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THAI NGUYEN UNIVERSITYTHAI NGUYEN UNIVERSITY OF AGRICULTURE AND FORESTRY NGUYEN MANH CUONG INVESTIGATING SOME BIOLOGICAL CHARACTERISTICS OF STREPTOCOCCUS SUIS CAUSING PIG DISEASES IN THA

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THAI NGUYEN UNIVERSITY

THAI NGUYEN UNIVERSITY OF AGRICULTURE AND FORESTRY

NGUYEN MANH CUONG

INVESTIGATING SOME BIOLOGICAL

CHARACTERISTICS OF STREPTOCOCCUS SUIS CAUSING PIG DISEASES IN THAI NGUYEN PROVINCE AND MANUFACTURING AUTOVACCINE FOR PREVENTION

Major: Parasitology & Veterinary Microbiology Code : 9.64.01.04

SUMMARY OF DOCTORAL THESIS

THAI NGUYEN - 2019

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This thesis was completed at:

THAI NGUYEN UNIVERSITY OF AGRICULTURE AND FORESTRY

Scientific advisors: 1 Assoc Prof Dr To Long Thanh

2 Dr Nguyen Van Quang

Thai Nguyen University

At hour, on date month year

The thesis can be found at Libraries:

- National library of Viet Nam

- Thai Nguyen University of Learning Resource Center

- Library of Thai Nguyen University of Agriculture and Forestry

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LIST OF PUBLICATION RELATED TO THE THESIS

1 Nguyen Manh Cuong, To Long Thanh, Nguyen Van Quang, DoHong Anh (2018), "Determination of some biological

characteristics of Streptococcus suis caused disease in pigs in Thai Nguyen province", Veterinary Sciences and Techniques

Magazine, 25(6), pp 36 - 42.

2 Nguyen Manh Cuong, To Long Thanh, Nguyen Van Quang,Nguyen Quang Tuyen, Do Hong Anh (2019), "Isolation, serotypedetermination and toxicity test of Streptococcus suis strains

caused disease in pigs in Thai Nguyen province", Veterinary

Sciences and Techniques Journal, 26(2), pp 67 - 73.

3 Nguyen Manh Cuong, To Long Thanh, Nguyen Van Quang,Nguyen Quang Tuyen, Do Hong Anh (2018), "Results ofexperimental inactivated vaccine preventing pneumonia, athritis

diseases for pigs in Thai Nguyen province", Science and

Technology Journal of Agriculture and Rural Development,

November's volume, pp 130 - 135

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1 Urgency of the thesis

Pig production in Thai Nguyen province in recent years hasdeveloped rapidly quantity and improved quality, meeting thedemand of pig product consumption in the province and export-orientation, contributing to job creation and increasing income foranimal producers in the province, therefore it plays an important role

in the economic development of the province and has become a

leading livestock industry to be interested in developing Pig

production in Thai Nguyen is mostly small scale farms, so it facesmany difficulties, especially in the field of disease control, whichgreatly affects the efficiency of livestock production In addition toinfectious diseases that occur in pigs such as foot and mouth disease,swine fever, PRRS, pneumonia, arthritis in pigs caused by

Streptococcus suis (S suis) also occurs quite commonly leading to

economic loss for farmers The disease is caused by S suis in pigs

with pathological manifestations such as hemorrhage, pneumonia,arthritis, encephalitis resulting in death, especially in the period ofpost-weaning piglets, affecting weight gain, animal breed quality and

increasing the rate of breeding program.

S suis plays an important role in respiratory disease and

arthritis in pigs Investigation of Nguyen Thi Noi and Nguyen Ngoc

Nhien (1993) on the respiratory bacterial flora of 162 pigs withrespiratory infection accompanied with coughing showed thatStreptococcus accounted for 74.0% Investigation results of Do NgocThuy et al (2009b) from healthy pigs raised at pig farms, which were

taken to slaughter houses which expressed symptoms of pneumonia,

PRRRS or arthritis, encephalitis, S suis was isolated from all of them with different rates Among the S suis strains isolated, important and

common pathogenic serotypes 2 ,7 and 9 were found

S suis not only causes infection in pigs, it also causes

dangerous diseases in humans In Vietnam, many cases and deaths

have been recorded due to streptococcal infection According to

statistics of the general department of Preventive Medicine (Ministry

of Health) in 2017, in the country 171 cases of S suis in pigs were

recorded in the whole country, 14 of which died In particular, in june

-2018 in Thai Nguyen province, there were 3 cases suffering from S.

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suis infection (Phuong Nam, 2018) The affected people confirmed

that they had contact with sick pigs in feeding, slaughtering, eating

pork or blood pudding infected with Streptococcus suis.

Derived from the practical situation of production and foodsafety at present, aiming at better understanding of pneumonia and

arthritis in pigs associated with S suis, which is a scientific basis for

thesising measures of effective prevention and treatment, an urgentrequirement, making contribution to improvement of productionefficiency, increasing income for pig producers and protecting public

health, we carried out the project: "Investigating some biological

characteristics of Streptococcus suis causing pig diseases in Thai Nguyen province and manufacturing Autovaccine for prevention"

2 Objective of thesis

- Identifying some biological characteristics of S suis causing

pneumonia and arthritis in pigs raised in Thai Nguyen province

- Study on production of Autovaccine using S suis strains isolated for

prevention of pneumonia and arthritis in pigs and trials of effective

treatment regimens for pneumonia and arthritis caused by S suis,

making contribution to promoting pig production in Thai Nguyenprovince

3 The scientific and practical significance of the thesis

3.1 Scientific significance

- It is a systematic investigation of biological characteristics of S.

suis strains in pigs raised in Thai Nguyen.

- Investigation of manufacturing Autovaccine using S suis strains

isolated for effective prevention of pneumonia, arthritis of pigsraised in Thai Nguyen and recommendation of effective treatment

regimens of pneumonia, arthritis associated with S suis

- Supplement and enrichment of scientific data, using as reference in

teaching and thesising of pathogenic S suis in pigs.

3.2 Practical significance

- Trials of autovaccination of pigs raised in Thai Nguyen provincehas contributed to decreasing the rate of pigs suffering from

pneumonia, arthritis caused by S suis.

- Applying the treatment regimens for pneumonia, arthritis in pigsreaches high efficiency, contributing to increased income for animalproducers and sustainable development of pig husbandry in Thai

Nguyen province

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- The results of the thesis are a scientific basis to formulate effective

measures for prevention and treatment of diseases caused by S suis in

pigs

4 New contributions of the thesis:

- A systematic and complete investigation of S suis causing pig

diseases in Thai Nguyen province

- Autovaccine that has been successfully manufactured by isolated S.

suis strains can be effectively used for prevention pigs from

pneumonia arthritis; the treatment regimens of pigs can be applied in

practice of pig production in Thai Nguyen.

Chapter 1 REVIEW OF LITERATURE

Chapter 2 CONTENTS, MATERIALS AND METHODS

2.1 Objects and location

2.1.1 Objects of the thesis

- S suis isolated from pigs that infected by pneumonia and arthritis.

- S suis Autovaccine to prevent pigs from pneumonia and arthritis.

2.1.2 Study location

- Pig farms and farmer household in Thai Nguyen province which

were suspicious of being infected by S suis.

- Division of Microbiology, National Veterinary Diagnostic Center,Department of Animal Health

- Institute of Life Science, Thai Nguyen University

2.1.3 Study period -From 2015 to 2018.

2.2 Contents of the thesis.

2.2.1 Investigating the situation of pneumonia and arthritis in pigs raised in Thai Nguyen

- Identifying prevalence of affected pigs and motarlity of pigs withpneumonia and arthritis over the years in some districts and cities ofThai Nguyen province from 2015-2017

- Investigating the rate of prevalence and mortality of pigs caused bypneumonia, arthritis in pigs raised in Thai Nguyen from 2015-2017 at

different ages and seasons.

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2.2.2 Investigating some biological characteristics of isolated S suis strains

- Determining some biological and chemical characteristics of S.

suis strains isolated.

- Testing susceptibility of S suis strains isolated to some

antibiotics

- Serotyping isolated S suis strains

- Determining virulent factors of isolated S suis strains.

2.3.3 Investigating exprimental inactivated Autovaccine manufacture with alumminium adjuvant from isolated S suis strains

- Selecting S suis strains used for experimental Autovaccine

manufacture

- Investigating Autovaccine produced from selected S suis strains.

- Determining immune response of pigs to experimentalAutovaccine

2.2.4 Investigation of prevention and treatment of arthritis, pneumonia in pigs caused by S suis

- Experimenting Autovaccine produced from isolated S suis for

prevention of pneumonia and arthritis in pigs

- Using treatment regimens of pneumonia and arthritis in pig caused

by S suis.

2.3 Materials

- Samples were collected from lung, retropharyngeal fluid, synovialfluid, cerebrospinal fluid of sick or dead pigs with symptoms and

lesions suspicious of pneumonia or S suis infection such as fever,

anorexia , dyspnea, cough, swollen joints, nerve signs

- Healthy white mice (18-20g/mouse);

- Healthy piglets at the age of 5-6 weeks were not vaccinated withAutovaccine against pneumonia, arthritis caused by S suis

- Media and chemicals used according to the thesis procedure of thedivision of Microbiology of the Veterinary Institute and the National

Veterinary Diagnostic Center and the Animal Health Department.

- API 20 Strep kit system for determining biochemical characteristics

and nomenclature of S suis (BioMérieux, Marcy l’Etoile, France).

- Antibotic assay paper for testing antibiotic sustibility produced by Oxoid argency (UK)

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- Chemicals and bio-products used for agglutination reactions,

serology and PCR technique, IHA reaction

- Antibiotics: Cefanew-LA, Marflo-45%, Marphamox-LA and C-Namin produced by Marphavet Veterinary phar maceutical Company

Gluco-K Standard strains of S suis and corresponding standard sera were

provided by the National Veterinary Diagnostic Center, department

of Animal Health, used for reference of strains isolated using PCRand serology

- Common laboratory instruments, inoculation chamber, autoclaves,centrifuges, shaking machines, PCR technique used for investigation ofbacteria belonging to the Central Veterinary Diagnostic Center, AnimalHealth Department and Institute of Life Sciences of Thai NguyenUniversity

2.4 Methods of the thesis

2.4.1 Method of epidemiological thesis

Using methods of descriptive epidemiology and practicalepidemiology of Nguyen Nhu Thanh (2001)

2.4.2 Sampling method

- Samples were collected from retropharyngeal fluid, syncvial fluid:

Using a sterile cotton swab to place deeply in the throat, and theinflamed joint of sick pigs then place in cotton swab tube, stored at

40C and transferred to the laboratory for cultture and isolation of

bacteria.

- Lung samples from sick or dead pigs that expressed signs and

lesions suspicious of S suis infection were placed in sterile nylon

bags, stored at 40C and brought to the laboratory immediately forculture and isolation of bacteria

2.4.3 Methods of the thesis

- Methods of culture, isolation and testing of bacteria were carried

out according to the routine methods of Department of Microbiology,National Veterinary Institute, National Veterinary Diagnostic Centerand Department of Animal Health

- PCR technique was used to identify genes encoding some virulence

factors and S suis pathogenic serotypes according to Wisselink H.J.

et al (2002b), Silva L.M et al (2006), Do Ngoc Thuy and Le ThiMinh Hang (2009a)

- LD50 calculation method according to Reed L.J & Muench H (1938)

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- Determination of virulence of S suis isolated in experimental

animals of Sawade (1985)

- Determination of susceptibility to antibiotics of S suis isolated

from laborratory animals according to Bauer A.W (1966)

- Experimenting treatment regimens for pigs infected by pneumonia,arthritis based on the determination of susceptibility to antibiotics of

S suis bacteria strains to select highly sensitive antibiotic drugs,

being allowed in Vietnam

- The method of manufacturing Autovaccine is tested from isolated

S suis bacteria strains according to the process of Department of

Microbiology, Institute of Veterinary Medicine

- Testing sterile, safe and effective of Autovaccine tested according

to TCVN 8684: 2011 and QCVN 01: 187-2018

- Method of antibody titre determination in pigs injected withAutovaccine by Indirect Haemaglunation (IHA) according to the OIEvaccine evaluation procedure (2018)

Chapter 3 RESULTS AND DISCUSSION 3.1 The situation of pigs affected and died of pneumonia, arthritis from 2015 to 2017 in Thai Nguyen province

3.1.1 Prevalence of pigs affected and motarlity of pigs with pneumonia, arthritis from 2015-2017

Table 3.1: Prevalence of affected pigs and mortality rates of pigs associated with pneumonia and arthritis from 2015-2017

r of

pigs

Percen

t (%) Numbe

r of pigs

Percen

t (%) Numbe

r of pigs

Percen

t (%) Numbe

r of pigs

Percentag

e (%) Numbe

r of pigs

Percen

t (%) Numbe

r of pigs

Perce nt (%))

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investigation With pneumonia, in 2017 the herds of pigs accountedfor the highest morbidity and mortality rates (16.34% and 15.44%respectively), followed by 2016 (the rates was 13.71% and 12.03%respectively) and lowest was in 2015 (the rates were 12.88% and11.29% respectively) For arthritis, the highest prevalence andmortality rates were in 2017 (13.88% and 8.18% respectively),followed by 2016 (10.53% and 6.45% respectively) and the lowestwere in 2015 (9.50% and 5.73%) Similarly, the highest number ofpigs infected and died of pneumonia and arthritis was in 2017 (6.87%and 3.66%, respectively), followed by 2016 (5.02% and 2.89%respectively) and the lowest were in 2015 (3.97% and 2.61%

respectively).

In 2017, pneumonia and arthritis in pigs in Thai Nguyen werehigher morbidity and mortality prevalences than in the previous yearsbecause at that time the price of porkers was the lowest since the past

10 years so it had a great influence on the pig industry commercialpigs that were not able to be sold led to farms and family farmssuffer from heavy losses Animal producers almost neglectedmanagement and care of animals, sanitation, prevention andtreatment of animal diseases so a lot of diseases occured

3.1.2 Morbidity and mortality rates of pigs associated with pneumonia and arthritis in different seasons

Table 3.2: Morbidity and mortality rates of pigs associated with

pneumonia and arthritis different seasons

Seasons Number of investigate

d pigs

Pneumonia Arthritis Morbidity Mortality Morbidity Mortality Number

of pigs Percen t (%) Number of pigs Percen t (%)

Numbe

r of pigs

Percen t (%)

Number

of pigs

Percen t (%)

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were 9.06% and 8.10% respectively; for arthritis 12.16% and 7.39%compared with 9.52% and 5.78% respectively;.

The results of the thesis showed that pneumonia and arthritis inpigs in Thai Nguyen province often occured throughout the year, but

in the months of the Winter-Spring seasons, it is cold, and drizzly andhumid, adversely affecting the health of animals, creating favouritecondition for diseases occur, so both the diseases occured at a higher

by piglets and the lowest was in gilts and sows (15.35, 14.11) and5.31% respectively) For arthritis, the highest prevalence was in post-weaning pigs (16.02%), followed by piglets under 1 month of age(12.02%) and the lowest was in gilts and sows (3.04%)

Table 3.3: Morbidity and mortality rates of pigs infected by

pneumonia and arthritis at different ages

of pigs

Percent (%)

Number

of pigs

Percent (%)

Number

of pigs

Percent (%)

Number

of pigs

Percent (%)

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post-in pigs with streptococcal disease, most pigs were post-infected durpost-ing theperiod from 5 to 10 weeks of age, few pigs were infected over 32weeks of age or several hours after birth

Investigation results of survival of S.suis in some areas of Thua

Thien Hue province in spring-summer season of 2015 by Bui Thi

Hien et al (2016) also showed that the prevalence of S suis infection

in healthy pigs was 11.4%

3.2 Results of some biological characteristics of isolated S suis strains 3.2.1 Isolation of S suis bacteria from pigs with pneumonia and arthritis in Thai Nguyen

Table 3.4 showed that in 403 samples from pigs withpneumonia and arthritis at different ages, there were 212 samples that

S suis isolated accounting for 52.60%; The highest prevalence was

that of post-weaning pigs> 1 - 3 months of age (58.91%) and thelowest was that of piglets less than 1 month of age (45.79%) Our

results were in agreement with those of S suis isolated from

specimens of pigs infected with PRRS in Bac Giang by TruongQuang Hai and et al (2012), which was 51.67% and by Le Van Dung

et al (2013) , which was 55.10%, but higher than finding of NguyenThi Kim Lan and others (2016, 2017) when isolating bacteria causingpneumonia in pigs in Bac Ninh province from lungs andretropharyngeal lymph nodes of pigs found that the prevalence of S.suis was 38.67% and in pigs raised in Tuyen Quang province was

13.0% As a result, isolation of S suis in pigs in Thai Nguyen

showed that this bacterium had played an important role in

pneumonia and arthritis in pigs for the past years in Thai Nguyen Table 3.4: Results of S suis isolated from pigs at different age

suffering pneumonia and arthritis

Number of positive samples (+)

Perce nt (%)

Tota l (%)

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Results of investigating some biological and chemical

characteristics of S suis bacteria isolated from pigs's specimens with

pneumonia and arthritis in Thai Nguyen province found that all

strains had typical biological and chemical characteristics of S suis

bacteria as described by scientific documents

3.2.3 Results of investigating some biological and chemical characteristic of S suis bacteria isolated by API 20 Strep kit system

Results of investigating some biological and chemical

characteristics of S suis bacteria isolated by API 20 Strep kit system,

of which 20 reactions prepared in plastic tray produced by BioMrieuxcompany, including: VP, HIP ESC, PYRA, αGAL, βGUR, βGAL,PAL, LAP, ADH, RIB, ARA, MAN, SOR, LAC, TRE, INU, RAF,

AMD, GLYG The results showed that S suis strains isolated from

pigs in Thai Nguyen had all the typical biological and chemical

characteristics of S suis bacteria.

3.2.4 Result of antibiotic susceptibility test of isolated S suis strains

Table 3.5: Result of antibiotic susceptibility test of

isolated S suis strains

Orde

Numbe

r of strains tested

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Table 3.5 showed that S suis strains were highly susceptible to

ceftiofur (84.52%), florfenicol (81.54%), amoxicillin (80.35%),ampicillin (72.61%) and were resistant to several antibiotics such aserythromycin (82.73%), colistin (78.57%), neomycin (72.02%) andpenicillin G (58.33%) Our results were in agreement with those ofNguyen Thi Kim Lan and others (2017), when testing the

susceptibility of S suis strains isolated in pigs in Bac Ninh province

to some antibiotics, it showed high susceptibility to ceftiofur(81.82%), amoxicillin (79.55%), florfenicol (75.00%) and ampicillin(70.45%) The above results were the basis for us to select antibiotics

for treatment of streptococcal disease associated with S suis in pigs

in Thai Nguyen to reach high effectiveness

3.2.5 Results of serotyping isolated S.suis strains

Table 3.6 showed that number of S suis serotype 2 strains was

the highest (58.17%), followed by serotype 9 (16.34%), serotype 7(7.19%), the lowest was serotype 21 and 29 (1.96 and 2.61%

respectively); S suis serotype was not determinated in the rest 21 strains,

accounting for 13.72% For serotype 2, the highest was in post-weaningpigs (64.00%), followed by piglets <1 month old (58.97%) and the

lowest was in porkers (51.21%) Results of other S suis serotypes of S.

suis isolated in Thai Nguyen were not determinated.

Table 3.6:Results of serotyping isolated S suis strains

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r of positiv e strains (+)

Percen t (%)

Numbe

r of positiv e strains (+)

Percen t (%)

Numbe

r of positiv e strains (+)

Percen t (%)

Numbe

r of positiv e strains (+)

Percen t (%)

Numbe

r of positiv e strains (+)

Percen t (%)

Piglets

( ≤ 1 month

old)

39 23 58.97 2 5.13 6 15.39 0 0 1 2.56 7 17.94 Post weaned

piglets (>1- 3

months old) 50 32 64.00 3 6.00 7 14.00 1 2.00 1 2.00 6 12.00Porkers (>3 - 6

months old) 41 21 51.21 3 7.32 9 21.96 1 2.44 1 2.44 6 14.64Gilts, sows

( ≥ 6 months

old)

23 13 56.52 2 8.69 3 13.02 1 4.34 1 4.34 2 8.69

total 153 89 58.17 11 7.19 25 16.34 3 1.96 4 2.61 21 13.72

The results of our thesis were in agreement with those of some

authors such as Cu Huu Phu (2011), identified S suis serotype 2 strains

in pigs with PRRS at the rate of 58.33 % and Le Van Duong et al.(2013) when determinating serotype of S suis isolated from samples ofpigs with PRRS in Bac Giang, serotype 2 accounted for the highest rate(56.29%), followed by serotype 9 (17.03%) and the lowest was serotype

7 (5.18%)

3.2.6 The results of determination of gene encoding virulent factors of isolated S suis

The thesis results showed that among the genes encoding the

virulence factors, arcA gene carried by S suis strains accounted the highest percentage (75.5%), followed by mrp gene (71.1%), sly gene (62.2%) and epf gene (57.7%) 5types of gene combinations encoding

virulence factors were identified including: arc/sly, arcA/mrp, arcA/

epf, arcA/mrp/sly, arcA/mrp/sly and arcA/mrp/sly/epf in 45 S suis

strains studied Our thesis results were similar to those of some authorssuch as Do Ngoc Thuy and et al (2009) from healthy pigs and pigs withpneumonia symptoms, PRRS arthritis symptoms, or encephalitis from

which S suis were isolated at different rates In 211 S suis strains

studied 18 serotypes of which were identified, most commonly wereserotype 2, 7, 9 and 7 combinations of virulence genes Investigation of

Cu Huu Phu et al (2013) showed that serotype 2 strains carried the mostgene combinations which were scatteredly distributed in 5 combinations:

arcA, arcA/sly; arcA/mrp; arcA/mrp/sly and arcA/mrp/sly/ epf.

Results of PCR used for determining genes encoding virulence of

S suis strains isolated were shown in Figure 3.2

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