dot

Biiu do 3-17 Tile Vo NAG ducmg tinh phdn lap tie mdu rau 169

Biiu do 3-18 Ti li % NAG ducmg tinh phdn lap tir mdu dgng vdt giap xdc

170 Biiu do 3-19 Miec do d nhiim coliform nude bi mat 171

Biiu do 3-20 Mice do d nhiim E.coli trong rau 171

Biiu do 3-21 Miic do d nhiem E coli trong dgng vat giap xdc 172

Biiu dd 3-22 Phdn bd vi gidi 186

Bieu dd 3-23 Phdn bd binh nhdn vdo vien dgc theo thdi gian dich 187

Bieu dd 3-24 Diin biin vetyle% thiec dn nghi ngd truyin binh 190

Bieudd 3-25 Thdi gian ii benh ciia cdc benh nhdn 191

Bieu dd 3-26 Tinh chdt phdn ciia binh nhdn td 192

Biiu dd 3-27 Sd Idn benh nhdn tieu chdy trong 5 ngdy ddu 193

Biiu do 3-28 Tyle binh nhdn cd sdc khi nhdp viin 194

Bieu dd 3-29 Ty li benh nhdn cd ndn, budn ndn 224

Biiudd 3-30 So lugng cdc logi dich truyen trong 5 ngdy ddu 228

Bieudd 3-31 Tuang quan giiia pH mdu vdi kali mdu 231

Biiu do 3-32 Tyle cdc logi khdng sinh diiu tri td dd dugc diing 232

Biiu dd 3-33 Sd ngdy ndm viin cua binh nhdn td 238

Biiu do 3-34 Ty li binh nhdn cd ndn/budn ndn d cdc binh nhdn dimg thuoc

chdng tiiu chdy 243 Biiu dd 3-35 Mice dg tiiu chdy d cdc binh nhdn diing thudc chong tieu chdy

' 244

MODAU

Ta la mpt benh truyen nhiem cap tinh do vi khuan ta (V.cholerae) nhom

01 va 0139 gay ra Benh lay theo dudng tieu hoa chii yeu do an phai thiic an hoac nude uong bi 6 nhiem vdi vi khuan ta Cac trieu chiing chinh ciia benh la tieu chay toe nude cap tinh dan tdi mat nude va roi loan dien giai tram trpng Benh ta lay lan nhanh va co kha nang gay thanh djch Idn vdi ty le tu vong cao, dac biet la tai cac nude ngheo [3] Trong vong 200 nam qua, ta da gay ra

7 vu dai dich tren the gidi lam hang chuc trieu ngudi tu vong Cho den ngay nay, dich ta van Imi hanh khap the gidi va la mot trong nhung nguyen nhan gay tii vong cao tai nhieu quoc gia Nam 2007, tong so ca mac ta tren toan the gidi la 177.963, trong do cd 4.031 trudng hpp tu vong da ghi nhan tai 53 quoc gia; ChSu A chilm 6,4% vdi 11.325 ca mdc, chet 24 [109] Trong nam 2008, mpt vu dich ta Idn da xay ra tai Zimbabwe vdi 16.141 ca nghi ngd mac benh,

775 trudng hpp tu vong (ty le chet/mdc la 4.8%) Thang 8 nam 2008, dich ta ciing xay ra tai Iraq lam 341 ca mac, 5 ca tii vong [111] Theo so lieu ciia To chiic Y te the gidi so lupng cac vu dich ta va so ca mac ta co xu hudng tang trong nhiing nam gan day Khi phan tich so lieu theo timg giai doan 5 nam cho thay xu hudng toan cau ciia benh ta tang len mot each deu dan ke tir dau thien nien ky Tir nam 2004 den nam 2008, so cpng don cac ca benh thong bao cho TCYTTG la 838.315 ca, trong khi con so nay d giai doan tir nam

2000 den 2004 chi la 676.651 ca Nhu vay trong 5 nam gan day so ca benh ta

da tang len 24% [111]

V.cholerae co the cu tni tu nhien d trong cac dong vat giap xac va cac thuc

vat thuy sinh, chu yeu d vimg ciia song va ven bien va ddng vai trd quan trpng trong duy tri lau dai cac vu dich ta Bang phuong phap phat hien dau vet phan tii (moleeular fingerprinting) cd the xac dinh sy lan truyen cua chiing ta gay benh, so sanh danh gia mdi lien quan giua cac chiing gay dich cua cac viing

25

va thdi gian khac nhau trong mot nude, giira cac qu6c gia, vd cac luc

di^-dd xac dinh ngudn goc, dudng lan truyin cua djch ta [32],[6I],[100] Ngoai

ra, djch te hpc phan tir co thi giup cho tra ldi cdc van dl quan trpng nhu ngudn lay, tinh trang Ian trayin, tinh khdng thuoc cua cdc chung gay bfnh Giam sat chu dpng su tin tyi cua vibrio va vibriophages d moi trudng nude

ngoai canh, la ca sd dl xuat cac chi so dy bdo djch tk tmdc khi xuat hifn cdc

trudng hop benh nhan, giup cho cdng tac phdng chong djch ta chu dpng, kjp thdi va hifu qua

Bfnh ta la nguyen nhan gay tiiu chdy d p quan trpng d Vift Nam hon mpt thi ky qua vdi nhieu vy djch Idn xay ra trong ljch sii dupe ghi nhan Djch ta d Vift Nam trong nhihig nSm trudc dSy dupe xdc djnh Id do chiing phay khuan

ta xam nhap nhu vy djch td ndm 1937 - 1938 xdy ra d mien Bdc (Hdi Phong, Mdng Cai), cd so mdc len tdi 20.687 ngudi, tii vong khodng 70%, djch td nam

1964 cd tren 20.000 ngudi mdc da s6 cdc trudng hpp a Bdc Trung Bp vd Nam

Trang Bp Cho din nay, d miln Nam, miln Trung bfnh ta thudng xdy ra dudi dang djch luu hanh dia phuang, con d mien Bac van chua cd bdng chiing khdng dinh bfnh ta luu hanh dia phuang [3],[7] Trudc nam 2005, djch td xudt hien rai rac d mot sd tinh miln Bdc nhimg rat nhanh chong dupe khong che Sau 2 nam 2005 - 2006 khdng ghi nhan ca mdc ta ndo tren toan quoc, bat ngd tir ndm 2007 dich td da lien tilp xdy ra t?i nhilu tinh, thdnh pho phia Bac vdi hang nghin ca mdc gay anh hudng Idn din siic khde ngudi dan vd ddi song kinh te xd hdi Djch dien bien phirc tap vd khdng giong vdi cdc vu dich xay ra trade day: bfnh xdy ra vao miia ddng, cdc ca bfnh xuat hifn tan phat tren difn rdng nhtmg ddn dap vdo cimg mpt thdi dilm, khdng lien quan den nhau Bfnh td luu hanh d Vift Nam tir lau da gdy nhieu thiet hyi ve ngudi ciing nhu ve kinh te xa hpi Trudc ddy da cd nhiing nghien ciiu v l cdc ITnh vuc: dilu tra djch te hpc, xac dinh tinh khang khdng sinh, san xuat vac-xin ta, ddnh

gia hifu lyc cua vac-xin va thii nghiem mdt so ky thuat chan doan trong phdng thi nghiem da gdp phin dang kl trong cdng tac phong chdng dich tai nude ta Tuy nhien, van chua co nhiing nghien cim sau mang tinh chdt he thdng, toan difn ve dich te hpc, dich te hpc phan tir, sinh thai hpc, lam sang bfnh ta ciing nhu viec phat trien cac sinh pham chan doan benh ta

De tai nghien cuu khoa hpc cap nha nude "Nghien ciru dac fliem dich

te hpc, lam sang benh ta va de xuat giai phap phong chong djch a Viet

Nam" da dupe giao cho Vien Ve sinh Dich te Trung uong thuc hien vdi muc

dich chung la xac dinh dac diem dich te hpc, lam sang benh ta d Vift Nam, de xudt mdt sd giai phap phong chdng dich ta, phat trien sinh pham va bd sinh phdm chan doan nhanh nham khdng che su lay lan cua dich, han che tdc ddng xau ctia bfnh dich den tinh hinh kinh te, xa hdi

17

MVC TIEU NGHIEN CUtJ

D I tai dupe thyc hifn vdi cdc myc tieu sau:

1 Xac dinh dac diem djch tl hpc va lam sang bfnh td

2 Xac djnh dac diem djch te hpc phdn tur vd dp dyng trong dy bdo djch

3 Nghien cihi hoan thifn quy trinh chin dodn vd dieu trj bfnh ta

4 Nghien cim hoan thifn quy trinh xir ly 6 djch vd dy phdng bfnh td

5 Nghien curu xay dyng quy trinh sdn xuit huylt thanh khdng td d|c hifu

d qui md phdng thi nghifm

6 Nghien cim xdy dung quy trinh sdn xuat bp sinh pham chan doan nhanh

vi khuan ta d qui md phdng thi nghifm

7 Nghien curu xay dung tieu chuan ca sd ciia huylt thanh khdng td dac

hieu va bd sinh pham chan doan nhanh vi khuan ta

8 San xuat 3000 mau huyet thanh khang td mdi loai (da gia nhdm OI, da gid nhdm 0139, dan gid Ogawa, don gia Inaba,) dat tieu chuan ca sd

9 San xuat 100 bp sinh pham chan dodn nhanh vi khuan td (moi bd 1 test)

dat tieu chuan co sd

Bao cao toan van se dugrc trinh bay lam 2 t|p nhv sau:

- Tap 1: Tdng quan, phuong phdp, kit qud nghien curu, ban luyn va kit

luan cua cac muc tieu 1, 2, 3 vd 4

- Tap 2: Tdng quan, phuong phdp, kit qua nghien ciiu, ban lu|n va kit ludn cua cdc muc tieu 5, 6, 7, 8 va 9

CHl/OfNG 1 T O N G QUAN

1.1 Tinh hinh nghien cmi ngoai niro'c lien quan den de tai

Bfnh ta dupe ndi den tir thdi Hippocrates va Sanskrit va dupe md ta Idn ddu tien bdi Garcia del Huerto nam 1563 vd dupe John Snow chiing minh dupe vai trd lay trayen cua nude nam 1849 [3] Tuy nhien, den dai dich lan thur 5 tac nhan gay bfnh mdi dupe phat hifn; tiep do, nam 1905 ngudi ta da

xac dinh dupe chiing vi khuan ta mdi la V.cholerae Ol [90],[58] Nam 1992, chiing V.cholerae 0139 Bengal lan dau dupe phat hien tai Bang-La-Det Sau

dd vdo nam 2002 chung vi khuan nay da gay ra dich Idn vdi khoang 30 nghin ngudi mic d Dhaka, Bang-La-Det Nhu vay chimg 0139 va chimg Ol ciing tdn tai song song d An Dp va Bang-La-Det Mac dil, chiing 0139 mdi xuat hifn lin dau tien d Nam A, nhung da nhanh chdng trd thanh luu hanh dia phuang va Id nguyen nhan gay ra cac vu dich Idn d khu vuc nay [52],[92],[110]

td:

Trong vdng gan 200 nam qua loai ngudi da trai qua qua 7 vu dai djch

• Dai dich ta lan thii nhat (1816 - 1826): Bat dau tir Bengal sau lan sang An Dd, Trang Qudc va bien Caspian

• Dai dich ta lin thii hai (1829 - 1851): Ciing bit diu tir Bengal Nam 1831 dich lan sang London (6.536 ngudi chet), Paris (20.000 ngudi chet trong tdng sd 650.000 dan), tdng sd chet toan nude Phap la 100.000 Sau dich lan sang Nga, Quebec, Ontario va New York

• Dai djch ta lan thii ba (1852 - 1860): Xay ra d nhieu vimg ciia Nga, lam hang trieu ngudi chit 6 London, dich lam 10.738 ngudi chit Djch xay ra d Chicago lam chet 5,5% dan sd

29

• Dai djch td Ian thir tu (1863 - 1875): Djch xdy ra chii ylu d '^^^^

Au va Chau Phi Djch xay ra d London Idm chet 5.596 ngu^'

• Dai djch td lin thir ndm (1881 1896): Ndm 1892 djch xdy ra d

Hamburg lam 8.600 ngudi chit Day Id vy djch nfing nl cuoi ciing

d Chdu Au

D?i djch td lan thir sdu (1899 - 1923): Djch d Chau Au gidm di do cdc dieu kifn vf sinh tot han nhung djch van xdy ra nJng ne d cdc

thdnh pho ciia Lien Xd

• Dyi djch td lan thir bdy (1961 - nay): Djch bdt dau d In-do-nS-xi-a vdi chung vi khuin El Tor, sau lan sang Bdng-La-Det (1963), An

Dp (1964), Lien Xd (1966) Tir Bdc Phi djch lan sang Italy ndm

1973, Nhdt Bdn va Nam Thdi Binh Duong Djch tiep tyc lan tdi chau My La tinh tir ndm 1991 Sau gin mpt the ky vdng m$t t?i khu vuc nay Cac vu djch biing phdt dpc theo bd bi6n Thai Binh Duong cua Pe ra vd nhilu qudc gia khac trong khu vvrc Tdi ndm

1994 khodng 1 trifu ngudi mdc td da dupe ghi nh$n t^i Chdu N$

La tinh

Do sd lupng ngudi mdc vd chet trong cdc vy d^i djch ta rat cao nen bfnh td dupe xem la mpt trong nhihig tham hpa sire khoe c$ng ddng vd bit bupc phdi bdo cao cung nhu can cd sy can thifp ciia chinh quyln [90],[58] Ndm 2005 tren todn thi gidi cd 131.943 tnrdng hpp mdc ta, trong do cd 2.272 tnidng hpp tii vong (1,72%) tip tnmg chu ylu d Chau Phi [110] Ndm

2007 tdng so ca mdc td tren toan thi gidi Id 177.963, tii vong 4.031 ghi nhfn t?i 53 qudc gia Trong dd, Chau A chilm 6,4% vdi 11.325 ca mdc, chet 24 [109] Trong nam 2008, cd so ca bfnh vd so qu6o gia bdo cdo ca bfnh cho T 6

chtic Y tl thi gidi (WHO) diu tdng so vdi ndm 2007 Nam 2008, WHO da ghi

Biiu dd l-I Tmh hinh dich td tren the gidi tir ndm 2000 din 2008

nhan tdng cdng 190.130 ca benh, trong sd do cd 5.143 ca tir vong, chiem ty le 2,7% Tong sd ca bfnh bao cao da tang len 7,6% va tdng sd ca tir vong dupe bao cao ciing tang len 27% so vdi nam 2007 [111] Khi phan tich so lieu theo timg giai doan 5 nam cho thay xu hudng toan cau ciia benh ta tang len mdt each deu dan ke tir dau thien ky Tir nam 2004 den nam 2008, sd cpng ddn cac

ca benh thdng bao cho TCYTTG la 838.315 ca, trong khi con sd nay d giai doan tir nam 2000 den 2004 la 676.651 ca, nhu vay trong 5 nam gan day sd ca bfnh ta da tang len 24% (Bilu dd 1-2)

lygmn: lleckly EpidmtlohglcillXecitnl, imo, jVo Jl, 2009, SJ, 309-324)

Biiu do 1-2 Sd ca td tich liiy trong cdc thdi ky 5 ndm trin thi gidi,

2000-2008

31

Tinh tren toan the gidi, sd ca tii vong da tdng tir 4.031 ca trong n^"'

2007 Ien 5.143 ca trong nam 2008, ndi mpt each khde so ca tii vong <^^ ^ 8 len 24% va ty If tir vong do bfnh ndy tdng 2,7% Trong t^ng so ca tu vong,

98% dupe bao cdo tir Chau Phi

Suot nira sau cua the ky 20, djch te hpc binh t;i da ghi nli.in iilmng mdc quan trpng sau: (1) Sy lan trayen tren todn the gicri cii.i vu dich ui lan thir 7 la

do vi khuan ta 01 typ sinh hpc El Tor gdy ra tir nam 1961; (2) Phat hien ra cac d chu'a ty nhien cua bfnh td trong nude d viing bii biC-n ciia s inh Bengal

va dpc theo dudng bd bien nude MJ d vjnh Mexico; va {3} su xuat hien lan diu tien cua nhihig vy djch ta biing phdt gdy ra bdi typ 01.39 [45]

.\

>»iii.-6"' N^BJ^iftv, ,

• So ca benh ta xam nhap

Ty le hi vong (%)

Hinh 1-1 Phdn bd dich td tren thi gidi nam 2008

(ngudn: IVeekly epidemiological record, i\o 31 31 Jttlv 20091

1.2 Tinh hinh nghien cihi trong nude lien quan d^n d l tai

Han 1 thi ki qua, bfnh td Id mpt trong nhimg nguyen nlian gay tieu chdy quan trpng tai Vift Nam Nam 1885, mpt vu dich ta da xay ra trong mdt dan vj qudn dpi Phap, ty If tu vong tdi 50% Tir nam 1910 - 1938, hang nam

sd bfnh nhdn mdc ta dupe thdng bao dao ddng tir 5.000 - 30.000 ngyoi [3]

Nam 1937 - 1938, dich ta tir Hdng Kdng theo dudng biln xam nhap vao mdt

sd tinh phia Bac nhu Hai Phong, Quang Ninh (Mdng Cai) Tir dd djch lan theo dudng sdt va duomg bd tdi nhieu tinh ddng bdng Bdc va Trang Bp, sd mdc len tdi 20.687 trudng hpp, trong dd sd chet la 14.992 ngudi (ty If tii vong 70%) Vu dich ta Idn nhat d Viet Nam vao nam 1964 la md diu cho su xam

nhap dai djch ta lan thur 7 vao Mien Nam Viet Nam do V.cholerae typ sinh

hpc El Tor gay ra vdi sd ngudi mac len tdi 20.009 ngudi va 821 tir vong TCr

do den nay d mien Trung va mien Nam, bfnh ta xay ra dudi dang lim hanh dia phucmg Hang nam co hang tram benh nhan mac ta dupe thdng bao Tai mien Bac cho den nay van chua cd bang chimg khang djnh la bfnh ta luu hdnh [3],[15]

Biiu dd 1-3 Diin biin dich td d Viet Nam 1996 - 2008

Tir nam 2000 tdi nay nude ta van cd rdi rdc cdc trudng hpp td tuy nhien bfnh khdng bimg phat thanh dich Idn, cu the nhu sau:

• Nam 2000: 176 frudng hpp mdc, 2 tradng hpp tii vong tai 4 tinh/thanh phd

• Nam 2001:16 tradng hpp mdc, khdng cd tii vong

• Nam 2002: 321 tradng hpp mdc, khdng cd tur vong t^i 18 tinh/thdnh phd

• Nam 2003: 343 trudng hop mdc, khdng cd tur vong t?i 11 tinh/thdnh phd

• Nam 2004: 67 trudng hpp mdc, I tir vong tai 12 tinh/thdnh pho Sau 2 nam 2005 - 2006 khdng ghi nhdn trudng hpp mdc td nao, tir thang 10 ndm 2007 dich td bat ngd xuit hifn trd lai d Mien Bdc vdi nhieu dot djch Nhihig ca bfnh dau tien dupe ghi nhan d Hd Npi vd rat nhanh chdng lan

ra nhieu tinh/thdnh phd mien Bac vdi hang ngdn tradng hop mdc

1.3 Sac diem sinh hoc cua vi l(huan ta

1.3.1 B$c diem vi sinh vat hpc

Nam 1883, R Kock da phan lap dupe vi khuan ta tir phdn ngudi bfnh vd tir niem mac rapt cua nhung xac chet vi bfnh td

Phdy khudn ta Vibrio cholerae (V.cholerae) thupc gidng Vibrio, hp

Vibrionaceae Vi khuan hinh que hoi cong, hinh dau phdy dai tir 1 - 3 (xm,

rdng tir 0,3 - 0,6 |im [6],[1], Gram dm, khdng cd vd, khdng sinh nha bdo, cd mdt long d ddu vd cd khd nang di dpng rit m?nh Phly khudn td di nudi cdy trong mdi tradng ngheo dinh duong, pH kilm (pH 8,5 - 9,5 ) va ndng dp

NaCl cao (3%) V.cholerae cd siic dl khang ylu vdi cdc tdc nhan ly hod (trir

pH kilm), di bj tieu dift d nhiet dp (80°C/5 phiit), bdi hoa chat (Clo lmg/lit/15 phiit) va mdi tradng axit Khd hanh, anh ndng mat trdi ciing lam chit phdy khuan td, tuy nhien, chiing cd thi t6n tyi lau trong phdn, ddt Im,